Effect of a novel NSAID derivative with antioxidant moiety on oxidative damage caused by liver and cerebral ischaemia-reperfusion in rats.
Tissue ischaemia-reperfusion evokes toxic and harmful biochemical processes such as oxidative stress and inflammation. The aim of this study is to investigate the indices of tissue damage in rat liver and brain after ischaemia-reperfusion injury of these organs, and to study prospective cytoprotection of molecules such as the novel anti-inflammatory N-(2-thiolethyl)-2-(2-[N'-(2,6-dichlorophenyl)amino] phenyl)acetamide (compound 1) and alpha-tocopherol. Two experimental models were studied: firstly, 30 min liver ischaemia via hepatoduodenal ligament clamping followed by 60 min reperfusion; and secondly, 45 min cerebral ischaemia via bilateral common carotid artery occlusion followed by 90 min reperfusion. Compound 1 and alpha-tocopherol were administered intraperitoneally before induction of ischaemia. We hereby report that compound 1, a molecule that combines potent in-vitro antioxidant and in-vivo anti-inflammatory activity with low gastrointestinal toxicity, offered protection in-vivo against liver or brain ischaemia-reperfusion-induced damage. Both compound 1 and alpha-tocopherol prevented changes in lipid peroxidation in the rat liver and brain tissue and in tumour necrosis factor (TNF-alpha) levels in brain. Also compound 1 attenuated glutathione depletion, evoked by ischaemia-reperfusion, in the rat brain but not in the liver. These results could be explained on the basis of the antioxidant/anti-inflammatory properties of compound 1 and suggest its beneficial effect and potential therapeutic use in post-ischaemic injury.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54006, Greece. angeliki@achibo.com
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Kourounakis
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Tsiakitzis
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Paramithiotis
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Kotzampassi
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Kourounakis
D000081:Acetamides / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D008099:Liver / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000662:veterinary; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000494:pharmacology*
D000081:Acetamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; C472071:N-(2-thiolethyl)-2-(2-(N'-(2,6-dichlorophenyl)amino) phenyl)acetamide; D024502:alpha-Tocopherol