| Popis: |
Adverse drug reactions are unavoidable risk factors allied with use of modern medicines. First-line anti-tuberculosis drugs (ATDs) contribute to diverse pathological complications lead to severe oxidative stress and cause hepato-renal injury. This study was designed to investigate protective potential of naringenin to limit ATDs (combination of pyrazinamide, ethambutol, isoniazid and rifampicin) induced hepato-renal injury. The dose of ATDs was converted from human dose into rat dose and three different doses (10, 20 and 40 mg/kg) of naringenin was administered conjointly through oral route on alternate days for 8 weeks and every Sunday was a rest day. One-way ANOVA (P≤0.05) followed by Tukey’s post hoc HSD test determined statistical significance. Results indicated significant increase in IL-6, triglycerides, cholesterol, bilirubin but depletion in IGF-1, albumin and glucose in serum after exposure to ATDs. Lipid peroxidation in microsomes and CYP2E1 enzyme activity was also increased significantly whereas, a severe depletion of endogenous antioxidants including GR, GPx and G-6-PDH was observed. Ultra-structural observations of liver and kidney showed marked deviation in plasma membranes of various cellular and sub-cellular organelles. Conjoint treatment of naringenin counteracted ATDs induced toxic manifestations by regulating IL-6, IGF-1, biochemical and ultra-structural integrity in a dose dependent manner. Naringenin also inhibited the depletion of CYP2E1 enzyme as it provided help for biotransformation of ATDs. These findings demonstrated that naringenin provided protection against ATDs induced hepato-renal injury by balancing oxidative stress and inflammation via upregulating antioxidant enzymes. |
