Nasiri Masoomeh, Soltani Nepton, Mazaheri Safoora, Maleki Maryam, Talebi Ardeshir, Gharibi Fatemah, Nematbakhsh Mehdi
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Physiology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Adv Biomed Res. 2017 Jul 31;6:96. doi: 10.4103/2277-9175.211834. eCollection 2017.
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.
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.
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 ( < 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 ( < 0.05). The kidney levels of malondialdehyde enhanced significantly in CP groups.
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.
糖尿病可改变患癌风险。顺铂（CP）是一种常用的抗肿瘤药物。CP的主要副作用是肾毒性。γ-氨基丁酸（GABA）是一种抗氧化剂，可能对CP诱导的肾毒性具有保护作用。本研究的目的是探讨GABA在高血糖雄性和雌性大鼠CP诱导的肾毒性中的作用。
60只雄性和雌性Wistar糖尿病大鼠被用于10个实验组。单独使用GABA的组腹腔注射GABA（50 μmol/kg/d），持续12天。单独使用CP的组腹腔注射CP（2.5 mg/kg/d），持续6天。其他组接受治疗（T）+CP、预防（P）+CP和预防-治疗（PT）+CP形式的GABA。最后，采集血样，并处死动物以进行肾脏组织研究。
在雌性大鼠中，GABA对血清肌酐（Cr）水平没有影响，而CP有影响，血尿素氮与肌酐比值（BUN/Cr）也没有显著变化。在雄性大鼠中，GABA（P）组和（T）组的血浆Cr水平升高。各组间体重减轻有显著差异（P<0.05）。CP组和GABA（PT）+CP组的BUN/Cr比值显著升高。在两种性别中，CP组的血浆Cr水平显著降低（P<0.05）。CP组肾脏丙二醛水平显著升高。
高血糖对CP诱导的肾毒性有保护作用。GABA在雌性中未改变这种作用，但在雄性中以PT形式使用时，GABA维持了这种作用。
