Induction of pancreatic thiol proteins by zinc protect against diabetogenic, oxidative and histological changes produced by arsenic toxicity in rats

ABSTRACT

Recent studies reported that, chronic arsenic exposure is always associated with an increase in the prevalence of diabetes mellitus. It is recognized that arsenic contributes to oxidative stress in several organs and systems including the islets of Langerhans through generation of reactive oxygen species [ROS]. So the current study was undertaken to elucidate the possible role of zinc as an antioxidant in the protection against diabetes mellitus induced by arsenic. Male Sprague-Dawley rats were given sodium arsenite daily at a dose of 1.5 mg/kg by gavage for 60 consecutive days. Another group of rats were injected I.P with zinc chloride 20 mg/kg for 2 days with one day interval, then was given sodium arsenite at a dose of 1.5 mg/kg by gavage every day for 60 consecutive days. Blood samples and pancreatic tissue specimens were collected from all the tested groups at the end of the experiment for biochemical evaluation and histological examination. The level of both thiobarbituric acid reactive substances [TBARs] and nitric oxide [NO] were significantly elevated in arsenite treated group as compared to control group. Hyperglycemia, hyper-insulinemia and low insulin sensitivity was observed. The activity of pancreatic thioredoxin reductase [TrxR] was lower than control group. Also, the levels of metallothionein [MT] and total glutathione [GSH] in pancreas increased significantly relative to the control group indicating the presence of stress and oxidative damage, respectively. Histological sections of pancreas of arsenic treated rats showed that a large number of islets were shrunken with low number of islet cells .The number of beta-cells decreased relative to the total islet cell number compared to control. Pre-treatment with zinc chloride before arsenic administration reversed the previous biochemical parameters and histological changes. The pancreatic TBARs and NO are reduced compared with arsenite treated group. Significant decrease in glucose level and decrease the level of insulin with increase insulin sensitivity was observed. Also pre-treatment with zinc resulted significant increase in the activity of TrxR, levels of MT and GSH. Zinc chloride prevented the reduction in beta-cell and islet cell number. Also it could restore the normal morphology of the islets. The current results clearly indicate the beneficial effects of zinc chloride in both controlling hyperglycemia and the protection of the pancreatic islet cells against oxidative stress in diabetes through induction of thiol proteins which may help setting a new direction toward the development of effective treatment of diabetes mellitus