Evaluation of the Protective Effects of Alpha Lipoic Acid on Bleomycin-Induced Ovarian Toxicity

Abstract

Chemotherapeutic drugs administered during cancer therapy, may lead to the depletion of ovarian follicles, and subsequent infertility in fertile patients. We aimed to determine toxic effects of bleomycin (BLM) on rat ovary, and to evaluate protective effects of alpha lipoic acid (ALA) on BLM toxicity. The total of 30 adult female rats were split into 4 groups. First, an intramuscular injection (i.m) of BLM (30 mg/m(2)) was administered to BLM and BLM + ALA groups except the control and ALA groups on the 1st, 8th and 15th days. The control group received 0.1 mL (i.m) saline on those days. BLM + ALA group received ALA (50 mg/kg) subcutaneously (s.c) for 2 weeks at the same time with BLM injections, and ALA group received ALA s.c for the same period. Ovarian tissues were evaluated by histopathological, stereological, immunohistochemical (StAR, VDAC2, Caspase-3, Bcl-2, and expression levels) and ELISA (AMH serum levels) methods. The vascular areas and collagen density increased in the medulla, and the volumes of medulla, cortex, and total ovary increased in BLM group, whereas these changes decreased in BLM + ALA group. On the other hand, VDAC2 and Caspase-3 expressions decreased, StAR and Bcl-2 expressions increased in BLM group, whereas VDAC2 and Caspase-3 expressions increased, and StAR and Bcl-2 expression levels significantly decreased in BLM + ALA group. Besides, follicle number and AMH levels decreased in the BLM group, but remarkably increased in the BLM + ALA group. We established that ALA may have ameliorative effects on the harmful effects of BLM on ovary.