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

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-03-21 DOI:10.1002/jbt.70230

Nese Colcimen, Seda Keskin

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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/m²) 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.

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评估硫辛酸对博来霉素诱导的卵巢毒性的保护作用

在癌症治疗过程中使用化疗药物可能会导致卵巢卵泡耗竭，进而导致育龄患者不孕。我们旨在确定博莱霉素（BLM）对大鼠卵巢的毒性作用，并评估α-硫辛酸（ALA）对博莱霉素毒性的保护作用。我们将30只成年雌性大鼠分成4组。首先，除对照组和 ALA 组外，BLM 组和 BLM + ALA 组在第 1、8 和 15 天肌肉注射 BLM（30 mg/m2）。对照组在这些天接受 0.1 mL（i.m）生理盐水。BLM + ALA 组在注射 BLM 的同时皮下注射 ALA（50 毫克/千克），为期 2 周；ALA 组在同一时期皮下注射 ALA。卵巢组织通过组织病理学、立体学、免疫组化（StAR、VDAC2、Caspase-3、Bcl-2和表达水平）和ELISA（AMH血清水平）方法进行评估。BLM组髓质的血管面积和胶原密度增加，髓质、皮质和整个卵巢的体积增大，而这些变化在BLM + ALA组中有所减少。另一方面，BLM组VDAC2和Caspase-3表达量减少，StAR和Bcl-2表达量增加，而BLM + ALA组VDAC2和Caspase-3表达量增加，StAR和Bcl-2表达量明显减少。此外，BLM组的卵泡数和AMH水平下降，而BLM + ALA组明显上升。我们认为ALA可能对BLM对卵巢的有害影响有改善作用。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.