Increased homocysteine mediated oxidative stress as key determinant of hepatitis E virus (HEV) infected pregnancy complication and outcome: A study from Northeast India

Tiwari, Diptika; Das, Chandana; Sultana, Rizwana; Kashyap, Natasha; Islam, Mafidul; Bose, Purabi Deka; Saikia, Anup; Bose, Sujoy

doi:10.1016/j.meegid.2021.104882

Cited by 8 publications

(8 citation statements)

References 41 publications

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“…Published data on oxidative stress in HEV infection are very scarce. Some recent studies show that excessive oxidative stress caused by HEV infection is associated poor pregnancy outcomes [ 21 , 22 ]. We think that HEV may serve as “damage” injury, promotes ROS production and then participates in pathogenesis of liver failure.…”

Section: Discussionmentioning

confidence: 99%

Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with HEV-induced liver failure

Wang

Yao

et al. 2022

BMC Gastroenterol

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Background Viral hepatitis E clinically ranges from self-limiting hepatitis to lethal liver failure. Oxidative stress has been shown to mediate hepatic inflammation during HBV-induced liver failure. We investigated whether a biomarker of oxidative stress may be helpful in assessing severity and disease outcomes of patients with HEV-induced liver failure. Methods Clinical data were obtained from patients with HEV-induced acute viral hepatitis (AVH, n = 30), acute liver failure (ALF, n = 17), and acute-on-chronic liver failure (ACLF, n = 36), as well as from healthy controls (HC, n = 30). The SOD and HMGB1 levels were measured in serum by ELISA. HL-7702 cells were cultured and stimulated by serum from HEV-infected patients or by HMGB1; oxidative status was investigated by CellROX and apoptosis was investigated by flow cytometry. Results Patients with HEV-induced liver failure (including ALF and ACLF) showed increased SOD levels compared with HEV-AVH patients and healthy controls. SOD levels > 400 U/mL were associated with a significantly higher risk of mortality in HEV-ALF and HEV-ACLF patients. Serum from HEV-infected patients led to ROS accumulation, HMGB1 secretion, and apoptosis in HL-7702 cells. Antioxidant treatment successfully inhibited HEV-induced HMGB1 secretion, and HMGB1 promoted apoptosis in HL-7702 cells. Conclusion HEV increased oxidative stress in the pathogenesis of HEV-induced hepatic diseases. Early testing of serum SOD may serve as a predictor of both HEV-ALF and HEV-ACLF outcomes. Moreover, development of strategies for modulating oxidative stress might be a potential target for treating HEV-induced liver failure patients.

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Section: Discussionmentioning

confidence: 99%

Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with HEV-induced liver failure

Wang

Yao

et al. 2022

BMC Gastroenterol

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“…A study by Bhatnagar et al found oxidative stress to be present during pregnancies of HEV-infected women by observing reduced glutathione (GSH) levels in pregnant women infected with HEV compared to healthy pregnant controls [ 108 ]. Another recent study from northeast India identified increased levels of homocysteine [ 109 ], an amino acid found to induce production of reactive oxygen species, in pregnant women suffering from HEV infection [ 110 ]. Additionally, a study in primary human brain microvascular endothelial cells (HBMVCs) infected with swine-derived HEV virus suggested ROS accumulation through upregulated expression of NADPH oxidase 4 (NOX4) [ 12 ].…”

Section: Putative Molecular Factors Involved In Hev-mediated Hcc—hallmarks Of Cancermentioning

confidence: 99%

Beyond the Usual Suspects: Hepatitis E Virus and Its Implications in Hepatocellular Carcinoma

Klöhn

Schrader

Brüggemann

et al. 2021

Cancers

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Hepatitis E virus infections are the leading cause of viral hepatitis in humans, contributing to an estimated 3.3 million symptomatic cases and almost 44,000 deaths annually. Recently, HEV infections have been found to result in chronic liver infection and cirrhosis in severely immunocompromised patients, suggesting the possibility of HEV-induced hepatocarcinogenesis. While HEV-associated formation of HCC has rarely been reported, the expansion of HEV’s clinical spectrum and the increasing evidence of chronic HEV infections raise questions about the connection between HEV and HCC. The present review summarizes current clinical evidence of the relationship between HEV and HCC and discusses mechanisms of virus-induced HCC development with regard to HEV pathogenesis. We further elucidate why the development of HEV-induced hepatocellular carcinoma has so rarely been observed and provide an outlook on possible experimental set-ups to study the relationship between HEV and HCC formation.

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“…Defects in methionine and SAM metabolism, either genetic or resulting from low levels of folate or B12, result in the buildup of one or more metabolites, associated with deleterious effects in the body. Of these, hyperhomocysteinemia, defined as excessively high serum homocysteine levels, has been associated with both global and tissue-specific inflammation, as well as deleterious effects on the vasculature and bone [ 82 , 83 , 84 , 85 , 86 , 87 ]. At another stage of the methionine cycle, hypermethionemia, or excessive levels of methionine, is also observed to alter cell proliferation; when artificially induced in culture, activated T cells divide more rapidly [ 88 ].…”

Section: Folate B12 and The Methionine Cyclementioning

confidence: 99%

“…In addition, homocysteine stimulation results in NLRP3 inflammasome activation and resulting cellular stress via TXNIP—this mechanism contributes to homocysteine’s role as a risk factor in renal failure [ 120 ]. The failure to maintain low homocysteine results in increased oxidative stress, particularly in patients with chronic infection, sometimes with dangerous long-term effects; for example, sustained hyperhomocysteinemia can lead to pregnancy complications in hepatitis E patients [ 86 ].…”

Section: Folate B12 and Sam: Links To Tissue-specific Inflammationmentioning

confidence: 99%

The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation

Vaccaro

Naser

2021

Healthcare

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Vitamin deficiency is well known to contribute to disease development in both humans and other animals. Nonetheless, truly understanding the role of vitamins in human biology requires more than identifying their deficiencies. Discerning the mechanisms by which vitamins participate in health is necessary to assess risk factors, diagnostics, and treatment options for deficiency in a clinical setting. For researchers, the absence of a vitamin may be used as a tool to understand the importance of the metabolic pathways in which it participates. This review aims to explore the current understanding of the complex relationship between the methyl donating vitamins folate and cobalamin (B12), the universal methyl donor S-adenosyl-L-methionine (SAM), and inflammatory processes in human disease. First, it outlines the process of single-carbon metabolism in the generation of first methionine and subsequently SAM. Following this, established relationships between folate, B12, and SAM in varying bodily tissues are discussed, with special attention given to their effects on gut inflammation.

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Increased homocysteine mediated oxidative stress as key determinant of hepatitis E virus (HEV) infected pregnancy complication and outcome: A study from Northeast India

Cited by 8 publications

References 41 publications

Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with HEV-induced liver failure

Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with HEV-induced liver failure

Beyond the Usual Suspects: Hepatitis E Virus and Its Implications in Hepatocellular Carcinoma

The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation

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