Novel protection by Omega-3-FAs (DHA or EPA) against carbamazepine's liver-injury: differential suppression of oxidative-stress and inflammatory markers, and the influence on carbamazepine-clearance

• DOI: 10.1016/j.nutos.2022.01.006
• Publication Date: 2022-01-29T19:05:30Z
• Authors: Abdalla M. El-Mowafy; Azza A. Abdel-Aziz; Marwa A. Abdel-Dayem
• Keywords: Oxidative-stress; 0106 biological sciences; Carbamazepine; Nutrition. Foods and food supply; Liver-injury; Cytokines; Clearance; TX341-641; Omega-3-FAs; 01 natural sciences; 3. Good health

PurposeCarbamazepine (CBZ)-evoked liver-injury is multifaceted and can be serious. Specific drug-antidote versus CBZ's hepatotoxicity has been absent. The effects of omega(ω)-3-FAs (Eicosapentaenoic acid, EPA, Docosahexaenoic DHA), on CBZ-toxicity, possibly-involved mechanisms, have remained unknown. Here, we investigated whether and, how then, two-ω-3-FAs (DHA/EPA) may alleviate hepatotoxicity, relieve the disrupted organelles liver, possibly alter CBZ-plasma levels.MethodsRats were treated with CBZ (100 mg/kg orally, daily) for 1-2-weeks in presence-and-absence DHA (EPA). Biochemical-markers (ALT, Albumin, ALP, γ-GT), oxidative-stress (MDA, GSH, TAC) inflammation (IL-6, TNF-α, CRP) assessed at one-week-intervals. Further, pharmacokinetic-studies plasma-CBZ levels, with/without co-administered-ω-3-FAs, immunoassays. Liver-histopathological sections examined correlated functional biochemical-markers.Resultseither ω-3-FAs, or a rank-order potency, significantly abolished all liver injury-markers, inflammation. Kinetic-immunoassays revealed no interaction serum-CBZ-levels. However, EPA significantly-increased CBZ-level than control. Histopathological-studies only minimal portal DHA. also, elicited additional degenerative-changes surrounding hepatocytes.Conclusionsω-3-FAs mitigated CBZ-induced liver-toxicity by suppressing inflammation, without altering its clearance, (DHA). evoked rise levels inferior-liver protection Histopathological assessment showed ω-3-FAs to also protect liver-integrity organelles, thereby implying fruitful therapeutic-regimen CBZ.