Hexavalent Chromium Induced Alteration of Carbohydrate Bioenergetics: A Dose-dependent Study
Objective: This study was conducted to observe the dose-dependent effect of Cr (VI) on certain aspects of carbohydrate metabolism in mice with four different doses, viz., 5 mg/kg, 10 mg/kg, 15 mg/kg and 20 mg/kg b.w., respectively, for 30 days of exposure.
Methods: Blood glucose, glycogen content, and pyruvic acid of liver tissue were determined to evaluate the glycolytic activity. Enzymes such as isocitrate dehydrogenase (IDH), succinate dehydrogenase, and malate dehydrogenase (MDH) activities were measured to determine the tricarboxylic acid cycle function. In addition, nicotinamide adenine dinucleotide (NADH) ubiquinone C oxidoreductase activity was estimated to evaluate the alteration in oxidative phosphorylation pathway with dose-dependent chromium exposure. Total protein, free amino acid nitrogen, and transaminase enzyme activity were also measured.
Results: Chromium exposure caused marked depletion of blood glucose and liver glycogen contents in a dose-dependent manner. The activities of IDH, succinate dehydrogenase, and MDH were significantly altered in a dose-specific manner by chromium exposure. Relevant exhaustion of glycolytic substrates was noted in the form of reduced pyruvate content in hepatocytes following chromium exposure. In addition, the treatment caused elevation of free amino nitrogen associated with depletion of total protein content and elevated transaminase enzyme activities in hepatocytes. Significant alteration of mitochondrial NADH-ubiquinone C oxidoreductase activity was also noted.
Conclusion: By analyzing the observed results, it can be suggested that Cr (VI) exerts hypoglycemic and glycogenolytic effects associated with alteration of citric acid cycle and electron transport pathways in hepatocytes in a dose-specific manner thus resulting in serious alteration in the carbohydrate bioenergetics and mitochondrial energy generation in hepatic cells.
Keywords: Hexavalent chromium, Hypoglycemia, Glycogenolysis, Citric acid cycle, Electron transport chain.
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