Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.

BACKGROUND: Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO4) against intravenous administration of CP in male and female rats. METHOD: In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO4 and were compared with the control groups. RESULTS: CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO4 supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO4 supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO4-treated group (BUN: P=0.002, Cr: P=0.005, KTDS: P=0.002, and KW: P=0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone (P male = 0.002 and P female = 0.001), and the mid- and high doses of MgSO4 supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (P=0.05) and high (P=0.032) doses of MgSO4-treated groups. CP accompanied with the mid-dose of MgSO4 supplement reduced the KTDS (P male = 0.04 and P female = 0.004) and KW (P male = 0.002 and P female = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: P=0.002 and KW: P=0.031). CP accompanied with three different doses of MgSO4 supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group. CONCLUSION: The renal protective effect of MgSO4 could be dose and gender related.

Age and Gender Related Renal Side Effects of Cisplatin in Animal Model

Backgrounds: Cisplatin (CDDP) is a choice of anti-cancer drug for cancer chemotherapy with serious side effects such as nephrotoxicity. It seems that age is an important factor influencing the side effects of CDDP. This study was designed to determine the role of age and gender simultaneously in CDDP induced renal toxicity. Methods: 40 Wistar male and female rats were assigned as 6 groups in 3 different age categories (10, 16, and 20 weeks old). The single dose of CDDP (7.5 mg/kg, ip) was administrated, and a week later measurements were performed. Results: Body weight changes in male (not in female) animals aged 16 and 20 weeks were more than 10 weeks old animals (P<0.05). In male rats, the serum levels of creatinine (Cr) and blood urea nitrogen (BUN), and Cr-clearance in aged 10 weeks, normalized kidney weight (KW) in aged 20 weeks, and serum nitrite, aspartate aminotransferase (AST) and malondialdehyde (MDA) levels and kidney tissue damage score (KTDS) in rats aged 16 weeks were significantly altered (P<0.05). Gender difference in serum level of Cr, BUN and nitrite, and Cr-clearance were observed in animals aged10 weeks (P<0.05). Conclusion: The side effects of CDDP are gender depended, and may be different at various ages.

Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences

Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.

Co-Administration of Silymarin and Deferoxamine against Kidney, Liver and Heart Iron Deposition in Male Iron Overload Rat Model.

BACKGROUND: Tissue iron deposition may disturb functions of the organs. In many diseases like thalassemia, the patients suffer from iron deposition in kidney and heart tissues. Deferoxamine (DF) is a synthetic iron chelator and silymarin (SM) is an antioxidant and also a candidate for iron chelating. This study was designed to investigate the effect of DF and SM combination against kidney and heart iron deposition in an iron overload rat model. METHODS: Male Wistar rats were randomly assigned to 5 groups. The iron overloading was performed by iron dextran 100 mg/kg/day every other day during 2 weeks and in the 3(rd) week, iron dextran was discontinued and the animals were treated daily with combination of SM (200 mg/kg/day, i.p.) and DF (50 mg/kg/day, i.p.) (group 1), SM (group 2), DF (group 3) and saline (group 4). Group 5 received saline during the experiment. Finally, blood samples were obtained and kidney, heart and liver were immediately removed and prepared for histopathological procedures. RESULTS: The results indicated no significant difference in kidney function and endothelial function biomarkers between the groups. However, combination of SM and DF did not attenuate the iron deposition in the kidney, liver and heart. DF alone, rather than DF and SM combination, significantly reduced the serum level of malondialdehyde (P < 0.05). Co-administration of SM and DF significantly increased the serum level of ferritin (P < 0.05). CONCLUSIONS: DF and SM may be potentially considered as iron chelators. However, combination of these two agents did not provide a protective effect against kidney, liver and heart iron deposition.

Effect of testosterone on Cisplatin-induced nephrotoxicity in surgically castrated rats.

BACKGROUND: Cisplatin (CP) is an important antitumor drug with serious side effects such as nephrotoxicity. Estrogens can affect CP-induced nephrotoxicity; however, the role of testosterone (TS), the main male sex hormone, is not clear. OBJECTIVES: This study aimed to investigate the effect of TS on CP-induced nephrotoxicity in castrated male rats. MATERIALS AND METHODS: A total of 54 male Wistar rats were castrated and allocated into eight groups. Groups 1 through 3 respectively received 10, 50, and 100 mg/kg/wk of TS and group 4 received sesame oil for four weeks; then all four groups received 2.5 mg/kg/d CP for one week. Groups 5 through 8 received the same treatment regimen as groups 1 through 4 during first four weeks but instead of CP, they received saline for one week. Then the animals were sacrificed for biochemical and histopathologic studies. RESULTS: CP increased the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and malondialdehyde (SMDA) as well as kidney weight (KW), bodyweight (BW) loss, and kidney tissue damage score (KTDS). It significantly decreased the serum and kidney levels of nitrite and serum level of TS in comparison with the control group (P < 0.05). However, coadministration of CP and low dose of TS significantly decreased the serum levels of BUN as well as Cr and KTDS (P < 0.05). Administration of high-dose TS alone increased the SMDA level, KTDS, and KW while decreased the BW significantly (P < 0.05). CONCLUSIONS: It seems that testosterone in low dose, i.e. physiologic dose, protects kidneys against CP-induced nephrotoxicity; however, special care is needed in CP therapy of patients with high levels of TS.

A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats.

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II; CP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. Cisplatin induced nephrotoxicity consists of change in kidney weight, histological changes in kidney and increase in serum creatinine (Cr) and blood urea nitrogen (BUN). This study was designed to find out a model for prediction of cisplatin induced nephrotoxicity. MATERIALS AND METHODS: Pathological damage score, kidney weight, BUN, and Cr of 227 rats that were involved in different projects were determined. A total of 187 rats were treated with 7 mg/kg cisplatin and sacrificed 1 week later. RESULTS: There was a good significant correlation between normalized kidney weight and logarithmic scale of BUN and Cr. Relationship between BUN, Cr or normalized kidney weight and pathology damage score was significant. CONCLUSION: Normalized kidney weight and pathology damage score is a good predictor of renal function in cisplatin induced nephrotoxicity in experimental rats.

Effects of Fennel Essential Oil on Cisplatin-induced Nephrotoxicity in Ovariectomized Rats.

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II (CDDP)) is an effective drug in cancer therapy to treat solid tumors. However, the drug is accompanied by nephrotoxicity. Previous reports indicated that estrogen has no protective role against CDDP-induced nephrotoxicity, but the role of phytoestrogen as an estrogenic agent in plants is not determined yet. The major composition of fennel essential oil (FEO) is trans-anethole that has estrogenic activity; so, we used FEO as a phytoestrogen source against CDDP-induced nephrotoxicity. MATERIALS AND METHODS: Fifty-four ovariectomized Wistar rats were divided into seven groups. Groups 1-3 received different doses of FEO (250, 500, and 1000 mg/kg/day, respectively) for 10 days. Group 4 received saline for 10 days plus single dose of CDDP (7 mg/kg, intraperitoneally (ip)) at day 3. Groups 5-7 received FEO similar to groups 1-3, respectively; plus a single dose of CDDP (7 mg/kg, ip) on day 3. On day 10, the animals were sacrificed for histopathological studies. RESULTS: The serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW) and body weight changes in CDDP-treated groups increased significantly (P < 0.05). FEO did not reduce the levels of BUN and Cr, KTDS, and KW and body weight changes. Also, the serum and tissue levels of nitrite were not altered significantly by FEO. CONCLUSION: FEO, as a source of phytoestrogen, did not induce kidney damage. In addition, FEO similar to estrogen was not a nephroprotectant agent against CDDP-induced nephrotoxicity.

Sex differences in protective effect of recombinant human erythropoietin against cisplatin-induced nephrotoxicity in rats.

INTRODUCTION: The protective role of recombinant human erythropoietin (RHE) against cisplatin-induced nephrotoxicity has been reported, but the role of sex differences is not clearly known. The aim of this study was to determine the sex-based difference in the protective effect of RHE against cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: Thirty-three Wistar rats were divided into 6 groups. According to protocol l, male and female rats were treated with RHE (100 IU/kg/d) for 3 days and then received a single dose of cisplatin (7 mg/kg). According to protocol 2, the rats received the same single dose of cisplatin and then were treated with RHE for 7 days. Two other groups of male and female rats received a similar regimen of protocol 2 except for saline instead of RHE. All the animals were sacrificed 1 week after cisplatin administration. RESULTS: All of the experimental animals experienced weight loss. The percentage change of weight in male rats with protocol 1 was significantly less than that in male rats in protocol 2 and control groups. However, in female groups, the percentage of change in weights was slightly higher with protocol 2 than with protocol 1 and control treatment. Administration of RHE significantly decreased changes in serum creatinine, BUN, and malondialdehyde levels in male rats, but not in females. No significant difference was observed in serum nitrite level, kidney weight, and kidney damage score between the groups. CONCLUSIONS: This study suggested that erythropoietin may lead to different responses against cisplatin-induced nephrotoxicity in male and female rats.

Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia-reperfusion in rat model.

BACKGROUND: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats. METHODS: Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process. RESULTS: The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group (P < 0.05). EPO administration decreased levels of BUN and Cr significantly (P < 0.05), and KTDS and KW insignificantly (P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite (P < 0.05). CONCLUSIONS: EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.

Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.

BACKGROUND: Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. MATERIALS AND METHODS: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. RESULTS: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01). CONCLUSION: Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

Protective Role of Silymarin and Deferoxamine Against Iron Dextran-induced Renal Iron Deposition in Male Rats.

BACKGROUND: Kidney iron deposition (KID) is caused by iron overload that is observed in kidney diseases and anemia. The protective effects of deferoxamine (DF) and silymarin (SM) were studied against iron overload-induced KID in rat model. METHODS: Rats received iron dextran (200 mg/kg) for a period of 4 weeks every other day, but at the beginning of week 3, they also were subjected to a 2-week (every other day) treatment with vehicle (group 2, positive control), SM (200 mg/kg; group 3), DF (50 mg/kg; group 4), SM (400 mg/kg; group 5), and combination of SM and DF (200 and 50 mg/kg, respectively; group 6). Group 1, as the negative control, received saline alone during the study. The levels of serum creatinine (Cr), blood urea nitrogen (BUN), iron, ferritin, and nitrite were determined, and the kidney was removed for histopathological investigations. RESULTS: Before treatment, the serum levels of iron and ferritin in all iron dextran receiver groups were significantly higher than those of the negative control group (P < 0.05). However, the serum levels of BUN, Cr, and nitrite were not different between the groups. No statistical differences were detected in kidney weight and the serum levels of BUN, Cr, iron, ferritin, and nitrite after 2 weeks of treatment with SM, DF, or combination of both. The SM and DF treatments reduced the intensity of the KID, but only in the SM (200 mg/kg) group, a significant reduction in KID was observed (P < 0.05). CONCLUSION: It seems that SM is a nephroprotectant agent against KID in acute iron overload animal models.

Estrogen Abolishes Protective Effect of Erythropoietin against Cisplatin-Induced Nephrotoxicity in Ovariectomized Rats.

Introduction. Nephrotoxicity is one the side effect of cisplatin therapy and erythropoietin has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompained with estrogen has not been studied in female. Methods. 27 ovariectomized female Wistar rats divided into five groups. Groups 1 & 2 received estradiol valerate (0.5 mg/kg/week) for four weeks, and single dose of cisplatin (7 mg/kg, ip) was administrated at the end of week 3. Then the group 1 was treated with erythropoietin (100 U/kg/day), and the group 2 received vehicle during week 4. Groups 3 and 4 were treated similar to group 1 and 2, except for placebo instead estradiol valerate. Group5 (negative control) received placebo during the study. Animals were killed at the end of week 4. Results. In non-erythropoietin treated rats, cisplatin significantly increased the serum levels of blood urea nitrogen and creatinine (P < 0.05). However, these biomarkers significantly decreased by erythropoietin (P < 0.05). The weight loss, kidney weight, and kidney tissue damage score in rats treated with cisplatin but without estradiol were significantly less than the values in similar group when estradiol was present (P < 0.05). Conclusion. It seems that erythropoietin could protect the kidney against cisplatin-induced nephrotoxicity. This protective effect was not observed when estrogen was present.

Epidemiology of four main nosocomial infections in Iran during March 2007 - March 2008 based on the findings of a routine surveillance system.

BACKGROUND: Annually, around six million patients are admitted to hospitals in Iran. Information about the prevalence of nosocomial infections (NIs) is necessary for both appropriate management and establishment of preventative measures in hospitals. This article is based on the findings of the Nosocomial Infection Surveillance System (NISS) which has been providing information on NIs in Iran since March 2007.  METHODS: NISS covers 95 hospitals throughout Iran, each with over 200 beds. There are four main infections: urinary tract infection (UTI), surgical site infection (SSI), bloodstream infection (BSI) and pneumonia (PNEU) included in NISS. Reports are completed on forms that have been provided based on national guidelines. In all selected hospitals there is one designated nurse who conducts infection control activities and is trained in the detection and reporting of NIs based on NISS guidelines. RESULTS: During March 2007 - March 2008, a total of 1,879,356 patients were admitted to the selected hospitals. The total detected NIs were 10557 with a prevalence of 0.57%. Of these, UTI was the most prevalent infection (32.2%) and BSI was the least (16.3%). Based on gender, females had more UTI, whereas PNEU was the highest in males. Of reported NIs, 9% were detected in children less than five years of age and included BSI (45%), PNEU (20%), SSI (19%) and UTI (16%). There were 26% reported NIs in the age group over 65 years, of which the most prevalent infections were UTI (42%) followed by PNEU (31%), SSI (15%) and BSI (12%). NIs were most often detected in intensive care units (ICUs; 26.7%), followed by surgery wards (12.8%). CONCLUSION: In comparison with other studies and the World Health Organization (WHO) estimates, the rate of NIs appears to be less according to NISS. NISS has the capability to provide basic information for efficient management and control measures, in addition to indicating variations in NIs based on gender, age and location (hospital ward). In order to have a more realistic estimate of NIs and strengthen NISS, it is advisable to conduct a point prevalence study.

The Role of Magnesium Supplementation in Cisplatin-induced Nephrotoxicity in a Rat Model: No Nephroprotectant Effect.

OBJECTIVES: Cisplatin (CP) is used as the commonest drug to treat solid tumors. It is accompanied by a nephrotoxicity side effect. The main objective of this study is to investigate the protective role of magnesium (Mg) supplementation in CP-induced nephrotoxicity in a rat model. METHODS: Twenty-nine Wistar rats were randomly assigned to four groups (1-4). Groups 1-3 received 20, 80, and 200 mg/kg magnesium sulfate respectively, for 10 days, but on day 3, a single dose of CP (7 mg/kg, i.p.) was also injected. Group 4 (positive control group) received the same regimen of Groups 1-3 except saline instead magnesium sulfate. One week after CP administration, blood samples were obtained and all animals were killed for kidney histopathological investigations. RESULTS: All CP-treated animals lost weight, and the percentage of weight loss in Group 1 (low dose Mg sulfate treated) was significantly higher compared with the positive control group (Group 4, P < 0.05). The increase in blood urea nitrogen (BUN) and creatinine (Cr) levels in serum in Group 1 were more than those in other groups (P < 0.05). No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group (P < 0.05). CONCLUSION: Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain.

A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in rats.

INTRODUCTION: The nephroprotective effect of co-administration of vitamin C and losartan as prophylaxis against cisplatin-induced nephrotoxicity (CIN) was evaluated. MATERIALS AND METHODS: Co-administration of vitamin C and losartan was compared with losartan (10 mg/kg), vitamin C (250 mg/kg), and placebo in 4 groups of rats with CIN. The prophylactic agents were injected daily for a period of 4 days, and on day 3, a single dose (6 mg/kg) of cisplatin was administrated. The animals were sacrificed 7 days later for pathological examination of the kidneys. RESULTS: Cisplatin prevented the animals' weight gain. The serum levels of creatinine and blood urea nitrogen increased within the groups with CIN, but no significant difference was observed between the groups. The prophylaxis has no effect on serum osmolality, total protein, or nitrite concentrations. The kidney tissue damage was scored, and losartan provided a lower damage score than vitamin C and a combination of vitamin C and losartan. CONCLUSIONS: We concluded that co-administration of vitamin C and losartan was not more effective than the administration of vitamin C or losartan alone.

A histopathological study of nephrotoxicity, hepatoxicity or testicular toxicity: Which one is the first observation as side effect of Cisplatin-induced toxicity in animal model?

BACKGROUND: Cisplatin (CP) is widely used in clinic to treat the solid tumors. However, CP is associated with some major side effects including nephrotoxicity, hepatoxicity, and testicular toxicity. OBJECTIVES: To found, which of the toxicities is the first side effect of CP. MATERIALS AND METHODS: we conducted a pilot research on 12 adult male Wistar rats. RESULTS: One week after CP administration, the induced toxicity was observed clearly in kidney tissue. The only abnormality that observed in testis tissue was very small degree of hyaline casts. However, no damage and other abnormality were detected in the liver tissue. CONCLUSIONS: According to these findings, in clinic, first special attention must be made on kidneys during chemotherapy with CP. However, the duration of experiment is suggested to be extended to obtain hepatoxicity or testicular toxicity model in experimental animal in laboratories. Moreover, different dose of CP should be used to study the first side effect in animal model.

The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model.

BACKGROUND: Cisplatin (CP) as a potential drug for solid tumors produces nephrotoxicity and disturbs endothelial function. CP induced nephrotoxicity may be gender related. Nitric oxide plays a pivotal role in endothelial function and L-arginine as endogenous NO donor promotes endothelial function. The role of L-arginine in CP induced nephrotoxicity model and its gender related was investigated in this study. METHODS: Thirty three Wistar rats were randomly assigned to four groups. The groups 1 (male, n = 6) and 2 (female, n = 11) received a single dose of L-arginine (300 mg/kg, ip), and the day after, they received a single dose of CP (7 mg/kg). The group 3 (male, n = 9) and 4 (female, n = 7) were assigned to the same regimen except for saline instead of L-arginine. All animals were sacrificed one week after CP administration. The levels of blood urea nitrogen (BUN), creatinine and nitrite were measured. The kidneys were also removed for pathological investigations. RESULTS: Five animals died. All CP treated animals lost weight. The normalized weigh loss was significantly different between male and female in CP+L-arginine treated animals (p < 0.05). BUN and creatinine were increased significantly in male treated with CP and in female treated with CP+L-arginine (p < 0.05). L-arginine reduced BUN in male (not in female) when compared with control groups (p < 0.05). The level of nitrite was increased significantly in L-arginine treated animals. Kidney tissue damage score and normalized kidney weight were greater in females treated with CP+ L-arginine than female received CP alone (p < 0.05). CONCLUSIONS: L-arginine may protect against CP induced nephrotoxicity in male, but it promotes the induced damage in female. The exact mechanism need to be defined.