Attenuation of Experimental Cholesterol Gallstone Formation by Manganese Chloride in Mice: Role of Nfκβ Pathways

Abstract

Manganese (Mn) a trace element, has been documented to exert important role in the metabolism of cholesterol. Cholesterol gallstone (CG) pathogenesis is directly linked to biliary cholesterol imbalance which could be due to diabetes complication or mis-management. NF-κB pathway, an inflammatory regulator has been implicated in metabolic disease especially during diabetes and gallstone. However, management of cholesterol gallstone due to diabetes with trace element is vague. This study investigates the probable role of Manganese during cholesterol gallstone formation due to diabetes complications. 80 Female Swiss mice were grouped thus: I (control), II (Untreated-CG), III and IV (normal mice treated 0.37mg/kg and 0.74mg/kg Mn respectively), V and VI (CG treated 0.37mg/kg and 0.74mg/kg Mn respectively), and VII and VIII (CG treated 75mg/7kg and 350mg/kg aspirin respectively). Experimental CG was induced with cholesterol-rich diets after alloxan-induced diabetes. On sacrifice, blood collected was evaluated for complete haematological analysis and biochemistry while excised liver was assayed for biochemical variables. Results were subjected to one-way ANOVA values were expressed as Mean ± SEM and significant at p ≤ 0.05. Manganese treatment significantly increased packed cell volume, RBC count and haemoglobin with decreased platelet and leukocyte counts, liver enyzmes (AST, ALT and ALP), BUN and creatinine levels in CG groups compared with untreated-CG. Blood glucose, plasma Low Density Lipoproteins and liver malodialdehyde levels were significantly reduced while Liver nitric-oxide, sulfhydryl and glutathione levels increased significantly in Manganese-treated groups compared with untreated-CG. Manganese significantly increased feacal iron contents in normal mice by the 2nd week. Hepatocytes and gallbladder histology appear normal in Manganese-treated groups. Liver NF-Kβ immunoreactivity was downregulated in Manganese-treated CG groups. Manganese attenuated experimental hyperglycemia induced cholesterol gallstone by ameliorating liver oxidative stress and NF-Kβ inflammatory pathway.