Protective effects of curcumin, α-lipoic acid, and N-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats

Abstract

Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl(4))-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl(4) fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl(4)-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.

The protective effect of N-acetyl cysteine against carbon tetrachloride toxicity in rats

“…5), aggregations of inflammatory cells and marked inflammatory changes associated with fatty changes (Fig.6), focal necrotic areas, congestion and pyknotic nuclei were also observed (Fig.7). These observations agree with Manjrekar, Jisa, Bag, and Adikary (2008); Morsy et al (2012); Morakinyo, Oludare, Anifowose, and Adegoke (2012); Domitrovic et al (2015);and Hismiogullari et al (2015). Masson trichrome stained sections showed congested thickened portal tract with dense fibrous tissues radiating from the portal vein and extending into the parenchyma (Fig.…”

“…Also, Wang et al (2014 reported that NAC was able to ameliorate oxidative stress and cytotoxicity in HepG cells. Additionally, Morsy, Abd Alla, Mahmoud, Abdel Wahab, and Mahmoud (2012) showed that curcumin, α-lipoic acid and NAC caused a significant decrease of hepatic MDA levels as compared to CCL4 fibrotic rats. However, results revealed insignificant change in serum total protein in all groups as compared to control; this was context with Hanafi (2012).…”

“…8). Conversely, liver sections from animals Values are given as mean ± SD (n = 6) a Significant compared with control at P < 0.05 b Significant compared with control at P < 0.01 c Significant compared with control at P < 0.001 The effects of CCl4 were prevented completely or partially by NAC antioxidant activity as it prevented the increase in lipid peroxidation products (Manibusan, Odin, & Eastmond, 2007;Morsy et al, 2012 andDemiroren et al, 2014). The development of CCl4-induced liver fibrosis is usually associated with oxidative stress and lipid peroxidation (Manibusan et al, 2007).…”

The role of curcumin in liver diseases

“…In these models, curcumin showed a major role as an inhibitor of HSC activation; it also seems to be able to reduce liver damage, as well as the a-SMA and procollagen expression in the liver, when administered in CCl 4 -induced liver fibrosis models for 4-8 weeks. The recognized mechanism of action in those models included curcumin's ability to target multiple sites, such as platelet-derived growth factor-b receptor (PDGF-bR) [37], matrix metalloproteinases (MMPs) [37,38], tissue growth factor b (TGFb) [39,40], peroxisome proliferator-activated receptors (PPARc) [41], toll-like receptors (TLRs) [42], apoptotic pathway [43,44], inflammatory cytokines [41,42,45,46] and microRNAs [47,48]. Recently, curcumin's capacity to increase cyclic adenosine monophosphate levels, which leads to an increase in the number of mitochondrial DNA duplicates, has been demonstrated [49].…”

“…When this balance is broken by hyperactivation of HSCs, fibrosis occurs. Available evidence showed that curcumin plays a role in downregulation of TIMP-1 and TIMP-2 in vivo [38,[71][72][73] and in vitro [74], while it upregulates MMP-2 [73], MMP-7 [72], MMP-9 [73] and MMP-13 [38,72]. This leads to inhibition of HSC activation due to the degradation of one of the main components of the ECM, the fibrillar collagens.…”