Nitric oxide synthase inhibitors partially inhibit oxidative stress development in the rat brain during sepsis provoked by cecal ligation and puncture.
IOxidative stress development in different brain structures and the influence of nitric oxide (NO) overproduction during sepsis was investigated using male Wistar rats. Rats were subjected to cecal ligation and puncture (CLP) or were sham-operated. To evaluate the source of NO production, 30 min before the operation septic and control animals were treated with single intraperitoneal doses of NO synthase (NOS) inhibitors: L-NAME and aminoguanidine (AG) (10, 30 or 90 mg/kg) and 7-nitroindazole (7-NI) (30 mg/kg). The concentration of GSH in the cortex, brain stem, cerebellum, striatum and hippocampus significantly decreased post CLP at both early and late stage sepsis. Lipid peroxidation also occurred in the cortex and cerebellum in late stage sepsis. Pre-treatment with a non-selective NOS inhibitor (L-NAME) and with selective inducible and neuronal NOS inhibitors (AG and 7-NI) revealed benefit effects on the GSH concentrations. Unexpectedly, NOS inhibition resulted in diverse effects on TBARS concentrations, suggesting the importance of specific quantities of NO in specific brain structures during sepsis.
Ninković
Milica B
MB
Laboratory of Clinical Physiology, Instititute of Medical Research, Military Medical Academy, Crnotravska 17, 11002 Belgrade, Serbia. ninkomj@ptt.yu
Malicević
Zivorad M
ZM
Jelenković
Ankica
A
Dukić
Mirjana M
MM
Jovanović
Marina D
MD
Stevanović
Ivana D
ID
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002432:Cecum / Q000601:surgery*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects*; D011677:Punctures / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase