Gallic Acid Alleviates Methotrexate‐Induced Oxidative Ovarian Damage in Rats
Abstract
Although methotrexate (MTX) is an effective chemotherapeutic agent in the treatment of cancer, its use is limited due to the occurrence of systemic tissue toxicity, including those affecting the reproductive system. Gallic acid (GAL) is a phenolic compound that has been demonstrated to exert beneficial effects in a number of pathological conditions associated with oxidative stress (OS) in recent years. This study was designed to investigate the potential therapeutic benefits of GAL in the treatment of MTX-induced ovarian damage, for the first time. Adult female rats (n=30) were randomly allocated to five groups: control, MTX, MTX+GAL (2.5 and 5 mg/kg) and high-dose GAL only (5 mg/kg). A single intraperitoneal injection of MTX (20 mg/kg) was administered to induce ovarian toxicity. The treatment groups were administered 2.5 and 5 mg/kg of GAL intraperitoneally for a period of three consecutive days. The levels of OS, inflammation and apoptosis were determined in ovarian tissue samples collected on the fifth day of the study using spectrophotometric methods. The results showed that GAL treatment reduced the level of ovarian lipid peroxidation, inflammation, and apoptosis and promoted the ovarian antioxidant system in rats subjected to MTX. The results of this study indicate that GAL may have the potential to ameliorate MTX-associated oxidative and inflammatory ovarian damage. The ovarian protective effect of GAL requires further confirmation through more extensive preclinical studies.
Keywords
Apoptosis, Gallic acid, Inflammation, Methotrexate, Ovarian damage, Oxidative stress, Rat model
Ethical Statement
This study was approved by the Local Animal Research Ethics Committee of Karadeniz Technical University (Protocol no: 2023/07) and performed according to the animal research reporting of in vivo experiments (ARRIVE) guidelines.
Thanks
The authors wish to thank Sait Al and Ibrahim Aydin from Surgical Practice and Research Center of Karadeniz Technical University for professional assistance with the experimental studies.
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