Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
General Authority for Hospitals and Educational Institutes- Ministry of Health, Cairo, Egypt.
Toxicol Mech Methods. 2021 Jul;31(6):437-449. doi: 10.1080/15376516.2021.1906370. Epub 2021 Apr 28.
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 (CCl) (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, CCl, CCl co-administered with BM-MNCs (1 × 10 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. CCl 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 CCl 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.HighlightsCCl elevated ALT, AST, TNF-α, IL-6 and MDACCl reduced ALB, IL-10, SOD, CAT, GPx and TACCCl increased the number of DNA breaks in liverNAC, ALA and BM-MNCs reduced ALT, AST, while, increase albumin, CAT, TAC, GPx, SODNAC, ALA and BM-MNCs decreased in MDA, IL-6 and TNF-α and increased IL-10 [Figure: see text].
本研究探讨了骨髓单核细胞（BM-MNCs）移植、N-乙酰半胱氨酸（NAC）和α-硫辛酸（ALA）的肝保护作用。大鼠每周两次腹腔注射 1mg/kg 的四氯化碳（CCl）8 周，诱导肝毒性。使用以下 7 组大鼠：正常对照组、CCl 组、CCl 联合 BM-MNCs（1×10 在 0.1ml PBS 中，iv）、NAC（300mg/kg，po）或 ALA（100mg/kg，po）单一或联合。通过测量血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和白蛋白以及白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）、总抗氧化能力（TAC）、谷胱甘肽过氧化物酶（Gpx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）在肝匀浆中的活性来检测肝功能。此外，还进行了 DNA 损伤的评估。除微核试验和组织病理学检查外。CCl 处理的大鼠显示 ALT、AST、TNF-α、IL-6 和 MDA 升高，同时 ALB、IL-10、SOD、CAT、GPx 和 TAC 降低，肝组织中 DNA 断裂增加，骨髓中出现许多多色性红细胞微核（MnPCEs）。与 CCl 处理组相比，NAC、ALA、BM-MNCs 及其组合降低了 ALT、AST，同时增加了白蛋白、CAT、TAC、GPx、SOD。同时降低 MDA、IL-6 和 TNF-α，同时增加 IL-10。此外，BM-MNCs、NAC、ALA 及其组合降低了 DNA 尾%，并减少了 MnPCEs 的数量。与单独使用 NAC 或 ALA 相比，BM-MNCs 与 NAC 或 ALA 的联合使用具有更显著的抗氧化、抗炎和抗细胞遗传畸变作用。
