Cytoprotective Epigenetic and DNA-Damage Repair Molecular Mechanisms of α-Lipoic Acid (ALA) Against Carbon Tetrachloride Induced Hepatotoxicity and Neurotoxicity in Rats

Introduction: Carbon tetrachloride (CCl₄), is industrial solvent, hose living close to textile and chemical factories are exposed to CCl₄ and are at great risk. The toxic effect of CCl₄ is believed to be due to trichloromethyl radicals (CCl₃^•) which causes extensive membrane molecular and mitochondrial damages, and ultimately cell death by necrosis and ammonia toxicity. Many common medications cause hepatotoxicity and neurotoxic chemicals including ethanol also cause OS in the brain.

Aim: The aim of this present study was to determine whether administration of α-lipoic acid, a potent iron-chelating antioxidant ergogenic aid could decrease CCl₄-induced hepatotoxicity and neurotoxicity.

Materials & Methods: Male albino rats (4-months old, 250 gm body wt) were pretreated with α-lipoic acid (Started 3-days prior to CCl₄ administration) (ALA:100mg/Kg b.wt, orally via an oral cannula for 11 days), followed by oral ingestion with the CCl₄ (CCl₄ in Olive oil, 1.6 mL/kg b.wt). At the end of the 11-days, the animals were sacrificed and biological samples were collected for the estimation of biomarkers of liver dysfunction, biomarkers of OS and inflammation in the brain.

Results: Application of α-lipoic acid mitigated the toxic onslaught of CCl₄-induced-toxicity and exerted hepatoprotective effects by significantly (p<0.001) reducing SGOT, SGPT, ﻻ-GT, bilirubin, MDA, 8- OHdG, IL-6, TNF-α, XO, NOS, NADPH-oxidase and augmentation of serum total protein, A/G ratio. Further, ALA protects the liver and brain by increasing antioxidants such as GSH, SOD, Catalase, GST, GPx, GR, G6PD, spares ATP, DNA and modulation of PARP-1.

Conclusion: Knowledge of the epigenetic and molecular mechanisms involved in the CCl₄-induced hepatotoxicity in this model is the key to identifying potential therapeutic targets for liver dysfunction associated with a variety of hepatic disorders including alcoholic cirrhosis and brain dysfunction due to ammonia toxicity.