The protective effects of naringin against cisplatin-induced pulmonary toxicity in rats: Insights into the modulation of ER stress and SIRT1/Nrf2 pathway

Abstract Background Cisplatin (CIS) is a chemotherapeutic agent which is frequently utilised in the treatment of ovarian, breast, testicular and lung cancer. Nevertheless, the potential for severe and irreversible toxicity to the lungs restricts its utilisation. Naringin (NRG), a flavanone glycoside found in significant quantities in citrus fruits, has been demonstrated to exert protective effects against oxidative tissue damage. The present study aimed to assess the protective effect of NRG against CIS-induced pulmonary toxicity. Methods The administration of NRG (50 and 100 mg/kg) was conducted orally over a period of seven days. CIS (7.5 mg/kg, IP) was administered on day 2 to rats, and lung samples were collected on day 8. Results The CIS application induced lipid peroxidation (LPO), inflammation, and endoplasmic reticulum stress (ERS) in the lung, resulting in the emergence of histopathological findings. However, the administration of NRG was found to be capable of preventing lung injury by suppressing LPO, inflammation and ERS levels in a dose-dependent manner. Furthermore, the suppression of CIS-induced sirtuin1(SIRT1)/nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling was abolished by NRG supplementation. Conclusions The present study has shown, for the first time, that NRG has a potential for protection against lung injury by modulating SIRT1/Nrf2/HO-1 signalling in the context of CIS-induced lung injury.