PROTECTIVE EFFECT OF STRAWBERRY LEAVES AGAINST NEPHROTOXICITY OF MALE RATS

Document Type : Original Article

Abstract

ABSTRACT
Nephrotoxicity refers to kidney dysfunction or kidney damage that is
associated with an overload of drugs or xenobiotic. Agents with recognized
nephrotoxicity include molds and fungi, cancer therapeutics such as
cisplatin. In this study determine of the protective effect of strawberry leaves
against nephrotoxicity of male rats was evaluated. Thirty five adult male
albino rats (Sprague-Dawley strain), weighing about (150±10g) were
divided randomly into seven groups (5rats of each) as follow; -ve and +ve
control groups which fed on basal diet. Groups 3 and 5 fed on basal diet
supplemented with 5% and 10% strawberry leaves powder (SLP),
respectively. Groups 4 and 6 were orally administered with 5% and 10%
strawberry leaves water extract (SLWE), respectively. Also group 7was
orally administered with 50ml of diluted silymarin /Kg body weight of rats.
At the end of the experiment 28 days +ve control and groups 3-7 were
intraperitoneally injected with a single dose of cisplatin 5mg/kg of body
weight for four days. Rats were weighed daily and feed intake and feed
efficiency ratios were calculated. At the end of the experimental period rats
were sacrificed and serum was collected for biochemical analysis. The result
showed that SLP and SLWE improing serum blood lipids and markers of
kidney function and liver function as compared to the positive control group,
decreased malondialhyde (MDA) level and increased the activity of
antioxidant enzymes, glutathione (GSH) in the nephrotoxic rats. The high
concentration of SLP and SLWE ameliorated histopathological and
biochemical alterations that caused by cisplatin administration. According to
above findings this research recommended that a strawberry leaf has a
potential to be used as a functional health food ingredient with beneficial
effects on kidney damage.

Keywords

Main Subjects


PROTECTIVE EFFECT OF STRAWBERRY LEAVES
AGAINST NEPHROTOXICITY OF MALE RATS
Nourelhouda M. Moustafa* ; Maysa M. El-Mallah
and Haggag M. Hamdy
Nutrition and Food Science Department, Faculty of Home Economics,
Helwan University, Cairo, Egypt
*E-mail - medoelmasrawy48@gmail.com
Key Words: strawberry, leaves, nephrotoxicity, kidney functions,
silymarin, rats
ABSTRACT
Nephrotoxicity refers to kidney dysfunction or kidney damage that is
associated with an overload of drugs or xenobiotic. Agents with recognized
nephrotoxicity include molds and fungi, cancer therapeutics such as
cisplatin. In this study determine of the protective effect of strawberry leaves
against nephrotoxicity of male rats was evaluated. Thirty five adult male
albino rats (Sprague-Dawley strain), weighing about (150±10g) were
divided randomly into seven groups (5rats of each) as follow; -ve and +ve
control groups which fed on basal diet. Groups 3 and 5 fed on basal diet
supplemented with 5% and 10% strawberry leaves powder (SLP),
respectively. Groups 4 and 6 were orally administered with 5% and 10%
strawberry leaves water extract (SLWE), respectively. Also group 7was
orally administered with 50ml of diluted silymarin /Kg body weight of rats.
At the end of the experiment 28 days +ve control and groups 3-7 were
intraperitoneally injected with a single dose of cisplatin 5mg/kg of body
weight for four days. Rats were weighed daily and feed intake and feed
efficiency ratios were calculated. At the end of the experimental period rats
were sacrificed and serum was collected for biochemical analysis. The result
showed that SLP and SLWE improing serum blood lipids and markers of
kidney function and liver function as compared to the positive control group,
decreased malondialhyde (MDA) level and increased the activity of
antioxidant enzymes, glutathione (GSH) in the nephrotoxic rats. The high
concentration of SLP and SLWE ameliorated histopathological and
biochemical alterations that caused by cisplatin administration. According to
above findings this research recommended that a strawberry leaf has a
potential to be used as a functional health food ingredient with beneficial
effects on kidney damage.
INTRODUCTION
Nephrotoxicity is the most common kidney problems occur when the
body is exposed to a drug or toxin. When kidney damage occurs, body
Egypt. J. of Appl. Sci., 36 (5-6) 2021 1-15
unable to get rid of excess urine and wastes from the body and blood
electrolytes. Konam and Yalamuri, (2014).
Cisplatin is a clinically advanced and highly effective anticancer drug
used in the treatment, it has only a limited use in clinical practice due to its
severe adverse effects, particularly nephrotoxicity; 20%–35% of patients
develop acute kidney injury (AKI) after Cisplatin administration. Recent in
vitro and in vivo studies show that numerous natural products (flavonoids,
saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific
antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate
the pathways associated with Cisplatin-induced kidney damage Fang et al .,
(2021) .
Herbal drugs are being in use for the management of human health
and for prevention as well as to cure human diseases since ancient
civilization. In recent days, the use of herbal drugs has been increased
significantly in various forms such as herbal formulations, dietary
supplements, and nutraceuticals in the global market. This growing demand
undoubtedly proves the therapeutic claims of herbal drugs as biomedicines
and/or functional foods Rudrapal and Chetia, (2021).
Strawberry tree water leaf extract showed high biocompatibility with
kidney tissue. It did not impair DNA integrity of renal cells and kidney
function, either in male or female rats Jurica et al., (2020).There is a long
list of other effects reported in folk medicine: as a diuretic, to strengthen
sight and dentition, to expel kidney stones and intestinal worms, to treat
anaemia and hepatitis, to strengthen the nervous, Strawberry leaves extract
can be considered a very promising phytochemical for treating the
neurotoxicity due to lead toxicity Issa et al., (2018).
Strawberry leaves as an abundant source of ellagitannins (ETs) can be
considered as a valuable biomaterial for industrial application such as food
ingredients, dietary supplements, pharmaceuticals and cosmetics .In
addition, strawberry leaves particularly rich in monomeric ETs have
potential application as a raw material for preparing the formulations for
controlling plant pathogens Karlińska et al .,(2021).
MATERIALS AND METHODS
Materials
Strawberry leaves of (Fragaria) in the rose family (Rosaceae) were
obtained from Agriculture Research Center, Cairo, Egypt. Chemical and
kits Cisplatin, Casein, cellulose, choline chloride, D-L methionine,
vitamins mixture and minerals mixture were purchased from Gomhoriya
2 Egypt. J. of Appl. Sci., 36 (5-6) 2021
Pharmaceutical Company, Cairo, Egypt. Starch, corn oil, and sucrose
were obtained from the Egyptian local market.
Methods:
Preparation of Leaves Water Extract:
Dried Strawberry leaves were grounded and submerged in distilled
water and allowed to soak overnight , 50 gm of leaves were added to
950ml water (5%) concentration ,100 gm of leaves were dissolved to
900 ml water (10%) concentration , then the water extract is administered
orally to rats .
- Induction of nephrotoxicity:
Intraperitoneally (i.p.) injected of male albino rats with a single
dose of Cisplatin 5mg/kg of body weight for four days Mansour et al.,
(2006).
Diet Composition and Experimental Animal Design:
The basal diet was formulated according to AIN-93M diet (Reeves
et al., 1993). Thirty five adult male albino rats (Sprague-Dawley strain),
weighing about (150±10g) were divided randomly into –ve and +ve
control groups were fed on basal diet throughout the experiment.Groups
3-7 were fed basal diet with 5 & 10% SLP; 5 & 10% SLWE; 50ml
silymarin, respictively.Positive and all tested groups (3-7) were i.p.
injected with a single dose of cisplatin 5mg/kg b.w of rats in the end of
the experiment(4weeks). After 2 days rats were fasted overnight before
scarifying and blood samples were collected from each rat and were
centrifuged at 3000 rpm for 15 min to obtain serum for biochemical
analysis.
Biological Evaluation: feed intake (FI), body weight gain (BWG%) and
feed efficiency ratio (FER) were determined according to Chapman et
al., (1959).
Serum Biochemical Analysis:
Serum total cholesterol (TC), triglyceride (TG), high density
lipoprotein cholesterol (HDL-C) were determined according to
Richmond, (1973); Wahlefeld, (1974) and Albers et al., (1983),
respectively. Regarding to serum low density lipoprotein cholesterol
(LDL-C) and very low density lipoprotein cholesterol (VLDL-C) were
calculated according to Friedewald et al., (1972). Serum level of
creatinine was determined colorimetrically using the method described
by Burtis and Ashwood, (1999) and Young, (2001). Serum albumin
level was determined as described by Young, (1995). Blood urea
nitrogen was determined as described by Schrier, (2008). Urea
concentration was determined according to method of Tabacco, (1979).
Egypt. J. of Appl. Sci., 36 (5-6) 2021 3
Serum uric acid was determined using the enzymatic colorimetric method
as described by Fossati et al., (1980). Aspartate aminotransaminase
(AST) and Alanine aminotransaminases (ALT) were determined
according to the method described by Young, (2001). Malondialdehyde
(MDA) and Glutathione peroxidase (GPx) were determined according to
Young, (2001).
Histopathological Examination: Specimens from the kidney were
dissected out, washed and placed in 10% neutral buffered for
histopathological according to Bancroft and Stevens, (1996).
Histopathological examination was done in Veterinary medicine, Cairo
University.
Statistical Analysis: Results were expressed as the mean standard error
± SE. Data were statistically analyzed for variance “ANOVA” test at P ≤
(0.05) using SPSS statistical software, version 20 was used for these
calculations (Armitage and Berry, 1987).
RESULTS AND DISCUSSION
Table (1) showed that strawberry leaves contained protein, fat, ash,
moisture, fiber and carbohydrate at 13.45, 5.38, 9.22, 3.80, 12.35 and
55.80%, respectively and ascorbic acid at 113.15 mg/100g. Results in Table
(2): revealed that strawberry leaves powder had more powerful in phenolic
and flavonoid compounds. The result revealed that SLP contained high
amount of benzoic acid, hydroxy benzoic acid and rutin with the value
718.13, 606.18 mg and 458.52 mg, respectively. As well as Table (3)
showed that antioxidant activities were recorded 94.37 % for SLP and 95.77
for SLWE. Similar results was obtained by Shalaby,(2018).Also results
showed that the high content of vitamin C was found in strawberry leaves
Oliveira et al., (2009). Another study by Zhong et al., (2016) confirmed
that the content of vitamin C in strawberry leaves, these results were in
agreement with Šic Žlabur et al., (2020). These results agree with K rlu d
et al., (2014) who detected those 21 different ellagitannins constituted the
largest group of compounds in the strawberry leaves. These results in the
same line with Buricova et al., (2011).
Table (1): Chemical composition and of strawberry leaves
Strawberry Leaves
Protein 13.45%
Fat 5.38%
ASH 9.22 %
Moisture 3.80%
Fiber 12.35%
Carb 55.80%
vitamin C Ascorbic acid 113.15 Mg/100g
4 Egypt. J. of Appl. Sci., 36 (5-6) 2021
Table (2): Polyphenolic Compounds Concentration of strawberry
leaves powder and its water extract
Polyphenolic Compounds Concentration of Polyphenolic Compounds(mg/kg)
Strawberry Leaves
Powder
Strawberry Leaves Water
Extract
3-Hydroxytyrosol - 241.23485
Catechol - 2.97130
Gallic acid 111.42381 56.23273
p-Hydroxybenzoic acid 606.18149 119.21654
Catchin 35.92478 10.00669
Chlorgenic 33.96632 1.35904
Vanillic acid 145.44196 15.03163
Caffeic acid 28.39657 7.78022
Syringic acid 44.40879 8.64853
p- Coumaric acid 46.09581 1.99560
Benzoic acid 718.13003 177.11228
Ferulic acid 23.96767 110.07631
Rutin 458.52870 146.52750
Ellagic 45.96542 32.07249
o- Coumaric acid 78.72518 45.25717
Resvertol 34.27319 60.59034
Cinnamic acid 34.04893 3.48184e-1
Quercetin 67.96691 17.85518
Rosemarinic -- 14.73611
Myricetin 15.16239 --
Quinol 43.53554 59.37174
Kampherol 2.08206 7.59562e-1
Total 2574.22556 1139.14579
Table (3): The antioxidant activity in strawberry leaves powder and
its water extract
Sample
%DPPH Radical-Scavenging Activity
0.05% 0.125% 0.2% 0.25% 0.5% 1%
strawberry leaves powder 74.65 86.20 - 94.37 - -
strawberry leaves water extract - - 73.52 - 87.61 95.77
Mean values in Table (4) showed the effect of strawberry leaves and
its water extract and silymarin (as a drug) on feed intake (FI), body weight
gain (BWG) and feed efficiency ratio (FER) of nephrotoxic rats. Feed intake
was decreased in positive control group compared to negative control group,
while treated groups with 5 and 10% of strawberry leaves (powder or its
water extract) or silymarin were close to negative control group. Cisplatin
caused significant decrease (P≤ 0.05) in BWG and FER for the positive
control group compared to the negative control group, while pretreated
groups with 5% and 10% strawberry leaves(powder or water extract ) or
silymarin were significantly increased in BWG compared to +ve group ,also
Egypt. J. of Appl. Sci., 36 (5-6) 2021 5
there were no significant differences in FER of treated groups compared to
the positive control group. Similar observation was obtained by Lin et al.,
(2018). Gastrointestinal tract disorders including vomiting ,nausea, stomach
distention and gastric stasis may result in decreased food intake Malik et al.,
(2006). Pre-treatment with strawberry leaves powder or extract showed
enhanced on feed intake, body weight gain and relative organ weight for
nephrotoxic pretreated rats. These results in the same line with Galal et al.,
(2014).While disagree with Duru, (2013) who found SL had no effect on
feed intake feed conversion ratio.
Table (4): Effect of dried strawberry leaves and its water extract on
Feed Intake (FI), Body Weight Gain (BWG) and Feed
Efficiency Ratio (FER) of Nephrotoxicity rats
Parameters
Groups
FI (g/d) BWG % FER
G1:-ve control 16.00 19.38±1.24a 0.120±0.080a
G2: +ve control 14.00 16.64±1.12c 0.041±0.003b
G3: 5% STLP 15.00 17.48±.60b 0.0412±0.0026b
G4: 5% STWE 15.00 17.52±1.23b 0.041±0.003b
G5: 10% STLP 15.40 17.70±0.77b 0.041±0.002b
G6: 10% STWE 15.50 18.00±0.75b 0.041±0.002b
G7:Silymarin 50 ml/k 15.40 17.92±0.43b 0.041±0.001b
*Mean values are expressed as means ± SE.
*Mean values at the same column with the same superscript letters are not statistically
significant at P≤ 0.05.
Data illustrated in Table (5) showed that cisplatin caused an increase
in serum levels of TC, TG, LDL-C and VLDL-C levels and decrease in
high density lipoprotein cholesterol (HDL-C) of +ve control group
compared to -ve control. On the other hand all groups that treated with
strawberry leaves powder or water extract were decreased significantly (P≤
0.05) in serum TC, TG , LDL-C and VLDL-C levels compared to the
positive control group, Regarding serum HDL-C level, results showed a
significant (P≤ 0.05) increase in serum HDL-C level of the pretreated groups
with strawberry leaves .Therefore the high concentration of strawberry
leaves water extract had the best effect on improving blood lipid profile,
which was close to the effect of silymarin. This research in agreement with
Abdel-Gayoum and Ahmida, (2017).In this study pretreatment of rats
with, strawberry leaves powder or extract that could be attributed to
enhanced lipid profile. In the same line ,hypolipidaemic action of may be
due to polyphenols and antioxidant present in strawberry leaves powder or
extract, the same effect of strawberry leaves extract on lipid profile was
confirmed by Forbes-Hernández et al., (2017) .Also agreement with El-
Hawary et al., (2021).
6 Egypt. J. of Appl. Sci., 36 (5-6) 2021
Table (5 ): Effect of dried strawberry leaves , its water extract and
silymarin on serum total cholesterol (TC), triglyceride
(TG), high density lipoprotein cholesterol (HDL-C), low
density lipoprotein cholesterol (LDL-C) and very low
density lipoprotein cholesterol (VLDL-C) of
nephrotoxicity rats
Parameters
Groups
TC TG HDL-C LDL-C VLDL-C
mg/dl
G1:-ve control 68.58±.65d 39.90±.56c 40.10±.51a 20.50±.50d 7.98±.11c
G2: +ve control 81.60±.68a 62.50±.92a 20.40±.51c 48.70±.37a 12.50±.18a
G3: 5% STLP 76.26±.74b 54.30±.37b 31.70±.54b 33.70±.54b 10.86±.07b
G4: 5% STWE 73.40±.40c 52.50±.71b 31.50±.55b 31.40±.60b 10.50±.14b
G5: 10% STLP 72.88±.96c 51.40±.53b 31.50±.50b 31.10±.51b 10.28±.11b
G6:10% STWE 73.60±.67c 50.50±.50b 33.70±.54b 29.80±.37c 10.10±.10b
G7:Silymarin 50
ml/kg b.wt
72.881±.09c 53.40±.98b 34.70±.37b 27.50±.81c 10.68±.11b
*Mean values are expressed as means ± SE.
*Mean values at the same column with the same superscript letters are not statistically
sig ifica t at P≤ 0.05.
As seen in Table (6), serum concentrations of creatinine, urea, blood
urea nitrogen (BUN), and uric acid were significantly (P≤ 0.05) elevated and
reduced in serum Albumin by cisplatin administration (positive control
group) compared with negative control group. It was observed significant
(P≤ 0.05) reduce in serum creatinine, urea, Blood urea nitrogen (Bun), uric
acid and elevated in serum Albumin for all groups treated with strawberry
leaves powder and its water extract or silymarin compared to positive
control group. Results indicated that strawberry leaves water extract at 10%
concentration had the best effect on enhancing kidney functions.
Sen et al., (2013) concluded that cisplatin administration produced a
significant increase in serum creatinine and BUN accompanied by
significant decrease in total proteins and albumin. These results were
confirmed by current study the results. Cis injected rats that received
strawberry leaves powder or extract had significant (P ≤ 0.05) lower levels
of urea, creatinine, blood urea nitrogen, uric acid and accompanied by
significant decrease in albumin compared to positive control. In the same
line Mohamed and Ashour,(2019) who confirmed that Both doses of
strawberry leaves extract caused the decrease in urea level, creatinine
level.Also Sato et al ., (2019) suggested that the strawberry leaf extract
may exert a potent hypouricemic effect. Natural phenolics, alkaloids,
coumarins and flavonoids such as hesperidin ,rutin, silymarin and
carotenoids were shown to ameliorate cis-mediated nephrotoxicity Sahu et
al., (2013). Moreover, Pattanayak et al., (2017) who reported that Ellagic
Acid binds to human serum albumin, the major transport protein in blood
serum that caused reduce serum albumin.
Egypt. J. of Appl. Sci., 36 (5-6) 2021 7
Table (6): Effect of dried strawberry leaves powder, its water extract
and silymarin on serum albumin creatinine, urea, blood
urea nitrogen (BUN), and uric acid
Parameters
Groups
Creatinine Urea Albumin BUN Uric acid
(mg/dl)
G1:-ve control 0.51±.01d 18.06 ±0.52c 4.30±.09a 8.10±0.18d 1.26±0.05c
G2:+vecontrol 0.99±.05a 44.00±1.00a 2.50±0.22c 17.62±0.53a 2.93±0.07a
G3: 5%STLP 0.69±.00b 22.00±1.00b 3.30±0.07b 10.30±0.44b 2.30±0.04b
G4: 5%STWE 0.65±.02c 21.30± 0.58b 3.74±0.07a 10.00±0.23b 2.18±0.012b
G5:10%STLP 0.69±.01b 21.90± 0.90b 3.86±0.07a 10.37±0.35b 1.97±0.016c
G6:10%STE 0.61±.02d 19.00± 0.45c 3.92±0.06a 8.90±0.16c 1.66±0.09d
G7:Silymarin50
ml/kg b.wt
0.58±.02d 21.40±1.03b 4.02±0.06a 9.17± 0.20c 1.89±0.05c
*Mean values are expressed as means ± SE.
*Mean values at the same column with the same superscript letters are not statistically
sig ifica t at P≤ 0.05.
Data revealed in Table (7) that serum concentrations of aspartate
aminotransferase (AST), alanine aminotransferase (ALT) were significantly
(P≤ 0.05) increased by cisplatin administration (+ve group) compared with -
ve control group, while pretreated rats with strawberry leaves (powder or
water extract) at doses 5% and 10% concentrations and silymarin 50 ml/kg
b.wt caused a significant decrease (P≤ 0.05) in the activity of AST , ALT
enzymes compared to the positive control group. Also it was observed that
strawberry leaves water extract at 5, 10% concentrations had the best effect
on improving liver functions. In the present study, induced with cis of rats
was confirmed by a significant elevation of AST and ALT. this agreement
with Mir et al., (2015).The results of this study showed that, nephrotoxic
rats pretreated with strawberry leaves powder or water extract effective
improvement in liver function and afforded a protection against cis toxicity.
These results were in accordance with those reported by Jurica et al.,
(2020) who showed that strawberry tree water leaf extract acceptable
biocompatibility with liver tissue both in male and female rats. As well as
Shalaby, (2018) who confirmed that strawberry leaves powder greatly
reduces high levels of serum ALT and AST.
Table (7): Effect of dried strawberry leaves, its water extract and
silymarin on aspartate aminotransferase (AST), alanin
aminotransferase (ALT) of nephrotoxicity rats
Parameters
Groups
AST ALT
U/L
G1: -ve control 7.00±0.45c 8.00±0.45cd
G2: +ve control 37.60±2.16a 26.00±1.00a
G3: 5% STLP 14.50±1.34b 14.50±0.57b
G4: : 5% STWE 8.80±0.58c 10.60±0.51c
G5: 10% STLP 11.00±0.71b 14.10±0.33b
G6: : 10% STWE 8.50±0.50c 9.70±0.44c
G7:Silymarin50ml/kg b.wt 11.30±0.86b 14.00±1.61b
*Mean values are expressed as means ± SE.
*Mean values at the same column with the same superscript letters are not statistically
sig ifica t at P≤ 0.05.
8 Egypt. J. of Appl. Sci., 36 (5-6) 2021
Results in Table (8) showed a significant decrease (P≤ 0.05) in serum
GPx activity of the +ver control group compared with the negative control
group. It was clear that, there was significant (P≤ 0.05) increase in serum
GPx activity for all treated groups with strawberry leaves or silymarin
compared to the positive control group. Concerning to serum
malondialdehyde (MDA) level, results showed that serum MDA level was
significantly increased (P≤ 0.05) in the +ve control group compared with the
-ve control group, whereas, all treated groups with strawberry leaves or
silymarin significantly decreased (P≤ 0.05) compared to the positive control
group. It was also observed that rats were administrated with 10%
strawberry leaves water extract considered the best group for increasing the
serum GPx and reducing serum MDA levels. Lipid peroxidation closely
related to Cis-induced toxicity Somani,( 2000). The result of the present
study supported the findings of the previous studies as there was an increase
in serum lipid peroxidation (MDA) , and decrease in GPx. The observed
increase in MDA in the current study could be because cisplatin induced
formation of free radicals and also through exhaustion of antioxidants
leading to oxidative stress Verma et al., (2016).In this study, it was found
that strawberry leaves Provides great protection against nephrotoxicity CIS
effects. The strawberry leaves were too able to significantly reduce MDA
production and increase GSH levels in the blood Similarly.These results
strongly support that Strawberry leaves are strong antioxidant, antiinflammatory
and protective effects against cis-induced toxicity. Ibrahim
and Abd El-Maksoud, (2019) suggested that strawberry leaf extract might
be used as an antioxidant, ant -inflammatory ,and anti -apoptosis to improve
brain damage caused by diabetes. These result agree with Zhang et al .,
(2020) .The presence of Ellagic acid in strawberry leaves could have been
the cause for the observed protection of kidney from Cisplatin induced
toxicity Aslan et al., (2020).
Table (8): Effect of dried strawberry leaves, its water extract
silymarin on serum glutathione peroxidase (GSH) and
malondialdehyde (MDA) of nephrotoxicity rats
Parameters
Groups
GSH
(μmol/dL)
MDA
(μmol/dL)
G1: -ve control 19.66± .38a 3.44±.16d
G2: +ve control 10.50±.50d 7.67±.54a
G3: 5% SLP 14.80± .29d 5.01±.17b
G4: 5% STWE 16.06±.12c 3.82±.19d
G5: 10% STLP 17.02±.17b 5.26±.16b
G6: 10% STLWE 17.92±.15b 3.65±.19d
G6: Silymarin 15.84±.29d 4.18±.18c
*Mean values are expressed as means ± SE.
*Mean values at the same column with the same superscript letters are not statistically
significant at P≤ 0.05.
The histopathological examinations of kidney are shown the effect of
strawberry leaves powder or extract from Photos 1 - 7. All histopathological
Egypt. J. of Appl. Sci., 36 (5-6) 2021 9
findigs were in harmony with serum biochemical parameters. Results of the
histological examination of previous studies demonstrated changes in kidney
structure due to Cis treatment. In several studies, glomerular and tubular
modifications were found to be a result of Cis Ravindra et al., (2010). In
this study, pretreated with strawberry leaves reduced the Severity of cisinduced
renal histological changes. These histological findings agreed with
the study of Zhang et al., (2020).
The histopathological examinations of kidney
Photo (1)
Photo(2)
Photo(2)
Photo (4) Photo (5) Photo (6)
Photo(7)
Photo
(1)
Kidney of negative control group (1) rats showing that in normal kidney,
the tubules are relatively uniform parallel arrangement and No
leukocytes are present. (H & E X 400)
Photo
(2)
positive control group (2), the cisplatin-injected kidneys showed marked
injury with sloughing of tubular epithelial cells, loss of brush border, and
dilation of tubule (H & E X 400)
Photo
(3)
kidney of rat from group (3), fed on strawberry leaves powder 5%
Showing normal appearance of tubules with loss of some brush border in
so tubules. (H & E X 400)
Photo
(4)
kidney of rat from group (4), oral administrated of strawberry leaves
extract 5% Showing normal appearance of kidney structure with
infiltration of some inflammatory cells (H & E X 400)
Photo
(5)
kidney of rat from group (5), fed on strawberry leaves powder 10% )
showing normal appearance of proximal convoluted tubule with some
evidence of blood (H & E X 400)
Photo
(6)
kidney of rat from group (6), showed Normal appearance oral
administrated of strawberry leaves extract at 10%(H & E X 400)
Photo
(7)
kidney of rat from group (7), oral administrated of Silymarin as drug
showed Normal appearance (H & E X 400)
10 Egypt. J. of Appl. Sci., 36 (5-6) 2021
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technique, Churchill, Livingston, Eden burgh, London,
Melhourne and New York.
Buricova, L. ; M. Andjelkovic ; A. Cermakova ; Z. Reblova ; O.
Jurcek,; E. Kolehmainen, and F. Kvasnicka (2011):
Antioxidant capacities and antioxidants of strawberry,
blackberry and raspberry leaves. Czech Journal of Food
Sciences, 29 (2): 181-189..
Burtis, C. and E. Ashwood (1999): Tietz textbook of clinical chemistry.
3rd ed. Philadelphia: W.B. Saunders, 1999: 1840, 1841, 1844,
1845; 1799; 1834-5 Textbook of Clinical Chemistry, 3rd ed
AACC.
Chapman, G. ; R. Castillo and A. Campbell (1959): Evaluation of
protein in foods: 1. A method for the determination of protein
efficiency ratios. Canadian Journal of Biochemistry and
Physiology, 37(5): 679-686.
Duru, M. (2013): Effects of dietary strawberry (Fragaria x ananassa
Duch.) leaf powder on egg yield, quality and egg yolk
cholesterol in laying hens. J Food Agric Environ, 11: 477-480.
El-Hawary, S. ; R. Mohammed ; M. El-Din ; H. Hassan ; Z. Ali ; M.
Rateb and R. Abdelmohsen, (2021): Comparative
phytochemical analysis of five Egyptian strawberry cultivars
(Fragaria× ananassa Duch.) and antidiabetic potential of Festival
and Red Merlin cultivars. RSC Advances, 11(27): 16755-16767.
Egypt. J. of Appl. Sci., 36 (5-6) 2021 11
Fang, Y. ; Y. Lou ; Q. Zhou ; C. Wang ; J. Yang and J. Weng (2021)
: Natural products: potential treatments for cisplatin-induced
nephrotoxicity. Acta Pharmacologica Sinica, 1-19.
Forbes-Hernández, Y. ; M. Gasparrini ; S. Afrin ; D. Cianciosi ; M.
González-Paramás ; C. Santos-Buelga and S. Bompadre
(2017): Strawberry (cv. Romina) methanolic extract and
anthocyanin-enriched fraction improve lipid profile and
antioxidant status in HepG2 cells. International journal of
molecular sciences, 18(6): 1149.
Fossati, F. and L. Principe (1982): Plasma triglycerides determined
colorimetrically with an enzyme that produces hydrogen
peroxide. Clin. Chem., 28(10):2077-2080.
Friedewald, T. ; I. Leve and S. Fredrickson (1972): Graw Hill Book
Company (U.K.) Limited
Galal, F. ; A. El Menniawy ; H. Abo-Fadel and A. Khir (2014): Some
nutritional studies on using strawberry (Fragaria ananas) vine
as hay in rabbit ration. Journal of Animal and Poultry
Production, 5(12): 635-647.
Abd El-Maksoud, M.A. and S. Ibrahim (2019): Strawberry (Fragaria x
ananassa) leaf extract reduces brain damage in diabetic male
rats. Egypt. J. Exp. Biol. (Zool.), 15(1): 39 – 43
Issa, I. ; A. Abbas and I. Abdel-Gawad (2018): Potential impact of
strawberry leaves extract on neurotoxicity in rats . International
Journal of Innovative Science and Research Technology,2456-2165
Jurica, K. ; V. Be ković ; S. Sikirić ; I. Brčić Karačo ji a d N.
Kopjar (2020): The effects of strawberry tree (Arbutus unedo
L.) water leaf extract and arbutin upon kidney function and
primary DNA damage in renal cells of rats. Nat Prod Res., 2020
34(16):2354-2357
Karlińska, E. ; A. Masny ; M. Cieślak ; J. Macierzyński ; Ł. Pecio ;
A. Stochmal and M. Kosmala (2021) : Ellagitannins in roots,
leaves, and fruits of strawberry vary with developmental stage
and cultivar. Scientia Horticulturae, 275: 109665.
K rlu d, A. ; P. Salminen ; P. Koskinen ; R. Ahern ; M. Karonen ;
K. Tiilikkala and O. Karjalainen (2014): Polyphenols in
strawberry (Fragaria× ananassa) leaves induced by plant
activators. Journal of Agricultural and Food Chemistry, 62(20):
4592-4600.
12 Egypt. J. of Appl. Sci., 36 (5-6) 2021
Konam, B. and C. Yalamuri (2014): A review on nephroprotective
activity of herbal plants. J Compr Phar; 1(4):95-107.
Lin, M. ; J. Ko ; T. Liu ; P. Chao and C. Ou (2018): Protective Effect
of D-Methionine on Body Weight Loss, Anorexia,
and Nephrotoxicity in Cisplatin-Induced Chronic Toxicity in
Rats 17(3):813 –824.
Malik, N. ; G. Moore ; G. Smith ; Y. Liu ; G. Sanger and P. Andrews
(2006): Behavioral and hypothalamic molecular effects of the
anti-cancer agent cisplatin in the rat: a model of chemotherapy
related malaise? Pharmacol Biochem Behav; 83:20.
Mansour, H. ; F. Hafez and M. Fahmy (2006): Silymarin modulates
cisplatin-induced oxidative stress and hepatotoxicity in
rats. BMB Reports, 39(6): 656-661.
Mir, M. ; M. Arab ; M. Shahraki ; M. Mashhadi ; M. Salar ; F. Aval
and M. Karimfar (2015): Toxic Effects of Cisplatin on
Hepatocytes and Liver Enzymes of Rats. Journal Of Iranian
Anatomical Sciences, 12(4): 171 - 175.
Mohamed, E. and E. Ashour (2019): Influence of ethanolic extract of
strawberry leaves for abrogating bromate hazards in male
rats. The Journal of Basic and Applied Zoology, 80(1): 1-6.
Oliveira, I. ; V. Coelho ; R. Baltasar ; J. Pereira and P. Baptista
(2009): Scavenging capacity of strawberry tree (Arbutus unedo
L.) leaves on free radicals. Food and Chemical
Toxicology, 47(7): 1507-1511.
Pattanayak, R. ; P. Basak ; S. Sen and M. Bhattacharyya (2017): An
insight to the binding of ellagic acid with human serum albumin
using spectroscopic and isothermal calorimetry studies.
Biochemistry and Biophysics Reports ,10: 88–93 peroxide. Clin.
Chem., 28(10):2077-2080.
Ravindra, P. ; A. Bhiwgade ; S. Kulkarni ; P. Rataboli and C.Y.
Dhume (2010) : Cisplatin induced histological changes in renal
tissue of rat. Journal of Cell and Animal Biology, 4(7): 108-111.
Reeves, G.; H. Nielsen and C. Fahmy (1993): AIN-93 purified diets for
laboratory rodents: final reporte of committee of reformulation
of the AIN-76 A rodent diet. J. Nutr.,123: 1939-51.
Richmond, N. (1973): Colorimetric determination of total cholesterol
and high density lipoprotein cholesterol (HDL-c). Clin. Chem.,
19: 1350-1356.
Egypt. J. of Appl. Sci., 36 (5-6) 2021 13
Rudrapal, M. and D. Chetia (2021): Herbal Drugs: Efficacy, Toxicity,
and Safety Issues. In Evidence Based Validation of Traditional
Medicines:537-553.
Sahu, B. ; M. Kuncha ; G. Sindhura and R. Sistla (2013): Hesperidin
attenuates cisplatin-induced acute renal injury by decreasing
oxidative stress, inflammation and DNA damage .
Phytomedicine; 20: 453-460.
Sato, T. ; Y. Ikeya ; I. Adachi ; K. Yagasaki ; I. Nihei and N. Itoh
(2019): Extraction of strawberry leaves with supercritical
carbon dioxide and entrainers: Antioxidant capacity, total
phenolic content, and inhibitory effect on uric acid production of
the extract. Food and Bioproducts Processing, 117: 160-169.
Schrier, W. (2008): Blood urea nitrogen and serum creatinine: not
married in heart failure. Circulation: Heart Failure, 1(1): 2-5.
Sen, S. ; D. Biplab ; N. Devanna and R. Chakraborty (2013) :isplatininduced
nephrotoxicity in mice: protective role of Leea asiatica
leaves. Renal Failure, 35 (10): 1412-1417.
Shalaby, Hanan S. (2018): Impact of Strawberry (Fragaria x ananassa)
Leaves Powder on Induced Diabetic Rats. Scientific Journal of
the Faculty of Specific Education,14 (1)1-2
Šic Žlabur, J. ; Bogda ović, S., Voća, S. a d Ske drović Babojelić,
M. (2020): Biological potential of fruit and leaves of strawberry
tree (Arbutus unedo L.) from Croatia. Molecules, 25(21), 5102.
Somani, M. ; K. Husain ; C. Whitworth ; L. Trammell ; M. Malafa
and P. Rybak (2000) :Dose‐dependent protection by lipoic
acid against cisplatin‐induced nephrotoxicity in rats: antioxidant
defense system. Pharmacology & toxicology, 86(5): 234-241.
Tabacco, A. (1979): Quntitative enzymatic colorimetric determination
of blood urea nitrogen in serum or plasma. Clin. Chem, 25:336.
Verma, P. ; R. Raina ; M. Sultana ; M. Singh and P. Kumar (2016):
Total antioxidant and oxidant status of plasma and renal tissue of
cisplatin-induced nephrotoxic rats: protection by floral extracts of
Calendula officinal is Linn. Ren Fail; 38(1): 142–150.
Wahlefeld, A. (1974): Methods of Enzymatic Analysis. Academic Press,
Chapter, 5: 1831-1835.
Young, Donald S. (1995): Effect of drugs on clinical lab Tests, 4 th ed.
Washington (D.C.) : AACC press
Yousef, I. ; A. Saad and K. El-Shennawy (2009):Protective effect of
grape seed proanthocyanidin extract against oxidative stress
induced by cisplatin in rats. Food and Chemical
Toxicology, 47(6): 1176-1183.
Young, D. (2001): Effect of disease on clinical lab Tests, 4thed. AACC
press. Clin. Chem., 19: 1350-1356. colorimetrically with an
14 Egypt. J. of Appl. Sci., 36 (5-6) 2021
enzyme that produces hydrogen determination of high density
lipoprotein cholesterol, Selected Methods. Clin. Chem., 10: 91-99.
Zhang, L. ; Q. Ma and Y. Zhou (2020): Strawberry Leaf Extract
Treatment Alleviates Cognitive Impairment by Activating
Nrf2/HO-1 Signaling in Rats With Streptozotocin-Induced
Diabetes. Frontiers in Aging Neuroscience, 12.
Zhong, F. ; L. Mazzoni ; F. Balducci ; L. Di Vittori ; F. Capocasa ; F.
Giampieri and B. Mezzetti (2016): Evaluation of vitamin C
content in fruit and leaves of different strawberry genotypes.
In VIII International Strawberry Symposium, 1156: 371-77.
التأثير الوقائي لأو ا رق الف ا رولة ضد تسمم نفرونات الکمى فى ذکور الفئ ا رن
نو ا رلهدى محمد مصطفى , مايسه محمد الشحات , محمد حمدي حجاج
قسم التغذية وعموم الأطعمة - کمية الاقتصاد المنزلي - جامعة حموان
يشير التسمم الکموى الى اختلال وظيفى أوتمف الکمى المرتبط بجرعة عالية من
الادوية او الکائنات الحية الغريبه ومن اهم مسببات التسمم الکموى العفن ,الفطريات وعلاجات
السرطان مثل السيسبلاتين . کان هدف هذة الد ا رسة معرفة التاثير الوقائى لأو ا رق الف ا رولة ضد
تسمم نفرونات الکمى فى ذکور الفئ ا رن . حيث أجريت الد ا رسة عمي خمسة وثلاثون فأ ا ر من نوع
10 جم( . تم تقسيم الفئ ا رن الي سبع مجموعات) 5 فأر لکل ± الالبينو, تت ا روح أو ا زنهم من ) 150
منهم(. مجموعة ضابطه سالبه تم تغذيتهم عمي الغذاء الأساسي طوال فترة التجربة) 4
اسابيع(.المجموعة الضابطه الموجبه تم تغذيتهم عمي الغذاء الآساسي و حقنهم تحت الجمد
بجرعة واحدة من سيسبلاتين 5 ممجم / کجم من وزن الجسم في اخر التجربه لإحداث تمف حاد
٪ 7 تم تغذيتهم عمي الغذاء الأساسي مضاف الية 5 و 10 - في الکمى. المجموعات من 3
مسحوق أو ا رق الف ا رولة و 5 و 10 ٪ المستخمص المائى لأو ا رق الف ا رولة و 50 مل من سيميمارين
فموي ا / کجم من وزن الجسم لمفئ ا رن عمي التوالي. وبعد يومين من الحقن بالسيسبلاتن تم تشريح
الفئ ا رن والحصول عمى عينات الدم لاج ا رء التحاليل البيوکيميائية واج ا رء الفحوص التشريحية. کما
تم وزن الفئ ا رن و حساب نسب زيادة الوزن وکفاءة التغذية . ولقد أظهرت النتائج ان مسحوق
او ا رق الف ا رولة والمستخمص المائى حسنوا من نسبة الدهون في الدم و وظائف الکمى وکذا وظائف
وزيادة نشاط MDA الکبد مقارنة بالمجموعة الضابطة الإيجابية , کما لوحظ انخفاض مستوى
إلى تحسين SLWE و SLP أدى الترکيز العالي ل .GSH , أنزيمات مضادات الأکسدة
التغي ا رت النسيجية والکيميائية الحيوية التي يسببها السيسبلاتين. لذلک يمکن التوصية باستخدام
أو ا رق الف ا رولة کمکون غذائي صحي وظيفي له آثار مفيدة عمى الوقايه من تمف الکمى.
کممات مفتاحية: مسحوق أو ا رق الف ا رولة , خلاصة ماء أو ا رق الف ا رولة , وظائف الکمي , فئ ا رن
التجارب , تسمم نفرونات الکمي
Egypt. J. of Appl. Sci., 36 (5-6) 2021 15

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and renal cortical lipids and electrolytes in rabbits with cisplatininduced
nephrotoxicity. Turkish Journal of Medical
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Aslan, A. ; O. Gok ; S. Beyaz ; A. Ağca ; O. Erman and A. Zerek
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tetrachloride induced rats. Molecular Biology Reports, 47(10):
7959-7970.
Bancroft, J. and A. Stevens (1996): Theory and practice of histological
technique, Churchill, Livingston, Eden burgh, London,
Melhourne and New York.
Buricova, L. ; M. Andjelkovic ; A. Cermakova ; Z. Reblova ; O.
Jurcek,; E. Kolehmainen, and F. Kvasnicka (2011):
Antioxidant capacities and antioxidants of strawberry,
blackberry and raspberry leaves. Czech Journal of Food
Sciences, 29 (2): 181-189..
Burtis, C. and E. Ashwood (1999): Tietz textbook of clinical chemistry.
3rd ed. Philadelphia: W.B. Saunders, 1999: 1840, 1841, 1844,
1845; 1799; 1834-5 Textbook of Clinical Chemistry, 3rd ed
AACC.
Chapman, G. ; R. Castillo and A. Campbell (1959): Evaluation of
protein in foods: 1. A method for the determination of protein
efficiency ratios. Canadian Journal of Biochemistry and
Physiology, 37(5): 679-686.
Duru, M. (2013): Effects of dietary strawberry (Fragaria x ananassa
Duch.) leaf powder on egg yield, quality and egg yolk
cholesterol in laying hens. J Food Agric Environ, 11: 477-480.
El-Hawary, S. ; R. Mohammed ; M. El-Din ; H. Hassan ; Z. Ali ; M.
Rateb and R. Abdelmohsen, (2021): Comparative
phytochemical analysis of five Egyptian strawberry cultivars
(Fragaria× ananassa Duch.) and antidiabetic potential of Festival
and Red Merlin cultivars. RSC Advances, 11(27): 16755-16767.
Egypt. J. of Appl. Sci., 36 (5-6) 2021 11
Fang, Y. ; Y. Lou ; Q. Zhou ; C. Wang ; J. Yang and J. Weng (2021)
: Natural products: potential treatments for cisplatin-induced
nephrotoxicity. Acta Pharmacologica Sinica, 1-19.
Forbes-Hernández, Y. ; M. Gasparrini ; S. Afrin ; D. Cianciosi ; M.
González-Paramás ; C. Santos-Buelga and S. Bompadre
(2017): Strawberry (cv. Romina) methanolic extract and
anthocyanin-enriched fraction improve lipid profile and
antioxidant status in HepG2 cells. International journal of
molecular sciences, 18(6): 1149.
Fossati, F. and L. Principe (1982): Plasma triglycerides determined
colorimetrically with an enzyme that produces hydrogen
peroxide. Clin. Chem., 28(10):2077-2080.
Friedewald, T. ; I. Leve and S. Fredrickson (1972): Graw Hill Book
Company (U.K.) Limited
Galal, F. ; A. El Menniawy ; H. Abo-Fadel and A. Khir (2014): Some
nutritional studies on using strawberry (Fragaria ananas) vine
as hay in rabbit ration. Journal of Animal and Poultry
Production, 5(12): 635-647.
Abd El-Maksoud, M.A. and S. Ibrahim (2019): Strawberry (Fragaria x
ananassa) leaf extract reduces brain damage in diabetic male
rats. Egypt. J. Exp. Biol. (Zool.), 15(1): 39 – 43
Issa, I. ; A. Abbas and I. Abdel-Gawad (2018): Potential impact of
strawberry leaves extract on neurotoxicity in rats . International
Journal of Innovative Science and Research Technology,2456-2165
Jurica, K. ; V. Be ković ; S. Sikirić ; I. Brčić Karačo ji a d N.
Kopjar (2020): The effects of strawberry tree (Arbutus unedo
L.) water leaf extract and arbutin upon kidney function and
primary DNA damage in renal cells of rats. Nat Prod Res., 2020
34(16):2354-2357
Karlińska, E. ; A. Masny ; M. Cieślak ; J. Macierzyński ; Ł. Pecio ;
A. Stochmal and M. Kosmala (2021) : Ellagitannins in roots,
leaves, and fruits of strawberry vary with developmental stage
and cultivar. Scientia Horticulturae, 275: 109665.
K rlu d, A. ; P. Salminen ; P. Koskinen ; R. Ahern ; M. Karonen ;
K. Tiilikkala and O. Karjalainen (2014): Polyphenols in
strawberry (Fragaria× ananassa) leaves induced by plant
activators. Journal of Agricultural and Food Chemistry, 62(20):
4592-4600.
12 Egypt. J. of Appl. Sci., 36 (5-6) 2021
Konam, B. and C. Yalamuri (2014): A review on nephroprotective
activity of herbal plants. J Compr Phar; 1(4):95-107.
Lin, M. ; J. Ko ; T. Liu ; P. Chao and C. Ou (2018): Protective Effect
of D-Methionine on Body Weight Loss, Anorexia,
and Nephrotoxicity in Cisplatin-Induced Chronic Toxicity in
Rats 17(3):813 –824.
Malik, N. ; G. Moore ; G. Smith ; Y. Liu ; G. Sanger and P. Andrews
(2006): Behavioral and hypothalamic molecular effects of the
anti-cancer agent cisplatin in the rat: a model of chemotherapy
related malaise? Pharmacol Biochem Behav; 83:20.
Mansour, H. ; F. Hafez and M. Fahmy (2006): Silymarin modulates
cisplatin-induced oxidative stress and hepatotoxicity in
rats. BMB Reports, 39(6): 656-661.
Mir, M. ; M. Arab ; M. Shahraki ; M. Mashhadi ; M. Salar ; F. Aval
and M. Karimfar (2015): Toxic Effects of Cisplatin on
Hepatocytes and Liver Enzymes of Rats. Journal Of Iranian
Anatomical Sciences, 12(4): 171 - 175.
Mohamed, E. and E. Ashour (2019): Influence of ethanolic extract of
strawberry leaves for abrogating bromate hazards in male
rats. The Journal of Basic and Applied Zoology, 80(1): 1-6.
Oliveira, I. ; V. Coelho ; R. Baltasar ; J. Pereira and P. Baptista
(2009): Scavenging capacity of strawberry tree (Arbutus unedo
L.) leaves on free radicals. Food and Chemical
Toxicology, 47(7): 1507-1511.
Pattanayak, R. ; P. Basak ; S. Sen and M. Bhattacharyya (2017): An
insight to the binding of ellagic acid with human serum albumin
using spectroscopic and isothermal calorimetry studies.
Biochemistry and Biophysics Reports ,10: 88–93 peroxide. Clin.
Chem., 28(10):2077-2080.
Ravindra, P. ; A. Bhiwgade ; S. Kulkarni ; P. Rataboli and C.Y.
Dhume (2010) : Cisplatin induced histological changes in renal
tissue of rat. Journal of Cell and Animal Biology, 4(7): 108-111.
Reeves, G.; H. Nielsen and C. Fahmy (1993): AIN-93 purified diets for
laboratory rodents: final reporte of committee of reformulation
of the AIN-76 A rodent diet. J. Nutr.,123: 1939-51.
Richmond, N. (1973): Colorimetric determination of total cholesterol
and high density lipoprotein cholesterol (HDL-c). Clin. Chem.,
19: 1350-1356.
Egypt. J. of Appl. Sci., 36 (5-6) 2021 13
Rudrapal, M. and D. Chetia (2021): Herbal Drugs: Efficacy, Toxicity,
and Safety Issues. In Evidence Based Validation of Traditional
Medicines:537-553.
Sahu, B. ; M. Kuncha ; G. Sindhura and R. Sistla (2013): Hesperidin
attenuates cisplatin-induced acute renal injury by decreasing
oxidative stress, inflammation and DNA damage .
Phytomedicine; 20: 453-460.
Sato, T. ; Y. Ikeya ; I. Adachi ; K. Yagasaki ; I. Nihei and N. Itoh
(2019): Extraction of strawberry leaves with supercritical
carbon dioxide and entrainers: Antioxidant capacity, total
phenolic content, and inhibitory effect on uric acid production of
the extract. Food and Bioproducts Processing, 117: 160-169.
Schrier, W. (2008): Blood urea nitrogen and serum creatinine: not
married in heart failure. Circulation: Heart Failure, 1(1): 2-5.
Sen, S. ; D. Biplab ; N. Devanna and R. Chakraborty (2013) :isplatininduced
nephrotoxicity in mice: protective role of Leea asiatica
leaves. Renal Failure, 35 (10): 1412-1417.
Shalaby, Hanan S. (2018): Impact of Strawberry (Fragaria x ananassa)
Leaves Powder on Induced Diabetic Rats. Scientific Journal of
the Faculty of Specific Education,14 (1)1-2
Šic Žlabur, J. ; Bogda ović, S., Voća, S. a d Ske drović Babojelić,
M. (2020): Biological potential of fruit and leaves of strawberry
tree (Arbutus unedo L.) from Croatia. Molecules, 25(21), 5102.
Somani, M. ; K. Husain ; C. Whitworth ; L. Trammell ; M. Malafa
and P. Rybak (2000) :Dose‐dependent protection by lipoic
acid against cisplatin‐induced nephrotoxicity in rats: antioxidant
defense system. Pharmacology & toxicology, 86(5): 234-241.
Tabacco, A. (1979): Quntitative enzymatic colorimetric determination
of blood urea nitrogen in serum or plasma. Clin. Chem, 25:336.
Verma, P. ; R. Raina ; M. Sultana ; M. Singh and P. Kumar (2016):
Total antioxidant and oxidant status of plasma and renal tissue of
cisplatin-induced nephrotoxic rats: protection by floral extracts of
Calendula officinal is Linn. Ren Fail; 38(1): 142–150.
Wahlefeld, A. (1974): Methods of Enzymatic Analysis. Academic Press,
Chapter, 5: 1831-1835.
Young, Donald S. (1995): Effect of drugs on clinical lab Tests, 4 th ed.
Washington (D.C.) : AACC press
Yousef, I. ; A. Saad and K. El-Shennawy (2009):Protective effect of
grape seed proanthocyanidin extract against oxidative stress
induced by cisplatin in rats. Food and Chemical
Toxicology, 47(6): 1176-1183.
Young, D. (2001): Effect of disease on clinical lab Tests, 4thed. AACC
press. Clin. Chem., 19: 1350-1356. colorimetrically with an
14 Egypt. J. of Appl. Sci., 36 (5-6) 2021
enzyme that produces hydrogen determination of high density
lipoprotein cholesterol, Selected Methods. Clin. Chem., 10: 91-99.
Zhang, L. ; Q. Ma and Y. Zhou (2020): Strawberry Leaf Extract
Treatment Alleviates Cognitive Impairment by Activating
Nrf2/HO-1 Signaling in Rats With Streptozotocin-Induced
Diabetes. Frontiers in Aging Neuroscience, 12.
Zhong, F. ; L. Mazzoni ; F. Balducci ; L. Di Vittori ; F. Capocasa ; F.
Giampieri and B. Mezzetti (2016): Evaluation of vitamin C
content in fruit and leaves of different strawberry genotypesIn VIII International Strawberry Symposium, 1156: 371-77.