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. 2015:2015:842108.
doi: 10.1155/2015/842108. Epub 2015 May 11.

Rimonabant Improves Oxidative/Nitrosative Stress in Mice with Nonalcoholic Fatty Liver Disease

Bojan Jorgačević  1 , Dušan Mladenović  1 , Milica Ninković  2 , Milena Vesković  1 , Vesna Dragutinović  3 , Aleksandar Vatazević  4 , Danijela Vučević  1 , Rada Ješić Vukićević  5 , Tatjana Radosavljević  1
Affiliations

Rimonabant Improves Oxidative/Nitrosative Stress in Mice with Nonalcoholic Fatty Liver Disease

Bojan Jorgačević et al. Oxid Med Cell Longev. 2015.

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.

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Figures

Figure 1
Figure 1
The effects of control chow and high fat diet on food intake during 20 weeks of treatment (C, HF, R, and HFR). Statistical significance of the difference was estimated by using one-way analysis of variance (ANOVA) with Tukey's post hoc test (∗ P < 0.05 versus first 18 weeks; ∗∗ P < 0.01 versus first 18 weeks; ## P < 0.01 versus control group).
Figure 2
Figure 2
The effect of rimonabant on the level of malondialdehyde (MDA) in the mice liver after 20 weeks feeding with high fat and control chow diet (a). The effect of rimonabant on the NOx (nitrites + nitrates) in the mice liver after 20 weeks feeding with high fat and control chow diet (b). Statistical significance of the difference was estimated by using one-way analysis of variance (ANOVA) with Tukey's post hoc test (∗ P < 0.05, ∗∗ P < 0.01 versus C, and ## P < 0.01 versus HF).
Figure 3
Figure 3
The effect of rimonabant on total SOD, Cu/ZnSOD, and MnSOD activity in the liver after 20 weeks feeding with high fat and control chow diet. Statistical significance of the difference was estimated by using one-way analysis of variance (ANOVA) with Tukey's post hoc test (∗ P < 0.05,∗∗ P < 0.01 versus C, and ## P < 0.01 versus HF).
Figure 4
Figure 4
The effect of rimonabant on the GSH content in the mice liver after 20 weeks feeding with high fat and control chow diet. Statistical significance of the difference was estimated by using one-way analysis of variance (ANOVA) with Tukey's post hoc test (∗ P < 0.05, ∗∗ P < 0.01 versus C, and ## P < 0.01 versus HF).
Figure 5
Figure 5
The effect of HF diet on histopathological changes in the liver. HE-stained preparations were sectioned with blade thickness of 5 μm and analyzed and photographed using a combined photobinocular light microscope Olympus BX51. (a) Control with normal liver histology /10x/; (b) rimonabant treated control chow diet fed group with normal liver histology /10x/; (c) liver histology in HF group shows mild steatosis with portal inflammatory infiltrate and focal necrotic changes in parenchyma /20x/; (d) liver histology in HFR group shows mild steatosis /10x/.
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