RETRACTION: Indole-3-Carbinol Enhances the Resolution of Rat Liver Fibrosis and Stimulates Hepatic Stellate Cell Apoptosis by Blocking the Inhibitor of κB Kinase α/Inhibitor of κB-α/Nuclear Factor-κB Pathway

Abstract

Hepatic stellate cells (HSC) play a pivotal role in liver fibrosis, and the clearance of activated HSC by apoptosis is associated with the resolution of liver fibrosis. The development of strategies that promote this process in a selective way is therefore important. We evaluated the effects of indole-3-carbinol (I3C), a nutritional component derived from vegetables from the Brassica family, on liver fibrosis and HSC apoptosis. The in vivo therapeutic effects of I3C were monitored in three rat models of liver fibrosis induced by porcine serum, bile duct ligation, or multiple hepatotoxic factors, and its proapoptotic effect and molecular mechanism were studied in vitro in HSC-T6, a rat HSC line. The results showed that I3C treatment significantly reduced the number of activated HSC in the livers of rats with liver fibrosis. In histopathology, I3C reduced hepatocyte degeneration and necrosis, accelerated collagen degradation, and promoted the reversal of liver fibrosis. I3C prescribed to HSC-T6 resulted in morphologic alterations typical of apoptosis and DNA cleavage to a nucleosomal ladder. Moreover, I3C significantly increased the HSC-T6 apoptosis rate and the expression ratio of Bax to Bcl-2. High-throughput protein array analysis indicated that the tumor necrosis factor-␣/nuclear factor-B (NF-B) signal pathway participated in I3C-induced HSC-T6 apoptosis. Western blot and electrophoretic mobilityshift assay confirmed that I3C inhibited the phosphorylation of inhibitor of B kinase ␣ and inhibitor of B-␣ and NF-B DNA binding activity. In conclusion, I3C could promote the reverse process of liver fibrosis in vivo and induce apoptosis of activated HSC in vitro, which indicates the use of I3C as a potential therapeutic agent in liver fibrosis treatment.

Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

“…However, pre-treatment with indole-3-carbinol exerted a marked anti-inflammatory activity, where the levels of pro-inflammatory markers were significantly reduced when compared to the cisplatin group. Several studies had shown that indole-3-carbinol has a marked anti-inflammatory properties in vitro 18 19 as well as in vivo 18 20 21 . Accumulation of platinum was found to play a role in cisplatin-induced nephrotoxicity 46 47 .…”

“…It was shown that indole-3-carbinol has the ability to increase the activity of some anti-oxidant enzymes such as hemoxygenase-1 and glutathione transferase 16 . Besides, several studies had confirmed the anti-inflammatory activities of indole-3-carbinol in a variety of animal models such as aspirin-induced gastric ulcer 17 , liver fibrosis 18 , lipopolysaccharide-induced acute lung injury 19 and high fat diet-induced obesity 20 . In fact, indole-3-carbinol had been found to reduce the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α and NF-kB 18 19 21 .…”

“…Besides, several studies had confirmed the anti-inflammatory activities of indole-3-carbinol in a variety of animal models such as aspirin-induced gastric ulcer 17 , liver fibrosis 18 , lipopolysaccharide-induced acute lung injury 19 and high fat diet-induced obesity 20 . In fact, indole-3-carbinol had been found to reduce the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α and NF-kB 18 19 21 . Also, the expression of cyclooxygenase-2, lipoxygenase and inducible nitric oxide synthase enzymes was significantly reduced by indole-3-carbinol administration 22 23 .…”

Indole-3-Carbinol Inhibits Nasopharyngeal Carcinoma Growth through Cell Cycle Arrest In Vivo and In Vitro

“…The anticancer activity of I3C is also reflected in a number of signal transduction pathways associated with the inhibition of cell growth. Previous studies have evaluated the inhibition effects of I3C on the prosurvival PI3K/Akt[3], [8], [9] and nuclear factor-κB[10] signal transduction pathways. I3C also down-regulates mitogen-activated protein kinases (MAPK) expression[11].…”

Indole-3-Carbinol Inhibits Laryngeal Cancer Growth Through Cell Cycle Arrest

“…In some signal transduction pathways that were associated with the cell growth inhibition, the anticancer activity of I3C is also reflected. the inhibition effects of I3C have been evaluated by previous studies on the PI3K/Akt pathway [2,7,8] and nuclear factor-kB [9] signal transduction pathways. And mitogen-activated protein kinases (MAPK) expression was also been down-regulated by I3C [10].…”