Beneficial effects of rutin and L-arginine coadministration in a rat model of liver ischemia-reperfusion injury.
Reperfusion following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) I/R, 3) I/R+rutin, 4) I/R+L-arginine, and 5) I/R+rutin+L-arginine. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and L-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated I/R rats compared with sham-operated animals, whereas treatment with rutin or L-arginine in I/R rats reduced hepatic damage. Interestingly, combined therapy with rutin and L-arginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or L-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH, RSH groups, and liver histopathology, which showed the highest protective effects following the coadministration of rutin and L-arginine. Finally, the combined therapy protocol resulted in a significant induction of liver HO-1 and a concomitant reduction of iNOS expression that may both be responsible for the beneficial effects of the proposed pharmacological protocol.
Acquaviva
Rosaria
R
Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, Viale Andrea Doria 6, 95123 Catania, Italy. racquavi@unict.it
Lanteri
Raffaele
R
Li Destri
Giovanni
G
Caltabiano
Rosario
R
Vanella
Luca
L
Lanzafame
Salvatore
S
Di Cataldo
Antonio
A
Li Volti
Giovanni
G
Di Giacomo
Claudia
C
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D013438:Sulfhydryl Compounds; D012431:Rutin; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase