Oxidative stress—A key determinant of complications and negative outcome in hepatitis E virus infected pregnancies: A comprehensive account involving cases from northeast India

Abstract

Regulated oxidative stress (OS) is important during pregnancy. Sporadic studies suggest the significance of deregulated OS in hepatitis E virus (HEV) infected pregnancy, but with limited reactive oxygen species (ROS) or antioxidant markers. The present novel study, therefore, aimed to evaluate the significance of ROS‐antioxidant imbalance and resulting altered OS in HEV infected pregnancy complications like preterm delivery (PTD) and outcome. Difference in serum levels of ROS and antioxidant panel of markers were evaluated by ELISA for HEV immunoglobulin M RNA positive genotype 1 cases (including acute [acute viral hepatitis, AVH] and fulminant [fulminant hepatic failure, FHF] cases) and healthy term delivery subjects, and analyzed statistically. Direct ROS marker H2O2 levels and indirect OS marker for DNA damage 8‐hydroxy‐2′‐deoxyguanosine was significantly increased in HEV‐cases compared to controls, and was associated and prognostic factor for PTD and fetal death in HEV cases. A comparatively lower total serum antioxidant capacity was observed in the FHF cases compared to the control subjects and the AVH cases. Glutathione (GSH) levels and superoxide dismutase (SOD) activity were significantly associated with PTD in the FHF sub‐cohorts (p = 0.017) and AVH sub‐cohorts (p < 0.001), respectively, and was associated with poor prognosis in HEV cases. The serum H2O2 levels were found to be negatively correlated with SOD activity (p = 0.016) and GSH levels (p = 0.001) in the HEV‐AVH cases; and positively correlated with the viral load in HEV cases (p = 0.023). The ROS‐antioxidant imbalance resulting OS plays a detrimental associative role in HEV infected pregnancy complications like PTD and adverse pregnancy outcomes; and holds therapeutic significance.

Oxidative stress and disruption of the antioxidant defense system as triggers of diseases

“…NO-produces the NO-synthase enzyme. There are three types of NO-synthase (NOS) isozymes in mammals including endothelial NO-synthase, neuronal NO-synthase, and inducible NO-synthase (Kashyap et al, 2023).…”

“…The components of the antioxidant protection system are considered to be: electron acceptors -vitamins E and K 3 ; acceptors of superoxide radical anions -methionine, cysteine; scavengers of hydroxyl radicals -aliphatic alcohols; factors of elimination of toxic products of LPO tocopherol (TF), ionol, superoxide dismutase, glutathione peroxidase system; metal chelators with variable valence (complexons). Components of antioxidant protection are divided into hydrophilic and hydrophobic, enzymatic (catalase, superoxide dismutase, glutathione peroxidase system, glutathione, ascorbic acid, adrenaline, serotonin, tocopherols, retinoids, flavonoids, phospholipids, ceruloplasmin) and non-enzymatic (Kashyap et al, 2023).…”

The Role of Glutathione in Selected Viral Diseases

“…HEV infection aggravates oxidative stress during pregnancy [163]. Lower GSH levels are observed in pregnant women with an HEV infection having preterm delivery and low birthweight newborns compared to healthy pregnant women [143,144]. It is suggested that the GSH level may be used for risk stratification in HEV infection during pregnancy [163].…”