Treatment of Chronic Hepatitis C Virus Infection via Antioxidants

Melhem, Alla; Stern, M.; Shibolet, Oren; Israeli, Eran; Ackerman, Zvi; Pappo, Orit; Hemed, Nilla; Rowe, Mina; Ohana, Hana; Zabrecky, George; Cohen, Robert M.; Ilan, Yaron

doi:10.1097/01.mcg.0000174023.73472.29

Cited by 121 publications

(89 citation statements)

References 41 publications

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“…Previous studies suggested that LA acts as an antiinflammatory agent in vivo and plays a role in cardiovascular protection (27)(28)(29), although LA's mechanism of action remained unclear. Our results suggest a mechanism by which LA activates the PI3K/Akt signaling pathway and consequently inhibits NF-B activity, expression of proinflammatory mediators, and septic lethality.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to playing an important role in mitochondrial energy metabolism, LA and dihydrolipoic acid can scavenge reactive oxygen species, regenerate physiological antioxidants, chelate metal ions, and stimulate insulin signaling (23)(24)(25). Lipoic acid significantly improves diabetic neurovascular and metabolic abnormalities (26) and may play a role in cardiovascular protection and as an antiinflammatory agent (27)(28)(29)(30). Using cultured human aortic endothelial cells, we have shown that LA inhibits TNF␣-or LPS-induced expression of CAMs and MCP-1 and subsequent monocyte-endothelial interactions (11).…”

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confidence: 99%

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α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway

Zhang

Wu²,

Hagen³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

230

174

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, heart, and aorta. Lipoic acid also improved survival of endotoxemic mice. All of these antiinflammatory effects of LA were abolished by treatment of the animals with wortmannin. We conclude that LA inhibits LPS-induced monocyte activation and acute inflammatory responses in vitro and in vivo by activating the PI3K/Akt pathway. Lipoic acid may be useful in the prevention of sepsis and inflammatory vascular diseases.inflammation ͉ NF-B ͉ sepsis ͉ endothelial activation ͉ monocytes

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway

Zhang

Wu²,

Hagen³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

230

174

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show abstract

“…In this regard, it should be noted that oxidative and nitrosative stress may possess diverse effects on cell growth and apoptosis [108]. As a consequence, antioxidants have been proposed as an adjunct therapy for chronic hepatitis C [109].…”

Section: Viral Hepatitis and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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“…These lignans are abundant in the seeds and fruits of SC (Huang et al, 2007;Ikeya et al, 1979;Lu et al, 2009;Panossian et al, 2008;Slanina et al, 1997). Previous studies have shown that SC possesses neuroprotective effects on glutamate-induced apoptosis (Lee et al, 2012) and has the ability to protect the liver from injury induced by toxins substances, such as, those associated with hepatitis (Liu, 1989;Melhem et al, 2005). Schizandrin B and C are components of SC extract (Xu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Kim

Lee

Park

et al. 2014

Pharmaceutical Biology

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Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells. Materials and methods: SCE concentrations from 100 to 400 mg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.Results: SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 mg/ml and 87.3% ± 7.6% at 400 mg/ml at 24 h and by 40.2% ± 5.3% 100 mg/ml and 95.3% ± 1.3% 400 mg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 mg/ml and 370.2% ± 7.2% at 400 mg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 mg/ml and 311.5% ± 6.1% at 400 mg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death. Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

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Treatment of Chronic Hepatitis C Virus Infection via Antioxidants

Abstract: These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.

Cited by 121 publications

References 41 publications

α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway

α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway

Role of free radicals in liver diseases

Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

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