Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats

Abstract

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models.

Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100 mg/kg, 10 days), multiple dose Mtx group (Mtx 1 mg/kg 1, 3, 5, 7 days) and Mtx and ALA group (Mtx 1 mg/kg 1, 3, 5, 7 days and ALA 100 mg/kg, 10 days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated.

Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count.

Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.

Chinese abstract

探讨氨甲喋呤(Mtx)对卵巢存在的潜在氧化损伤并评估α-硫辛酸（ALA）对氧化应激模型的有效性。

将32只雌性Wistar-albino大鼠随机分为4组, 对照组, α-硫辛酸组（ALA 100 mg/kg, 10 天）, 高剂量Mtx组（Mtx 1 mg/kg 1,3,5,7天）以及Mtx和ALA组（Mtx 1 mg/kg 1, 3天, 5天, 7天, ALA 100 mg/kg, 10天）。评估血清总抗氧化状态（TAS）, 总氧化状态（TOS）和氧化应激指数（OSI）, 肿瘤坏死因子-α（TNF-α）, 组织丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶 （CAT）、抗Mullerian激素（AMH）以及总卵泡数量。

Mtx导致TAS显著降低, TOS、OSI、MDA水平的显著增加以及GSH-Px和CAT活性降低。另外Mtx组促炎细胞因子(TNF-a)量增加, AMH 值和总卵泡数明显降低。然而, ALA治疗能逆转生化结果、AMH 值以及总卵泡量。

α-硫辛酸可改善甲氨蝶呤诱导的大鼠卵巢氧化损伤。

Keywords:

• Alpha lipoic acid
• methotrexate
• ovarian reserve
• oxidative stress

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. The study was not supported.