Protective effect of Bu-zhong-yi-qi decoction, the water extract of Chinese traditional herbal medicine, on 5-fluorouracil-induced renal injury in mice

Abstract

Background: Drug-induced renal injury is a serious toxic side effect of 5-fluorouracil (5-FU) treatment. Bu-zhong-yi-qi decoction (BZYQD), a water extract of Chinese traditional herbal medicine, is widely used in Asia as an alternative treatment to reduce the side effects of chemotherapy and also improve cancer survival. However, the mechanism is unknown. This study is designed to investigate the protective effect of BZYQD on 5-FU-induced renal injury in mice.

Methods: Mice were divided into four groups: the control, 5-FU, 5-FU + low, and high BZYQD group. Mice in the three latter groups were administered 5-FU (100 mg/kg/day, intraperitoneally) for six days, and in the 5-FU + low and high BZYQD groups were given BZYQD (1 or 2 g raw herb/kg/day, intragastrically) beginning four days before 5-FU and continuing until the termination of the experiment. The right kidney fixed in formalin for histological examination and the left was homogenized to measure the levels of apoptosis-related proteins and activities of oxidative stress-related biomarkers. Blood samples were collected for measuring renal function-related biochemical indices.

Results: Renal morphology injury, increased urea nitrogen and creatinine concentration, and decreased SOD, CAT, and GSH-Px were all observed in 5-FU-administrated mice. However, BZYQD almost reversed the morphological injury as well as renal function-related indices and antioxidant enzyme activity.

Conclusion: These results suggest that BZYQD inhibits 5-FU-induced renal injury, possibly through the reduction of apoptosis and necrosis in renal tubular epithelial cells via the antioxidant mechanism. Henceforth, BZYQD may be a potential antioxidant against drug-induced oxidative stress.

Keywords: 5-FU; Bu-zhong-yi-qi decoction; antioxidant; apoptosis; renal injury.