Valproate-Induced Liver Injury: Modulation by the Omega-3 Fatty Acid DHA Proposes a Novel Anticonvulsant Regimen

• DOI: 10.1007/s40268-014-0042-z
• Publication Date: 2014-04-14T07:31:50Z
• Authors: Marwa A. Abdel-Dayem; Ahmed A. Elmarakby; Azza A. Abdel-Aziz; Chelsey Pye; Shehta A. Said; Abdalla M. El-Mowafy
• Keywords: Aspartate transaminase; Lipid peroxide

The polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, modulate its anticonvulsant effects, then sought cellular and molecular basis such actions. Lastly, also verified whether may kinetically alter plasma levels/clearance rate VPA.VPA (500 mg/kg orally for 14 days in rats) evoked prominent hepatotoxicity that appeared as a marked rise (2- 4-fold) serum hepatic enzymes (γ-glutamyl transferase [γ-GT], alanine aminotransferase [ALT], alkaline phosphatase [ALP]), increased lipid peroxide (LPO) tumor necrosis factor-alpha (TNFα) levels, well myeloperoxidase (MPO) activity (3- 5-fold), lowering albumin (40 %), depletion liver reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed hepatocellular degeneration, replacement by inflammatory cells, focal pericentral necrosis, micro/macrovesicular steatosis. Concurrent treatment with (250 mg/kg) markedly blunted elevated levels enzymes, peroxides, TNFα, MPO activity, while raising GSH levels. alleviated most cytologic insults linked VPA. Besides, pentylenetetrazole (PTZ) mouse convulsion model, latency VPA, beyond their individual responses. pharmacokinetic studies joint administration did not VPA concentrations.DHA substantially ameliorated injury induced boosted pharmacologic effects. manipulated definite machinery curb oxidative stress inflammation, without affecting Collectively, these protective synergy profiles propose superior VPA-drug combination regimen.