Bone marrow mononuclear cells boosts anti-cytogentical aberration effect of N-acetylcysteine and α-lipoic acid in rat’s liver and bone marrow: implication of oxidative and inflammatory pathways

Abstract

This study investigates the hepatoprotective effect of bone marrow mononuclear cells (BM-MNCs) transplantation, N-acetylcysteine (NAC) and α-lipoic acid (ALA). Rats were administrated carbon tetrachloride (CCl4) (1 mg/kg, i.p.) twice/week for 8 weeks for the induction of hepatotoxicity. 7 groups of rats were used as follows: Normal control, CCl4, CCl4 co-administered with BM-MNCs (1 × 106 in 0.1 ml PBS, i.v.), or NAC (300 mg/kg, p.o) or ALA (100 mg/kg, p.o) single or combination. Liver function was tested by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin as well as interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (Gpx), superoxide dismutase (SOD) and catalase (CAT) activities in liver homogenates. Besides that, estimation of DNA damage was performed. In addition to Micronucleus test and histopathological investigation. CCl4 treated rats showed elevation in ALT, AST, TNF-α, IL-6 and MDA accompanied by reduction in ALB, IL-10, SOD, CAT, GPx and TAC and increased the number of DNA breaks in liver tissue, showed many micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow. NAC, ALA, BM-MNCs and their combination caused a reduction of ALT, AST, while, increase albumin, CAT, TAC, GPx, SOD as compared to CCl4 treated groups. Also decrease in MDA, IL-6 and TNF-α concurrently with an increase in IL-10. Moreover, BM-MNCs, NAC, ALA, and their combination decreased DNA tail %, and the count of MnPCEs. BM-MNCs combination with NAC or ALA exerted significant antioxidant, anti-inflammatory and anti-cytogenetical aberrations effect compared to each of them alone. Highlights CCl4 elevated ALT, AST, TNF-α, IL-6 and MDA CCl4 reduced ALB, IL-10, SOD, CAT, GPx and TAC CCl4 increased the number of DNA breaks in liver NAC, ALA and BM-MNCs reduced ALT, AST, while, increase albumin, CAT, TAC, GPx, SOD NAC, ALA and BM-MNCs decreased in MDA, IL-6 and TNF-α and increased IL-10