It is believed that oxidative stress plays an important role in a number of diseases including inflammatory conditions, atherosclerosis. Hyperglycaemia results in generation of ROS and increases oxidative stress, thus perpetuating the development of late diabetic complications. The aim of the present study was to investigate the mechanisms of modification of antioxidant enzymes and enzymes of the pentose phosphate pathway, which supply reducing equivalents in the cell, under oxidative stress in vivo and in vitro. Hypoclorous acid is an effective biological oxidant produced by activated neutrophils. HOCl plays a role of the major inflammation mediator in mammalian tissues. HOCl (100-1000 mM) in vitro inhibited considerably in a dose-dependent manner the activity of the enzymes of the pentose phosphate pathway in the rat liver postmitohondrial fraction. HOCl at a concentration of 100 nmol/mg protein inhibited transketolase activity by 65±5%, glucose-6-phosphate dehydrogenase - by 50±5% and 6-phosphogluconate dehydrogenase - by 55±5%. The activities of glutathione peroxidase and catalase slightly decreased. On the contrary, in the rat heart postmitohondrial fraction HOCl (100-1000 mM) inhibited considerably catalase, increased glutathione peroxidase activity and decreased significantly the activity of the key enzymes of the pentose phosphate pathway. The inhibition of the pentose phosphate pathway enzymes was accompanied by oxidation of intracellular reduced glutathione, oxidative protein modification (protein carbonyl group accumulation, mixed protein-glutathion disulphides and chloramine formation), and membrane lipid peroxidation. The sensitivity of rat heart cell components to oxidative damage by HOCl was higher in comparison with that of the liver.

In our study long-term STZ-induced hyperglycaemia (9 weeks) markedly reduced the activities of the antioxidative enzymes, GSHPx (by 26%) and catalase (by 34%), the activity of GST (by 38%) catalyzing the reaction of detoxification of electrophilic/oxidizing drugs and the activity of G6PDH (by 27%). Blood glucose, glycated haemoglobin, as well as plasma ALT and AST activities increased in rats with streptozotocin-induced experimental diabetes. Otherwise, we did not observe increased accumulation of membrane lipid peroxidation products and altered reduced glutathione level in livers. The altered enzyme activities in diabetes lead to changes in the tissue antioxidative defense system, disturbing the regulation of cell redox level.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/11798 must be provided.

1. Melatonin directly scavenges peroxyl and alkoxyl radicals and attenuates metabolic disorders due to diabetes in rats