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

Gynecol Endocrinol. 2017 Aug;33(8):653-659. doi: 10.1080/09513590.2017.1306847. Epub 2017 Mar 31.

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.

Keywords: Alpha lipoic acid; methotrexate; ovarian reserve; oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Mullerian Hormone / blood
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antioxidants / therapeutic use*
  • Biomarkers / blood
  • Dietary Supplements
  • Female
  • Folic Acid Antagonists / administration & dosage
  • Folic Acid Antagonists / adverse effects*
  • Infertility, Female / chemically induced
  • Infertility, Female / metabolism
  • Infertility, Female / pathology
  • Infertility, Female / prevention & control*
  • Lipid Peroxidation / drug effects
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Nucleic Acid Synthesis Inhibitors / administration & dosage
  • Nucleic Acid Synthesis Inhibitors / adverse effects
  • Ovarian Reserve / drug effects*
  • Ovary / drug effects
  • Ovary / immunology
  • Ovary / metabolism
  • Ovary / pathology
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats, Wistar
  • Thioctic Acid / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimetabolites, Antineoplastic
  • Antioxidants
  • Biomarkers
  • Folic Acid Antagonists
  • Nucleic Acid Synthesis Inhibitors
  • Tumor Necrosis Factor-alpha
  • Thioctic Acid
  • Anti-Mullerian Hormone
  • Methotrexate