MYRICETIN REDUCES CISPLATIN-INDUCED LUNG INJURY BY REGULATING OXIDATIVE STRESS AND HYPOXIA INDUCIBLE FACTOR-1α LEVELS

Cisplatin is an anticancer agent that is frequently used in the treatment of solid tumors. However, widespread organ toxicity is the most important factor limiting its use. Lung toxicity has also become an increasing concern in recent years. This study aimed to evaluate the protective roles of myricetin, a natural antioxidant found in plants, in cisplatin-induced lung injury. For this purpose, twenty-eight male Wistar rats were randomly assigned to four equal groups (n=7): control, myricetin, cisplatin, and myricetin+cisplatin. The control group received physiological saline; the myricetin group was given myricetin (10 mg/kg) intraperitoneally for seven consecutive days. The cisplatin group was given a single dose of cisplatin (7.5 mg/kg) intraperitoneally on the seventh day. The myricetin+cisplatin group was treated with myricetin for seven consecutive days, and at the end of the seventh day, cisplatin was administered. One day later, the rats were sacrificed, and their lungs were removed. The sections obtained from the lungs were stained with hematoxylin & eosin, and histopathological damage was evaluated. Biochemical analyses were performed using total oxidant status, total antioxidant status, and hypoxia-inducible factor-1α. In results, significant inflammatory cell infiltration, cellular deterioration, and loss of tissue integrity were observed in the cisplatin group. In contrast, in the myricetin+cisplatin group, the cellular structure and alveolar order were largely preserved, and inflammatory infiltration was minimal. Pretreatment with myricetin reduced total oxidant status and hypoxia-inducible factor-1α while increasing total antioxidant status levels. Taken together, this study indicates that pretreatment of myricetin could serve therapeutic purposes in cisplatin-induced lung injury.