Effects of Vitamin E on Redox balance in regulating thiol/disulfide homeostasis in sepsis: An antioxidant therapy perspective.

Abstract

<h4>Background</h4>Sepsis, a life-threatening condition resulting from a dysregulated host response to infection, is associated with high mortality and remains a major global health burden. Sepsis is characterized by an imbalance between oxidative stress and inflammation, leading to disruption of thiol-disulfide homeostasis, hematological abnormalities, cytokine dysregulation, and widespread tissue injury.<h4>Methods</h4>An experimental sepsis model was established in thirty-two male Balb-C mice using lipopolysaccharide administration. Animals were randomized into four groups: control, vitamin E, sepsis, and sepsis plus vitamin E. Serum oxidative stress markers, thiol-disulfide parameters, and inflammatory mediators, including C-reactive protein, interleukin-40, and tumor necrosis factor-alpha, were measured. Hematological indices of systemic inflammation were evaluated (Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio), and lung, liver, and kidney tissues were examined histologically using a semi-quantitative scoring system.<h4>Results</h4>Lipopolysaccharide-induced sepsis caused marked disruption of thiol-disulfide balance, characterized by reduced native and total thiol levels, elevated disulfide levels, increased cytokine release, and severe histopathological injury. Vitamin E supplementation restored thiol-disulfide homeostasis, decreased oxidative stress, and attenuated systemic inflammation. In the sepsis plus vitamin E group, serum thiol levels increased significantly, while disulfide levels declined. Interleukin-40 showed a 24.2% reduction and tumor necrosis factor-alpha a 9.8% reduction compared with untreated septic animals. Histopathological analyses confirmed reduced inflammatory cell infiltration, vascular congestion, and tissue degeneration, particularly in the lungs.<h4>Conclusions</h4>Vitamin E demonstrated significant protective effects against sepsis-induced oxidative and inflammatory injury by preserving thiol-disulfide homeostasis and reducing cytokine production. The more pronounced effect on interleukin-40 compared with tumor necrosis factor-alpha suggests selective modulation of inflammatory pathways and highlights interleukin-40 as a potential biomarker and therapeutic target. These findings support vitamin E as a promising adjunctive therapy in sepsis, although further studies are required to define optimal dosing strategies and assess clinical applicability.