Dan Liu - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Changlin Zhen - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Xiuzhen He - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
wansong chen - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Juan Pan - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Mengying Yin - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Mengru Zhong - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Hongyan Zhang - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Xiaohuan Huang - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China
Yonghui Zhang - Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing ۴۰۴۱۲۰, China

Objective(s): Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF’s hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity. Materials and Methods: Fifty female ICR mice were randomly divided into ۵ groups: Control, GEF (۲۰۰ mg/kg), NG (۵۰ mg/kg) + GEF (۲۰۰ mg/kg), NG (۱۰۰ mg/kg) +GEF (۲۰۰ mg/kg), NG (۲۰۰ mg/kg) +GEF (۲۰۰ mg/kg). After ۴ weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected. Results: The results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase۳, and Poly (ADP-ribose) polymerase ۱ (PARP۱) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes. Conclusion: In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF’s toxicity to the liver.

Apoptosis, Autophagy, gefitinib, Hepatotoxicity, Naringin