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.

Sex Differences in the Renal Vascular Responses of AT1 and Mas Receptors in Two-Kidney-One-Clip Hypertension.

BACKGROUND: The prevalence and severity of hypertension, as well as the activity of the systemic and local renin angiotensin systems (RASs), are gender related, with more symptoms in males than in females. However, the underlying mechanisms are not well understood. In this study, we investigated sex differences in renal vascular responses to angiotensin II (Ang II) administration with and without Ang II type 1 and Mas receptor (AT1R and MasR) antagonists (losartan and A779) in the 2K1C rat model of renovascular hypertension. METHODS: Male and female 2K1C rats were divided into 8 experimental groups (4 of each sex) treated with vehicle, losartan, A779, or A779+losartan. Responses of mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) to Ang II were determined. RESULTS: In both sexes, the basal MAP, RBF, and RVR were not significantly different between the four groups during the control period. The Ang II administration decreased RBF and increased RVR in a dose-related manner in both sexes pretreated with vehicle or A779 (P dose < 0.0001), but in vehicle pretreated groups, RBF and RVR responses were different between male and female rats (P group < 0.05). AT1R blockade increased RBF and decreased RVR responses to Ang II, and no difference between the sexes was detected. Coblockades of AT1R and MasR receptors increased RBF response to Ang II significantly in males alone but not in females (P group=0.04). CONCLUSION: The impact of Ang II on RBF and RVR responses seems to be gender related with a greater effect on males, and this sex difference abolishes by Mas receptor blockade. However, the paradoxical role of dual losartan and A779 may provide the different receptor interaction in RAS between male and female rats.

Health care-associated infections, including device-associated infections, and antimicrobial resistance in Iran: The national update for 2018.

Introduction: Surveillance of health care-associated infections (HAIs) is an essential part of an efficient healthcare system. This study is an update on incidence and mortality rates of HAIs in Iran in 2018. Methods: Almost all hospitals across the country (940 hospitals) entered the data of HAIs and denominators to the Iranian Nosocomial Infections Surveillance (INIS) software. Statistics were derived from INIS. Results: From 9,607,213 hospitalized patients, 127,953 suffered from HAI, 15.65% of whom died. The incidence rate of HAI was calculated as 4.2 per 1000 patient-days. Considering relative frequencies among HAIs, Pneumonia (29.1%) and UTIs (25.6%) were the most common types of infection. Ventilator-associated pneumonia (VAP) was the most frequent device-associated infection (DAI) 25.66 per 1000 ventilator-days, and had the highest mortality rate (43.08%). Incidence density of other DAIs was 5.43 for catheter-associated UTI and 2.86 for catheter-associated BSI per 1000 device-days. Medical ICUs had the highest incidence and percentage of deaths (15.35% and 37.63%, respectively). The most causative organisms were Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumonia. The rate of methicillin-resistance Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria was about 49%, 57%, and 58% respectively. Conclusion: This study provided an overview of HAIs in Iran and indicated that HAIs required special attention both in detection/reporting and in infection control measures. Future studies could be done on adherence rate of DAIs' preventive bundles, interventions via multimodal strategies, evaluating the effect of training, and effect of antibiotic stewardship programs.

Health care-associated infections in Iran: A national update for the year 2015.

BACKGROUND: A national surveillance system for health care-associated infections (HAIs) in Iran is relatively new, and an update on incidence and mortality rates can aid clinicians and stakeholders in development of new guidelines and imperative modifications to be made. METHODS: Data were extracted from the national HAIs surveillance software for more than 7 million hospitalizations during 2015. Data regarding age, gender, deaths, ward of admission, and microbiologic findings were collected and analyzed. RESULTS: From 491 hospitals, 7,018,393 hospitalizations were reported during 2015; 82,950 patients had been diagnosed with at least 1 HAI, 6,355 of whom died (crude fatality rate, 7.7). Men comprised 51.4% of the patients. The incidence rate was calculated to be 1.18. Urinary tract infections and pneumonia were the most commonly reported infections (27.9% and 23.8%) and 33% of patients were older than age 65 years. Intensive care units had the highest incidence rates, followed by burn units with incidence rates close to 9. Highest percentages of deaths were reported among patients with an HAI in the intensive care unit (20.6%) and those with pneumonia (39.6%). CONCLUSION: Although the underreporting of HAIs hinders accurate calculation of incidence, the present study provides a general update. The results can help in modification of national guidelines and appropriate choice of antimicrobial agents in the management of HAIs.

Time course of cisplatin-induced nephrotoxicity and hepatotoxicity.

BACKGROUND: One of the main therapeutic limitations of cisplatin (CP) is nephrotoxicity which is time-dependent. OBJECTIVES: The purpose of this study was to determine the optimal timing for initiation of CP toxicity. MATERIALS AND METHODS: Sixty male and female Wistar rats were randomly divided into five groups. All the animals in groups 2-5 received single dose of CP (10 mg/kg; i.p.), and were evaluated 25, 50, 75, and 100 hours after CP administration. Group 1 as an untreated group did not receive any agent and was considered as time zero. RESULTS: The data indicated time-dependent progression of kidney and hepatic toxicity due to CP administration. Histological examination showed increase in kidney tissue damage score (KTDS) at hour 25, which peaked 75-100 hours after CP administration. Significant body weight loss and reduction of alkaline phosphatase (ALP) 50 hours after CP injection were observed. Blood urea nitrogen (BUN), creatinine (Cr), and serum nitrite increased significantly 75 hours after CP injection. Also, enhancement of kidney and testis weights, and alkaline aspartate aminotransferase (AST) level; and reduction of alanine aminotransferase (ALT) level and uterus weight occurred significantly 100 hours after the injection, while kidney malondialdehyde level enhanced significantly 75 hours after CP administration. CONCLUSIONS: These findings suggest that the CP-induced nephrotoxicity started to develop almost 3 days after administration of the drug in rats. CP surprisingly reduced the serum levels ALP and ALT while AST increased 100 hours after CP injection. CP-induced nephrotoxicity and hepatotoxicity are time-dependent, and the related biomarkers may alter by different trends.

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.

Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats.

BACKGROUND: Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is considered as its major side effect. Aerobic exercise is well known as an approach to reduce the side effects of many drugs. OBJECTIVES: This study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity. MATERIALS AND METHODS: Thirty male Wistar rats were randomly divided into four groups. Group I had aerobic exercise on a treadmill one hour per day and five days per week for eight weeks. Then, the exercise protocol was continued for another week, but during this week, the animals also received CP (2.5 mg/kg/day; ip). Group II underwent the same protocol as group I without exercise in the last week during the CP therapy. Groups III and IV were assigned as positive and negative control groups, and were treated with CP and saline without exercise, respectively. Finally, the animals were sacrificed for the biochemical measurement and tissue histopathology investigation. RESULTS: CP alone without exercise increased serum levels of blood urea nitrogen (BUN), creatinine (Cr), and malondialdehyde (MDA); and kidney nitrite level, while treadmill exercise in group I significantly ameliorated these parameters (P < 0.05). Kidney and serum levels of MDA and nitrite did not alter significantly. Also, the severity of kidney tissue damage decreased significantly in groups I and II (P < 0.05). CONCLUSIONS: Aerobic exercise may reduce CP-induced nephrotoxicity with a favorable effect on renal function by increasing activation of antioxidant system.

Nonpreventive Role of Aerobic Exercise Against Cisplatin-induced Nephrotoxicity in Female Rats.

BACKGROUND: Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is a major concern for CP therapy. CP-induced nephrotoxicity is gender-dependent, and the effect of aerobic exercise in females has not been reported yet while it has a beneficial effect in males. Hence, this study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity in female rats. METHODS: Twenty-eight adult female rats were divided into four groups. Groups I and II had aerobic exercise on a treadmill for 8 weeks. Then, the exercise protocol was continued for another week in group I and stopped in group II. All animals in these groups received CP (2.5 mg/kg/day; i.p.) for 1-week. Groups III and IV were treated with CP and vehicle, respectively, without exercise. Finally, the animals were sacrificed for biochemical measurements and tissue histopathology investigations. RESULTS: CP alone without exercise increased serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney weight, and kidney tissue damage score (KTDS); while exercise could not attenuate these parameters in female rats. Exercise in females increased the serum levels of BUN and Cr and KTDS and weight loss (P < 0.05). Kidney nitrite levels reduce significantly in group I in compared to positive and negative control groups. Exercise also did not have beneficial effects on malondialdehyde levels in plasma and kidney. CONCLUSIONS: Aerobic exercise cannot reduce CP-induced nephrotoxicity in female rats. Increasing the damage in female rats may be related to female sex hormone estrogen or gender differences in renal hemodynamic and renin-angiotensin system activity in the presence of exercise. In general, it is recommended that the females under CP chemotherapy avoid exercising during treatment.

Effect of L-arginine and L-NAME on Kidney Tissue Damage in Rats after 24 h of Bilateral Ureteral Obstruction.

BACKGROUND: Bilateral ureteral obstruction (BUO) affects renal function adversely. Previous investigations have implied that nitric oxide (NO) improves renal function in obstructive nephropathy. The aim of the current study was to investigate the role of NO precursor, L-arginine, and NO blocker agent, L-NAME on kidney tissue damage in rats after 24 h of BUO. METHODS: Forty Wistar rats (18 male, 22 female) were divided into four groups as follows; group 1: Sham or negative control group that received saline 3 days prior to the sham operation, group 2: Vehicle or positive control group that received saline 3 days prior to BUO, and groups 3 and 4: L-arginine and L-NAME groups that were treated same as group 2 except L-arginine (300 mg/kg) and L-NAME (4 mg/kg) instead of saline, respectively. Twenty-four hours after obstruction, the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, and malondialdehyde (MDA) as well as kidney tissue levels of nitrite and MDA were measured and histopathological studies were done on left kidney. RESULTS: The serum levels of BUN and Cr and kidney and body weights increased and the tissue levels of MDA and nitrite decreased significantly in all BUO groups (P < 0.05). However, the tissue damage score was significantly lower in the L-arginine treated group in comparison to the vehicle and L-NAME groups (P < 0.05). As expected, the serum level of nitrite significantly increased in the L-arginine group (P < 0.05). CONCLUSIONS: Endogenous NO donor; L-arginine, may protect the kidney tissue against BUO. However, this renoprotective role of L-arginine did not attenuate the increased kidney function markers (BUN and Cr) induced by obstruction.

Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Chemotherapy with cisplatin (CP) is accompanied with nephrotoxicity. OBJECTIVES: In the current study, pomegranate flower extract (PFE) has been evaluated as an antioxidant agent against CP-induced-renal toxicity. MATERIALS AND METHODS: Thirty two male Wistar rats were divided into five groups (6-8 in each group). The animals in groups 1 to 3 received PFE (25 mg/kg), PFE (50 mg/kg), and placebo (saline), respectively for 9 days, and onset of the day 3, they also received CP (2.5 mg/kg/day). Groups 4 and 5 were treated with PFE (25 and 50 mg/kg/day) for 9 days. Finally, the animals were sacrificed at day 9 after collecting blood samples. Kidneys were removed, weighted, and underwent histopathological investigation. RESULTS: The mean serum level of creatinine in group 3 (treated with CP and placebo) increased significantly (p<0.05), but the value decreased significantly (p<0.05) in group 1. Kidney weight in group 1 was lower than KW in groups 2 and 3, however it was significant when compared with group 2 (p<0.05). The serum nitrite level in group 2 was non-significantly lower than that in other groups, and no significant changes were observed in serum levels of malondialdehyde (MDA). Tissue level of nitrite was significantly decreased in the positive control and high dose of PFE plus CP-treated groups (p<0.05). Among CP-treated groups, low dose of PFE significantly improved kidney nitrite level (p<0.05). The results from histopathological staining indicated less tissue damage in group 1 when compared with group 3. CONCLUSIONS: It seems that low dose of PFE plays a protective role against CP-induced renal toxicity in rats.

Vascular Response to Graded Angiotensin II Infusion in Offspring Subjected to High-Salt Drinking Water during Pregnancy: The Effect of Blood Pressure, Heart Rate, Urine Output, Endothelial Permeability, and Gender.

Introduction. Rennin-angiotensin system and salt diet play important roles in blood pressure control. We hypothesized that the high-salt intake during pregnancy influences the degree of angiotensin-dependent control of the blood pressure in adult offspring. Methods. Female Wistar rats in two groups (A and B) were subjected to drink tap and salt water, respectively, during pregnancy. The offspring were divided into four groups as male and female offspring from group A (groups 1 and 2) and from group B (groups 3 and 4). In anesthetized matured offspring mean arterial pressure (MAP), heart rate and urine output were measured in response to angiotensin II (AngII) (0-1000 ng/kg/min, iv) infusion. Results. An increase in MAP was detected in mothers with salt drinking water (P < 0.05). The body weight increased and kidney weight decreased significantly in male offspring from group 3 in comparison to group 1 (P < 0.05). MAP and urine volume in response to AngII infusion increased in group 3 (P < 0.05). These findings were not observed in female rats. Conclusion. Salt overloading during pregnancy had long-term effects on kidney weight and increased sex-dependent response to AngII infusion in offspring (adult) that may reveal the important role of diet during pregnancy in AngII receptors.

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.

Pomegranate Flower Extract does not Prevent Cisplatin-Induced Nephrotoxicity in Female Rats.

BACKGROUND: Nephrotoxicity is the major side-effect of cisplatin (CDDP), and it is reported to be gender-related. We evaluated the effects of pomegranate flower extract (PFE) as an antioxidant on CDDP-induced nephrotoxicity in female rats. METHODS: Twenty-three adult female rats in four groups treated as following. Groups 1 and 2 received PFE at doses of 25 and 50 (mg/kg/day), respectively, for 9 days, and from day 3 on, they also received cisplatin (CDDP) (2.5 mg/kg) daily. Group 3 was treated as group 1 expects saline instead of PFE, and group 4 received PFE (25 mg/kg/day) alone. RESULTS: Cisplatin alone increased the serum levels of blood urea nitrogen, creatinine, and nitrite; and kidney tissue damage score and kidney weight. However, PFE not only did not ameliorate the induced nephrotoxicity, but also aggravated renal tissue damage. CONCLUSIONS: Pomegranate extract as an antioxidant did not ameliorate CDDP-induced nephrotoxicity in female rats.

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.

N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal Ischemia/Reperfusion Injury in Rat.

BACKGROUND: One of the most common causes of acute kidney injury (AKI) is kidney ischemia/reperfusion injury (IRI). The distant organ injury such as acute lung injury is one of the side effects of AKI or kidney IRI. In this study, we performed bilateral renal IRI in rats and the protective role of N-acetylcysteine (NAC) in kidney and lung was investigated. METHODS: Rats (n = 30) were randomly assigned to four experiment groups. The group 1 was assigned as sham-operated group. Before kidney IRI performance, the others groups were treated with saline (group 2), 150 mg/kg (group 3) or 500 mg/kg (group 4) of NAC, and the treatment were continued daily after IRI for next 3 days. At day 3, the all groups' animals were subjected for the measurements. RESULTS: The serum level of blood urea nitrogen (BUN) and creatinine (Cr) in the control group increased significantly (P < 0.05), and administration of NAC (150 mg/kg) decreased the serum levels of Cr and BUN. However, only the serum level of Cr decreased significantly (P < 0.05). NAC did not improve kidney weight and damage; however, its low dose (150 mg/kg) attenuated the lung injury score (P < 0.05) when compared with the control group. No significant differences were observed in lung water content and endothelial permeability, serum levels of malondialdehyde and nitrite between the groups. CONCLUSIONS: Low dose of NAC as a protectant agent may protect the kidney function and lung tissue damage after kidney IRI.

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.

Inhibition of Nitric Oxide Synthase by L-NAME Promotes Cisplatin-Induced Nephrotoxicity in Male Rats.

Objective. Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats. Methods. Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male, n = 6 and group 2, female, n = 6) received saline. Groups 3 (male, n = 8) and 4 (female, n = 8) were treated with L-NAME (4 mg/kg, i.p.), and groups 5 (male, n = 8) and 6 (female, n = 8) received CP (3 mg/kg) for 7 days. Groups 7 (male, n = 8) and 8 (female, n = 8) were treated with L-NAME and CP for 7 days. Results. The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats (P < 0.05). CP alone increased kidney damage significantly (P < 0.05 ), however, the damage induced by combination of CP and L-NAME was gender-related. Conclusion. NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related.