International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2016.851.862ZakariaSarah MahmoudAmr A.A. HasanRehab A. MahmoudMona F. El FayoumiHassan M. 82016128Background and Objective: Acute Hepatic Failure (AHF) is associated with a high mortality rate. Toll-like receptors (TLRs) have been implicated in different liver diseases, however, their role in the pathogenesis of carbon tetrachloride (CCl4)-induced acute liver injury has not been extensively studied. Therefore, the present study was conducted to investigate the protective effect of cinnamaldehyde (CIN), a natural product that possesses anti-inflammatory and anti-oxidant properties, against acute hepatic injury. Materials and Methods: Liver injury was induced by CCl4 /olive oil mixture (1:1, v/v) at a dose of 280 μL/100 g b.wt., once daily for 3 days followed by a dose of 140 μL/100 g b.wt., once daily for the following 3 days by oral gavage. Rats were treated with CIN (10 mg kg1 day1, p.o.) or silymarin (SIL, 100 mg kg1 day1, p.o.) for 6 consecutive days starting from the first day. Results: Cinnamaldehyde significantly reversed CCl4-induced elevation in serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities and bilirubin level (p<0.05). Further, CIN significantly reduced CCl4-induced oxidative stress and inflammation mediated through TLR4 signaling pathway including myeloid differentiation factor (MyD) 88-dependent and toll/interleukin-1 receptor domain-containing adaptor inducing interferon-beta (TRIF)-dependent pathways, as well as the expression of downstream transcription factors such as nuclear factor-kappa B. The protective effect of CIN was comparable to that of SIL. Conclusion: The results show that CIN may be a therapeutic alternative to SIL for the protection of acute liver injury via inhibition of inflammation mediated through TLR4 signaling cascade. 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