Sinapic Acid Attenuate Liver Injury by Modulating Antioxidant Activity and Inflammatory Cytokines in Thioacetamide-Induced Liver Cirrhosis in Rats

Abstract
Abstract: Sinapic acid (SA) is a natural pharmacological active compound found in berries, nuts, and\r\ncereals. The current study aimed to investigate the protective effects of SA against thioacetamide\r\n(TAA) fibrosis in rats by histopathological and immunohistochemical assays. The albino rats (30)\r\nwere randomly divided into five groups (G). G1 was injected with distilled water 3 times/week\r\nand fed orally daily with 10% Tween 20 for two months. G2–5 were injected with 200 mg/kg\r\nTAA three times weekly for two months and fed with 10% Tween 20, 50 mg/kg silymarin, 20, and\r\n40 mg/kg of SA daily for 2 months, respectively. The results showed that rats treated with SA had\r\nfewer hepatocyte injuries with lower liver index (serum bilirubin, total protein, albumin, and liver\r\nenzymes (ALP, ALT, and AST) and were similar to that of control and silymarin-treated rats. Acute\r\ntoxicity for 2 and 4 g/kg SA showed to be safe without any toxic signs in treated rats. Macroscopic\r\nexamination showed that hepatotoxic liver had an irregular, rough surface with micro and macro\r\nnodules and histopathology expressed by Hematoxylin and Eosin, and Masson Trichrome revealed\r\nsevere inflammation and infiltration of focal necrosis, fibrosis, lymphocytes, and proliferation bile\r\nduct. In contrast, rats fed with SA had significantly lower TAA toxicity in gross and histology and\r\nliver tissues as presented by less liver tissue disruption, lesser fibrosis, and minimum in filtered\r\nhepatocytes. Immunohistochemistry of rats receiving SA showed significant up-regulation of HSP\r\n70% and down-regulation of alpha-smooth muscle actin (-SMA) protein expression compared to\r\npositive control rats. The homogenized liver tissues showed a notable rise in the antioxidant enzymes\r\n(SOD and CAT) actions with significantly lower malondialdehyde (MDA) levels compared to that of\r\nthe positive control group. Furthermore, the SA-treated rats had significantly lower TNF-a, IL-6, and\r\nhigher IL-10 levels than the positive control rats. Thus, the findings suggest SA as a hepatoprotective\r\ncompound due to its inhibitory effects on fibrosis, hepatotoxicity, liver cell proliferation, up-regulation\r\nof HSP 70, and downregulation of -SMA expression, inhibiting lipid peroxidation (MDA), while\r\nretaining the liver index and antioxidant enzymes to normal.

Author
Mustafa AbdulMonam Zainel

DOI
https://doi.org/10.3390/biomedicines11051447

Publisher
biomedicines

ISSN

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