Protective effects of cerium oxide nanoparticles in non-alcoholic fatty liver disease (NAFLD) and carbon tetrachloride-induced liver damage in rats: Study on intestine and liver

Abstract

Background and aims: Nanoparticles could represent a therapeutic approach for the treatment of various diseases. It has been reported that cerium oxide nanoparticles (CeO₂ NPs) have potential useful effects. Therefore, we aimed to examine the protective effects of the CeO₂ NPs in two models of liver injury, non-alcoholic fatty liver disease (NAFLD) and carbon tetrachloride (CCl₄)-induced liver fibrosis, in rats.

Methods: In this experimental study, male rats were randomly divided into different experimental groups including: Experiment 1; group1: healthy rats received normal saline, 2: CCl₄ group, 3: CCl₄ + nanoparticle. Experiment 2; group1: healthy rats received chow diet, 2: NAFLD group, 3: NAFLD + nanoparticle. The oxidative stress markers were determined in the liver and intestine. Tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Histopathological changes of liver and intestine were evaluated by light microspore.

Results: Total antioxidant capacity (TAC) and glutathione (GSH) levels significantly decreased, while malondialdehyde (MDA) and total oxidant status (TOS) were significantly increased in the liver, and intestine of the NAFLD and CCl₄ group compared with control rats. However, the use of nanoparticles significantly normalized these markers. The levels of the TNF-α were significantly reduced in the nanoparticle group as compared with NAFLD model and CCl₄-treated rats. CeO₂ NPs also normalized the liver and intestinal histological changes.

Conclusions: Our finding revealed that CeO₂ NPs has potential protective effects by increasing antioxidant activity, and reducing inflammation.

Keywords: Carbon tetrachloride; Cerium oxide nanoparticles; Inflammation; Liver injury; Rats.

Fig. 1

A: Transmission electron microscopy (TEM), B: scanning electron microscope (SEM), and C: X-ray analysis of Cerium Oxide Nanoparticle (CeO₂, 99.97%, 10–30 nm). NanoSany Corporation, Mashhad, Iran.

Fig. 2

Oxidative stress in the intestine of different treated groups. Results are presented as means ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 as compared with Hepatotoxic group (CCl₄ group). ^###P < 0.01 compared with control. Results are expressed as means ± SEM of six rats/group. TOS: total oxidant status, TAC: total antioxidant capacity, MDA: malondialdehyde, GSH: glutathione, NPs: nanoparticles.

Fig. 3

Oxidative stress in the liver of different treated groups. Results are presented as means ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 as compared with Hepatotoxic group (CCl₄ group). ^###P < 0.01 compared with control. Results are expressed as means ± SEM of six rats/group. TOS: total oxidant status, TAC: total antioxidant capacity, MDA: malondialdehyde, GSH: glutathione, NPs: nanoparticles.

Fig. 4

Oxidative stress in the intestine of different treated groups. Results are presented as means ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 as compared with Hepatotoxic group (NAFLD group). ^###P < 0.01 compared with control. Results are expressed as means ± SEM of six rats/group. TOS: total oxidant status, TAC: total antioxidant capacity, MDA: malondialdehyde, GSH: glutathione, NPs: nanoparticles.

Fig. 5

Oxidative stress in the liver of different treated groups. Results are presented as means ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 as compared with Hepatotoxic group (NAFLD group). ^###P < 0.01 compared with control. Results are expressed as means ± SEM of six rats/group. TOS: total oxidant status, TAC: total antioxidant capacity, MDA: malondialdehyde, GSH: glutathione, NPs: nanoparticles.

Fig. 6a

TNF-α levels in different treated groups. Results are presented as means ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 as compared with Hepatotoxic group. ^###P < 0.01 compared with control. Results are expressed as means ± SEM of six rats/group TNF-α: tumor necrosis factor-α, NPs: nanoparticles. b. TNF levels in different treated groups. Results are presented as means ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 as compared with NAFLD group. ^###P < 0.01 compared with control. Results are expressed as means ± SEM of six rats/group TNF-α: tumor necrosis factor-α, NPs: nanoparticles.

Fig. 7

Histological analysis of intestine and liver section in different treated groups stained with H&E. A: healthy rats, B: healthy rats received nanoparticle C: CCl₄ received rats, D: CCl₄ received rats received nanoparticle. Liver section of hepatotoxic (CCl₄) group shows abnormal hepatic structure with vacuolization, necrosis, mild hemorrhage, moderate inflammation, cell hyperplasia, cell infiltration and apoptosis. Liver section of treated animals restored morphological alterations. Original magnification 100 × .

Fig. 8

Histological analysis of intestine and liver section in different treated groups stained with H&E. A: healthy rats, B: healthy rats received nanoparticle, C: NAFLD group, D: NAFLD rats received nanoparticle. Furthermore, the NAFLD rats showed hepatic steatosis with ballooning degeneration, inflammatory cell infiltration, and lipid droplet accumulation. Treatment with nanoparticle normalized all of these alterations. Original magnification 400 × .