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

Keywords:

• Hepatotoxicity
• oxidative stress
• fibrosis
• hepato-protective agent
• mutagenicity testing

Acknowledgments

The authors are grateful to Dr. Laila Ahmed Rashed, Professor of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, for her help in isolation of bone marrow cells, Dr. Adel Bakeer Kholoussy, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University, for examining and interpreting histopathological aspects of this study, and Dr. Karima Fathy Mahrous, Professor of Molecular Genetics, Cell Biology Department, National Research Center for her generous help in cytogenetical aberration assessment and active collaboration in the laboratory work of this thesis. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure statement

No potential conflict of interest was reported by the author(s).