Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1

Context: Acetaminophen (APAP) is an analgesic and antipyretic agent commonly known agent to cause hepatic and renal toxicity at a higher dose. Naringin, a bioflavonoid possesses multiple pharmacological properties such as antioxidant, anti-inflammatory, analgesic and anti-hyperlipidemic activity. Objective: To evaluate the effect of naringin against the APAP-induced hepatic and renal toxicity. Materials and methods: Male Wistar albino rats (180-220g) were divided into various groups, and toxicity was induced by APAP (700mg/kg, p.o., 14days). Naringin (20, 40 and 80mg/kg, p.o.) or Silymarin (25mg/kg) was administered to rats 2h before APAP oral administration. Various biochemical, molecular and histopathological parameter were accessed in hepatic and renal tissue. Results: Naringin pretreatment significantly decreased (p<0.05) serum creatinine, blood urea nitrogen, bilirubin, aspartate transaminase, alanine transaminase, lactate dehydrogenase, low-density lipoprotein, very low-density lipoprotein, cholesterol and triglycerides as compared with APAP control rats. Decreased level of serum albumin, uric acid, and high-density lipoprotein were also significantly restored (p<0.05) by naringin pretreatment. It also significantly restores (p<0.05) the altered level of superoxide dismutase, reduced glutathione, malondialdehyde and nitric oxide in hepatic and renal tissue. Moreover, altered mRNA expression of hepatic farnesoid X receptor and renal injury molecule-1 (KIM-1) were significantly restored (p<0.05) by naringin treatment. Naringin treatment also reduced histological alteration induced by APAP in the liver and kidney. Conclusion: Naringin exerts its hepato- and nephroprotective effect via modulation of oxido-nitrosative stress, FXR and KIM-1 mRNA expression.