Antioxidant, N-acetyl-?-cysteine inhibits the expression of the collagen α2 (I) promoter in the activated human hepatic stellate cell line in the absence as well as the presence of transforming growth factor-β

Antifibrotic Effects of Antioxidant N-Acetylcysteine in a Mouse Model of Human Hypertrophic Cardiomyopathy Mutation

“…Accordingly, treatment with NAC has been shown to abrogate fibrosis induced by transforming growth factor-beta-1 (23). In addition, NAC could suppress expression of the procollagen genes even in the absence of transforming growth factor-beta-1 (23,24). As shown in the present study, treatment with NAC inhibited activation of p44/42, p38, and JNK kinases, important mediators of cell signaling in response to many forms of stress or injury.…”

TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells

“…2A), whereas no elevation of hydrogen peroxide levels was determined after 24 hours. Since basal levels of ROS are already induced in M1-4HSCs compared to quiescent HSCs, as reported by several investigators [20,28-30], TGF-β is obviously able to provide accumulation of hydrogen peroxide in M1-4HSCs. In contrast, M-HTs showed about 40% reduced intracellular hydrogen peroxide content compared to untreated M1-4HSCs (Fig.…”

“…According to the literature, upregulation of ROS due to TGF-β has also been shown in various cell types such as vascular smooth muscle cells [33], hepatocytes [34], fetal lung fibroblasts [35], cardiac fibroblasts [36] and also HSCs [28], most frequently by upregulation of NADPH oxidase activity [33,35-37]. However, the data available for HSCs refer to (i) the activation of quiescent HSCs and (ii) to proportionally short incubation times in comparison to the fibrosis model employed in this study.…”

S-adenosyl-l-methionine inhibits collagen secretion in hepatic stellate cells via increased ubiquitination

“…ROS has been demonstrated to increase transforming growth factor (TGF)-b expression, a potent cytokine mediator of hepatic fibrogenesis (25). Studies utilizing the antioxidant N-acetyl-L-cysteine demonstrated a reduction in TGF-b signalling (30) and a2(I) procollagen mRNA expression in activated HSCs (31). In an in vivo model of alcohol-induced liver fibrosis, SAMe diminished members of the TGF-b signalling cascade (21).…”