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.

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.

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.

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.

Background: Renal ischemia/reperfusion (I/R) injury may be related to activity of reninangiotensin system (RAS), which is gender-related. In this study, it was attempted to compare the effect of angiotensin II (Ang II) receptor type 1 (AT1R) blockade; losartan in I/R injury in male and female rats. Materials and Methods: Male and female Wistar rats were assigned as sham surgery, control I/R groups treated with vehicle, and case I/R groups treated with losartan (30 mg/kg). Vehicle and losartan were given 2 hours before bilateral kidney ischemia induced by clamping renal arteries for 45 minutes followed by 24 hours of renal reperfusion. Results: The I/R injury significantly increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr), and kidney tissue damage score in both genders. However, losartan decreased these values in female rats significantly (P < 0.05). This was not observed in male rats. Conclusion: Losartan protects the kidney from I/R injury in female but not in male rats possibly because of gender-related difference of RAS.