45 JCHR (2020) 10(1), 45-56 Journal of Chemical Health Risks www.jchr.org ORIGINAL ARTICLE Cumulative Effect of Mesenchymal Stem Cells and Heme Oxygenase-1 Inducer in Ameliorating Induced Liver Toxicity in Rats Ahmed Talaat Abd Elaziz *1 , Hanaa Mohamed Elzahed 2 , Sahar Hassan Ahmed 3 , Bahaa Eldin A. Khaled 4, 5 , Eman H. Nadwa 6, 7 1 Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt 2 Forensic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt 3 Lab Technology Department, Faculty of Applied Medical Science, Misr University For Science &Technology, Cairo, Egypt 4 Department of Anatomy, College of Medicine, Jouf University, Jouf, Arab Saudi 5 Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt 6 Department of Pharmcology and Therapeutics, College of Medicine, Jouf University, Jouf, Arab Saudi 7 Department of Medical pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt (Received: 23 October 2019 Accepted: 18 December 2019) KEYWORDS MSCs; Liver fibrosis; HO-1 inducer; HO-1 inhibitor ABSTRACT: Liver diseases are most commonly occurring nowadays, that’s why we are in argent need to develop new strategies in treatment. to evaluate the role of MSCs in regenerating liver cells and to clarify the anti- inflammatory role of HO-1 either alone or as a combined therapy with MSCs. 72 rats were divided into seven groups (n=10 rats/group) as follows, group1: control rats, group 2: CCL 4 , group 3: CCL 4 that received MSCs group 4: CCL 4 that received HO-1 inhibitor, group 5: CCL 4 that received HO-1 inducer, group 6: CCL 4 that received combined MSCs and HO-1 inhibitor , and group 7: CCL 4 that received combined MSCs and HO-1 inducer. All groups were evaluated histopathologically with assessment of liver functions. The combined MSCs and HO-1 inducer group showed the highest significant results in ALT (p-value ˂0.05), albumin (p-value ˂0.05), HO-1 activity (p-value ˂0.0001), and genes expression compared to other groups. This is due to the cumulative anti-inflammatory role of both MSCs and HO-1 together with the ability of MSCs to increase the HO-1 expression with further reduction in inflammation and fibrosis. MSCs and HO-1 inducer provide promising tool in treatment of liver disease. INTRODUCTION Liver cell injury occurs as a result of alcoholic consumption, nonalcoholic fatty liver disease, HCV infection. Chronic inflammation causes excessive accumulation of extra cellular matrix (ECM) by activated hepatic stellate cell (HSC) among the hepatocytes with subsequent liver fibrosis [1, 2] . *Corresponding author: mc_maadico@yahoo.com (A. T. Abd Elaziz) DOI: 10.22034/jchr.2020.1881598.1058