Citric Acid Administration Protects Against Insulin-Induced Hypoglycemic Brain and Liver Injury

Abstract

We aimed to investigate the effect of treatment with citric acid on oxidative stress and tissue injury in brain and liver of rats subjected to hypoglycaemia. Rats received intraperitoneal injections of insulin (5 IU/kg) followed 30 min later by oral administration of saline or citric acid at doses of 0.2, 0.4 or 1 g/kg. Rats were euthanized 1 h after insulin injection and their brains and livers were dissected out for biochemical studies including determination of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), paraoxonase-1 (PON-1), 5-lipoxygenase, and cholinesterase. Serum alanine aminotransferase and aspartate aminotransferase were determined and histological investigations for the liver were carried out. Results indicated that in insulin only treated rats, MDA and NO levels were significantly increased whereas GSH content and PON-1 activity significantly decreased in brain and liver tissue. In addition, cholinesterase activity significantly decreased while 5-lipoxygenase increased in brain with respect to the saline control group after insulin injection. Serum aminotransferases showed significant elevation in insulin-treated rats together with distorted hepatic architecture, hydropic degeneration, and extensive cytoplasmic vacuolation of hepatocytes. The biochemical alterations in the brain and liver of hypoglycaemic rats were markedly alleviated in a dose-dependant manner by the administration of citric acid which also markedly reduced the histological liver injury with the group treated with insulin and citric acid at 1 g/kg exhibiting more or less preserved hepatic architecture. These results indicate that citric acid was effective in alleviating the biochemical alterations in brain and liver and protecting against liver injury during hypoglycaemia. It could thus prove of benefit in patients on insulin therapy with accidental hypoglycaemia from over dosing.