[Hypoclorous acid modifies rat liver and heart enzymes of the pentose phosphate pathway and antioxidative defence 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. The aim of the present study was to investigate the mechanisms of hypochlorous acid-induced modification of antioxidant enzymes, which defence the cell under oxidative stress, and enzymes of the pentose phosphate pathway, which supply reducing equivalents in the cell. HOCl (100-1000 microM) in vitro inhibited considerably in a dose-dependent manner the activity of the enzymes of the pentose phosphate pathway in the rat liver postmitochondrial fraction. HOCI 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 postmitochondrial fraction HOCl (100-1000 microM) 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-glutathione 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.
Lapshina
E A
EA
Sudnikovich
E Iu
EIu
Kubyshin
V L
VL
Zabrodskaia
S V
SV
Maksimchik
Iu Z
IuZ
Zavodnik
I B
IB
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013367:Submitochondrial Particles / Q000201:enzymology
D000975:Antioxidants; D016877:Oxidants; D006997:Hypochlorous Acid; D010088:Oxidoreductases