Oxidative stress in the rats brain capillaries in sepsis--the influence of 7-nitroindazole.
As a part of blood-brain barrier, brain capillaries participate in pathophysiological events during systemic inflammation. We investigated the effects of 7-nitroindazole (7-NI), selective neuronal nitric oxide synthase (NOS) inhibitor, to oxidative status (OS) of brain capillaries. Adult Wistar rats were randomized at groups: control group (CG) (sham operated), sepsis group (GS) (cecal ligation and perforation with inoculation of Escherichia coli (ATCC 25922), 7-NI group (G7-NI), (30 mg/kg b/w i.p.) and 7-NI + sepsis group (G7-NIS), (7-NI was applied 30 minutes before operation). Lipid peroxidation index (LPI), nitrite concentration, superoxide dismutase (SOD) activity and superoxide anion (O2*-) content were determined 3, 6, 24 and 48 hour in each group. Cerebral capillaries were separated from non-vascular brain tissue using sucrose gradient. Compared to controls, LPI, nitrite and O2*- increased at SG. In the G7-NIS, LPI reached control values at the 24th and 48th hour, while nitrite were decreased at the 3rd and 24th hour, compared to controls. In the same group, O2*- decreased at the 3rd, 6th and 24th hour, although SOD showed variable activity. The systematic nNOS inhibition with 7-NI forces OS on early terms of sepsis, but lately it contributes to the normalization of OS in cerebral capillaries.
Ninković
M
M
Institute of Medical Research, Military Medical Academy, Crnotvarska 17, 11002 Belgrade, Serbia vmaimi@Eunet.yu
Malicević
I
I
Jelenković
A
A
Jovanović
D M
DM
Dukić
M
M
Vasiljević
I
I
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000187:drug effects*; D002429:Cecal Diseases / Q000150:complications; D002432:Cecum; D004927:Escherichia coli Infections / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology*; D007416:Intestinal Perforation / Q000150:complications; D008026:Ligation; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D007191:Indazoles; D009573:Nitrites; D013481:Superoxides; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; C080122:7-nitroindazole