Ameliorating and Protective Potential of Chitosan against Thioacetamide- Induced Hepatotoxicity in Male Albino Rats

Abstract

Chitosan, a natural product derived from chitin, has attracted much attention as a promising therapeutic material, owing to its unique biological activities. This study was designed to explore the possible improving potential of chitosan, as a safe natural marine product on liver regeneration and to evaluate the correlation between the hypolipidemic effect and the anti-oxidant activity of chitosan in thioacetamide (TAA)-induced toxicity in male Wistar rats. Fifty adult male wistar rats were divided into 5 groups. Group (1) was the control group. Group (2) was TAA group in which the rats were intraperitoneally injected with thioacetamide (300 mg/kg b. wt) once for induction of liver toxicity, group (3) chitosan group received diet containing 5% chitosan daily for 14 days, group (4) was the chitosan then thioacetamide group in which animals were received daily diet containing 5% chitosan for 14 days, then they were intraperitoneally injected with thioacetamide at a dose of 300 mg/kg b. wt once and group (5) was the thioacetamide then chitosan group, animals of this group were intraperitoneally injected with thioacetamide at a dose of 300 mg/kg b.wt once then treated with chitosan in a diet containing 5% chitosan daily for 14 days. Functions of the liver (ALAT, ASAT, GGT, ALP, albumin) and kidney (urea and creatinine), serum lipid profile, liver tissue levels of reducedglutathione (GSH), nitric oxide (NO), malondialdehyde (MDA) using conventional spectrophotometric techniques was done. Besides, measurement of the plasma pro-inflammatory cytokine TNF-α using ELISA technique were achieved. TNF-α, Survivin and c-Myc quantitative gene expression analysis using QRT- PCR in liver tissue was determined. In addition to, histopathological investigation of liver tissue sections was carried out. The thioacetamide group showed significant elevation in the values of ALAT, ASAT, GGT, ALP, urea and creatinine, and deteriorated serum lipid profile pattern, decreased liver GSH level and increased hepatic NO and MDA levels. However, chitosan then thioacetamide and thioacetamide then chitosan groups showed significant improvement in these values to near the normal values. Moreover, TAA group showed a significant reduction in albumin levels which was elevated to near normal levels upon chitosan treatment. The correlation and linear regression analyses revealed a negative correlation among glutathione level and serum cholesterol, LDL-cholesterol and triglycerides levels. However, NO was positively correlated with total cholesterol, LDL-cholesterol and triglycerides levels. TAA treatment significantly reduced survivin gene expression levels (-65%) as compared to normal control group. Besides, c-myc gene expression showed a significant elevation by chitosan both as protective and curative treatments (300 % &700%, respectively). Regarding the plasma TNF- α level and its gene expression, it was significantly elevated (368.3%) in TAA group. This elevation was significantly reduced as compared to TAA group in both chitosan then thioacetamide and thioacetamide then chitosan groups (-66.5%&-57.3%, respectively).The histopathological examination revealed a better ameliorative pattern of the chitosan protective group. This study indicated the promising action of chitosan in liver regeneration. Also, it showed anti inflammatory effect as it reduced the level of TNF-α, both at gene and protein levels. Whereas, chitosan increased the gene expression of c-myc which is enhancer of cell proliferation.