Protection of naringenin against 5-fluorouracil toxicity in the liver

Abstract

Drugs used in cancer treatment eliminate cancer cells but also have toxic effects on healthy cells. The study aims to determine the protective effect of the antioxidant naringenin (NAR) against the harmful effects of 5-fluorouracil (5-FU) used in cancer treatment on the liver. A total of 28 Sprague-Dawley male rats were divided into four groups (n = 7) as control, 5-FU, NAR and 5-FU + NAR. 150 mg/kg 5-FU was administered intraperitoneally to the 5-FU and 5-FU + NAR groups. 100 mg/kg NAR was administered to the NAR and 5-FU + NAR groups via a gavage catheter. At the end of the experiment, biochemical analyses performed on the blood serum taken from the animals showed that 5-FU increased the levels of liver oxidative stress markers. Aspartate aminotransferase (AST), high-density lipoprotein (HDL), total cholesterol (TG), alanine aminotransferase (ALT), triglycerides (CH) levels increased in the blood (p < 0.05). It was found that glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels decreased and malondialdehyde (MDA) levels increased in liver tissue due to the effect of 5-FU (p < 0.03). It was also confirmed that the situation was normalized as a result of the combined application of 5-FU and NAR. Histopathological examinations showed that 5-FU caused karyopyknosis and microvesicular steatosis in hepatocytes. Immunohistochemical examinations showed that 5-FU increased the expression of caspase 3 and TNF-α in the liver. NAR, which has antioxidant, antiapoptotic and anti-inflammatory effects, largely prevented the pathological formations that developed with 5-FU application. According to the results of the study, NAR was shown to protect against the harmful effects that may occur in the liver during treatment with 5-FU.