Attenuation of cisplatin-induced oxidative ovarian injury by usnic acid in rats through inhibition of inflammation and endoplasmic reticulum stress

Abstract

Despite its effectiveness as a DNA intercalator in the treatment of numerous cancers, cisplatin (CIS) exerts deleterious effects on healthy cells, including those that function in reproductive organs. Usnic acid (UA) is a dibenzofuran derivative that is naturally present in lichens and is widely employed in traditional medicine on account of its antioxidant and analgesic activity. The current study aimed to evaluate the therapeutic potential of UA in counteracting CIS-induced ovotoxicity. The experiments comprised five groups of 6 rats each, which were categorised as follows: control, UA (10 mg/kg), CIS (5 mg/kg), CIS + UAs (5 and 10 mg/kg). Subsequent to the conclusion of the experimental procedures, the serum and ovarian tissues collected were subjected to biochemical and histopathological analysis. The results revealed that the CIS administration led to the suppression of the antioxidant system, which resulted from the depletion of the reduced glutathione (GSH) pool within the ovarian tissue. Furthermore, the administration of CIS was found to induce lipid peroxidation (LPO), inflammation, and endoplasmic reticulum stress (ERS). Conversely, UA treatments following CIS administration led to a substantial reduction in LPO levels by means of regeneration of the intracellular GSH pool. Furthermore, the administration of UA treatments resulted in the suppression of inflammatory and ERS processes, which was achieved via modulation of the Nrf2 pathway. Furthermore, the chemoprotective potential of UA was confirmed by serum anti-mullerian hormone levels and histological analysis. Consequently, UA may be considered as a potential chemotherapy-supporting molecule that can protect ovarian tissue following CIS chemotherapy.