Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study

Iran J Basic Med Sci. 2017 Dec;20(12):1297-1305. doi: 10.22038/IJBMS.2017.9567.


Objectives: Arsenic, a toxic metal in drinking water and butyric acid (BA) is a free fatty acid found in many foods. These two can induce oxidative stress in some tissues. The present study investigated the protective effect of metformin against toxicity induced by Arsenic (As) and BA in isolated mice liver mitochondria and pancreatic islets.

Materials and methods: In this study, liver mitochondria were isolated by adopting different centrifugation methods and pancreatic islets isolated by a collagenase method. Mitochondria were incubated by BA (75 μM), As (100 μM) and metformin (0, 0.5, 1, 3, 10 mM) and the islets also incubated by BA (1000 μM), As (100 μM) and metformin (0, 1, 3, 10 mM) for 1 hr. At the end of study, mitochondrial viability (MTT), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), malondial- dehyde (MDA), glutathione (GSH) and islets insulin secretion were measured employing specific relevant methods.

Results: As and BA significantly increased ROS, MDA and ΔΨm levels and decreased GSH level, succinate dehydrogenase activity and insulin secretion. On the other hand, pretreatment with metformin, returned mitochondrial complex II activity, reduced ROS, MDA and ΔΨm levels and increased GSH level and insulin secretion of pancreatic islets.

Conclusion: As and BA in combination or in isolation induce oxidative stress in liver mitochondria and decrease insulin secretion of pancreatic islets. Metformin has a protective effect probably caused by its antioxidant feature. The findings suggest the potential role of metformin in mitochondria therapy and insulin secretion in many diseases.

Keywords: Arsenic; Butyric acid; Islet insulin secretion; Liver mitochondrial; Metformin; Oxidative stress.