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Surgery and Acute Stress Decrease NRF2 mRNA Expression and Promote Iron Metabolism Alteration, Oxidative Stress, and Inflammatory Gene Expression in the Liver of Prehypertensive Rats
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Surgery and Acute Stress Decrease NRF2 mRNA Expression and Promote Iron Metabolism Alteration, Oxidative Stress, and Inflammatory Gene Expression in the Liver of Prehypertensive Rats
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Surgery and Acute Stress Decrease NRF2 mRNA Expression and Promote Iron Metabolism Alteration, Oxidative Stress, and Inflammatory Gene Expression in the Liver of Prehypertensive Rats
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Journal Article
Surgery and Acute Stress Decrease NRF2 mRNA Expression and Promote Iron Metabolism Alteration, Oxidative Stress, and Inflammatory Gene Expression in the Liver of Prehypertensive Rats
2025
Overview
This study investigated how non-hepatic surgery and subsequent acute stress affect iron distribution, redox state, antioxidant defence, and inflammation-related gene expressions and iron metabolism in the liver of borderline hypertensive rats. We used air-jet stress as a model of acute psychological stress (3 sessions of 5 sec. air-jet) applied approximately 22 hours post-surgery (carotid artery and jugular vein cannulation). Both the surgery (Su) and post-surgical stress (Su+Str) increased corticosterone and reduced iron concentrations in plasma, while increasing remanent magnetisation (Mr) and coercivity (Hc) in whole blood. In the liver, Su and Su+Str reduced mRNA expressions of genes encoding NFR2 and GPX4 proteins (Nfe2l2 and Gpx4, respectively), and induced a significant increase in hepatic conjugated dienes, proinflammatory factors (Il1b) and iron-regulating genes mRNA (Hmox1, Fpn1, Fth1, Hamp, Tfr1), despite elevated Hmox1 and Sod1 mRNA expressions. In addition, hepatic Mr and Hc after Su and Su+Str were elevated, suggesting a qualitative change of iron-containing substances in circulation and liver tissue. In addition, in the Su+Str group, the elevated saturation magnetisation (Ms) is indicative of elevated total iron content. These findings suggest that a mild non-hepatic surgery may reduce hepatic mRNA expression of NRF2 and GPX4, which was associated with oxidative tissue damage accompanied by qualitative alterations in cellular iron, indicating a pro-ferroptotic state that, together with enhanced inflammation, may contribute to post-surgical liver injury. Additionally, the combination of surgery and acute post-surgical stress led to tissue iron accumulation, which may contribute to liver damage.
