Manifold hepatoprotective actions of α-lipoic acid on metabolic function through redox regulation, inflammatory modulation, and anti-apoptosis after chronic sleep-deprived injury

TL;DR

Alpha-lipoic acid protects the liver from sleep deprivation-related damage by reducing inflammation and restoring metabolic function.

Contribution

This study demonstrates the hepatoprotective effects of alpha-lipoic acid against chronic sleep deprivation-induced dysfunction.

Findings

ALA reduces serum AST, ALT, and ALP levels and stabilizes hepatic Fe2+ intensity.

ALA decreases inflammatory markers like NF-κB, TNF-α, and IL-6 while increasing antioxidant enzymes.

ALA suppresses apoptosis and ferroptosis by modulating BAX, Bcl-2, GPx4, and FACL4 activities.

Abstract

Chronic sleep deprivation (CSD) is a major public health issue that causes metabolic dysfunction by disrupting redox homeostasis and triggering hepatic inflammation. Given the strong anti-oxidative and anti-inflammatory properties of alpha lipoic acid (ALA), this study aims to determine whether exogenous ALA supplementation would provide hepatoprotection and therefore, maintain the metabolic activity following CSD.

Adult male Wistar rats were randomly assigned to three groups (n = 6/group). The first two groups underwent three cycles of 5-day total sleep deprivation followed by 2-day rest, receiving daily 2 mL olive oil (CSD group) or ALA (100 mg/kg in 2 mL olive oil) (CSD + ALA group), respectively. The third group received no treatment serving as yoked control (CSC group). Spectrometric, biochemical, immunoblot, and immunohistochemical analyses were performed to assess the hepatic redox-active Fe2+ intensity, metabolic function, anti-oxidative enzyme expression, and the pro-inflammatory cytokine levels.

ALA significantly improves metabolic function as effectively attenuates serum concentrations of AST, ALT, and ALP, and stabilize hepatic Fe2+ intensity. ALA also remarkably decreases the protein level of inflammatory factors including NF-κB, TNF-α, IL-6, IL-1β, and cyclooxygenase-2 (COX2), as well as increases the expression of Nrf2-induced antioxidative enzymes such as SOD1 and glutathione peroxidase (GPx). Moreover, ALA further suppresses apoptosis and ferroptosis by modulating related markers including BAX, Bcl-2, GPx4, and FACL4 activities.

These findings clearly demonstrate that ALA confers manifold hepatoprotective effects against CSD-induced dysfunction by significantly restoring redox balance, decreasing hepatic inflammation, suppressing apoptotic and ferroptotic signaling, thereby successfully preserving metabolic activity.

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