L-Carnitine ameliorates the liver by regulating alpha-SMA, iNOS, HSP90, HIF-1alpha, and RIP1 expressions of CCL4-toxic rats

Document Type : Original Article


1 Department of Histology-Embryology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

2 Department of Biology, Faculty of Science, Erciyes University, Kayseri, Turkey

3 Department of Biochemistry, Faculty of Medicine, Erciyes University, Kayseri, Turkey

4 Department of Pathology, Faculty of Veterinary, Erciyes University, Kayseri, Turkey


Objective(s): Carbon tetrachloride (CCL4) toxicity triggers fibrosis, activating various mechanisms within the cell. We aimed to create damage with CCL4 and investigate the effectiveness of L-carnitine on the mechanisms we identified.
Materials and Methods: Forty rats were divided into 5 groups with equal number of rats in each group. Group I: Control group, Group II: L-carnitine group, 200 mg/kg L-carnitine twice a week, Group III: CCL4 group, 0.2 ml/100 gr CCL4, IP, dissolved in olive oil 2 times a week during 6 weeks; Group IV: L-carnitine + CCL4 group, 200 mg/kg L-carnitine 24 hr before 0.2 ml/100 g CCL4 application twice a week; Group V: CCL4 + L-carnitine, 200 mg/kg L-carnitine half an hour after 0.2 ml/100 g CCL4 application. The liver was evaluated histologically. Immunohistochemically stained with α-SMA, iNOS, HSP90, HIF-1α, and RIP1. TNF-α, TGF-β, AST, ALT, ALP, and GGT measurements were evaluated.  
Results: In the classical lobule periphery, an increase in lipid accumulation and a decrease in glycogen accumulation were observed. After immunohistochemical measurements and biochemical analyzes, an increase in the expression density of all proteins was observed in group III. In group IV and V, an improvement in tissue and a decrease in protein expression densities were observed.
Conclusion: iNOS serves as a free radical scavenger in response to damage caused by increased toxicity of α-SMA, HSP90, and HIF-1α. Especially, increased RIP1 level in the tissue indicates the presence of necrosis in the tissue after CCL4-toxicity. Supplementing the amount of endogenous L-carnitine with supplementation provides a significant improvement in the tissue.


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