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Rimonabant Improves Oxidative/Nitrosative Stress in Mice with Nonalcoholic Fatty Liver Disease
Bojan Jorgačević1, Dušan Mladenović1, Milica Ninković2
1Institute of Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Abstract:
The present study deals with the effects of rimonabant on oxidative/nitrosative stress in high diet- (HFD-) induced experimental nonalcoholic fatty liver disease (NAFLD). Male mice C57BL/6 were divided into the following groups: control group fed with control diet for 20 weeks (C; n = 6); group fed with HFD for 20 weeks (HF; n = 6); group fed with standard diet and treated with rimonabant after 18 weeks (R; n = 9); group fed with HFD and treated with rimonabant after 18 weeks (HFR; n = 10). Daily dose of rimonabant (10 mg/kg) was administered to HFR and R group by oral gavage for two weeks. Treatment induced a decrease in hepatic malondialdehyde concentration in HFR group compared to HF group (P < 0.01). The concentration of nitrites + nitrates in liver was decreased in HFR group compared to HF group (P < 0.01). Liver content of reduced glutathione was higher in HFR group compared to HF group (P < 0.01). Total liver superoxide dismutase activity in HFR group was decreased in comparison with HF group (P < 0.01). It was found that rimonabant may influence hepatic iron, zinc, copper, and manganese status. Our study indicates potential usefulness of cannabinoid receptor type 1 blockade in the treatment of HFD-induced NAFLD.
Insights
Rimonabant treatment reduced oxidative stress and improved antioxidant markers in mice with diet-induced nonalcoholic fatty liver disease (NAFLD). This suggests cannabinoid receptor type 1 blockade may be a potential therapy for NAFLD.
Area of Science:
- Hepatology
- Pharmacology
- Biochemistry
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a growing health concern.
- High-fat diets (HFD) are a primary driver of NAFLD.
- Oxidative and nitrosative stress are key pathological mechanisms in NAFLD.
Purpose of the Study:
- To investigate the effects of rimonabant on oxidative/nitrosative stress in a HFD-induced NAFLD mouse model.
- To evaluate rimonabant's impact on key biochemical markers of liver damage and antioxidant status.
Main Methods:
- Male C57BL/6 mice were fed a control or HFD for 20 weeks.
- Rimonabant (10 mg/kg) was administered orally for the final two weeks to specific groups.
- Hepatic malondialdehyde, nitrites/nitrates, reduced glutathione, and superoxide dismutase activity were measured.
Main Results:
- Rimonabant treatment significantly decreased hepatic malondialdehyde and nitrite/nitrate concentrations in HFD mice.
- Reduced glutathione levels were elevated, and superoxide dismutase activity was decreased by rimonabant in HFD mice.
- Rimonabant also influenced hepatic levels of iron, zinc, copper, and manganese.
Conclusions:
- Cannabinoid receptor type 1 blockade with rimonabant shows potential in mitigating oxidative stress in HFD-induced NAFLD.
- Rimonabant may offer a therapeutic strategy for managing NAFLD by targeting key stress pathways.
- Further research is warranted to explore rimonabant's full therapeutic potential in NAFLD.
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