The Role of Gamma Amino Butyric Acid in Cisplatin-induced Nephrotoxicity in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Diabetes mellitus can change the risk of developing cancer. Cisplatin (CP) is a common antineoplastic drug. The major side effect of CP is nephrotoxicity. Gamma amino butyric acid (GABA) is an antioxidant agent that may have a protective role against CP-induced nephrotoxicity. The aim of the present study was to investigate the role of GABA in CP-induced nephrotoxicity in hyperglycemic male and female rats.

MATERIALS AND METHODS: Sixty male and female Wistar diabetic rats were used in ten experimental groups. GABA alone groups received GABA (50 μmol/kg/d i.p.) for 12 days. CP alone groups received CP (2.5 mg/kg/d i.p.) for 6 days. Other groups received GABA in the form of therapy (T) + CP, prophylaxis (P) + CP, and prophylaxis-treatment (PT) + CP. Finally, blood samples were obtained, and animals were killed for kidney tissue investigation.

RESULTS: In female rats, the serum levels of creatinine (Cr) did not change by GABA rather than CP and also there were no significant changes in blood urea nitrogen to creatinine ratio (BUN/Cr). In male rats, plasma Cr level increased by GABA (P) and (T). Body weight loss was significantly different among groups (P < 0.05). BUN/Cr ratio significantly increased in CP and GABA (PT) + CP groups. In two genders, plasma Cr level significantly decreased in CP groups (P < 0.05). The kidney levels of malondialdehyde enhanced significantly in CP groups.

CONCLUSION: Hyperglycemia has protective effect against CP-induced nephrotoxicity. GABA did not change this effect in female, but in male in the form of PT, GABA maintained it.