The Hepatoprotective Effect of Nitric Oxide Modulators and Antioxidants in Hepatic Ischemia/Reperfusion Injury in Albino Rats | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 21, Volume 28, Issue 1, June 2008, Page 307-324 PDF (199.79 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2008.36990 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
| Salah El Deen Elsayed* 1; Amr Fouad2 | ||||
| 1Physiology Dept. Faculty of Medicine, El-Minia University | ||||
| 2Pharmacology Dept. Faculty of Medicine, El-Minia University | ||||
| Abstract | ||||
| Warm ischemia/reperfusion injury (IRI) of the liver is a major determinant of the outcome of a variety of clinical conditions. During the ischemic phase, tissue injury occurs due to oxygen deficiency. However, much injury arises with the restitution of the circulation (reperfusion injury), in which the generation of reactive oxygen species (ROS) plays a fundamental role. Several studies have emphasized the positive effect of antioxidants in attenuating IRI in many tissues. The role of nitric oxide and its action as an oxidant/antioxidant is considered. The aim of the present work was to investigate the potential of NO in modulating warm IRI of the liver and its possible interaction with different antioxidants in a trial to minimize that injury. Seventy two albino rats were used in the present study. Rats were classified into the following groups (8 rats each): The 1st group of rats was subjected to 30min of ischemia followed by 60min of reperfusion. The 2nd group was Sham-operated rats underwent the same surgical procedure without interruption of the blood flow to the liver and served as controls. 3rd group L-nitro-arginine methyl ester (L-NAME) treated group, 50mg/k g (Sigma), the 4th, 5th, and 6th groups were the NO-donor, L-Arginine (Sigma) treated groups, in 3 different doses (100, 300, 500mg/k g). The drugs were administered intravenously 5min before ischemia-induction. The 7th group allopurinol (Sigma) treated group (50mg/k g), the 8th group desferrioxamine treated group (desferal) (Sigma) 100mg/k g and the 9th group vitamin C treated group (Sigma) 100mg/k g. Allopurinol was administered intraperitoneally 10min before the induction of ischemia, whereas desferal and vitamin C were administered intravenously 5min before the induction of ischemia. The left lobe of the liver of albino rats was subjected to 30 min warm ischemia followed by 60 min of reperfusion. Serum liver enzymes (AST, ALT, and LDH) were determined as a measure of tissue injury. Plasma nitrite level was assessed as a measure of nitric oxide production. Hepatic levels of malondialdehyde were quantified to evaluate the oxidative stress, while those of superoxide dismutase, catalase, and glutathione served as a determinant of the antioxidant status. Thirty minutes of warm ischemia followed by reperfusion for 60 min inflicted signs of tissue injury accompanied by oxidative stress and exhaustion of tissue antioxidants and plasma nitrite level. This was exacerbated with the nitric oxide block er L-NAME. On the other hand, the nitric oxide donor (L-arginine) its lowest and intermediate doses (100, 300mg/k g) could attenuate that injury; while in its highest dose (500mg/k g) accentuated the injury. Treatment with the xanthine oxidase inhibitor (allopurinol) was accompanied with a mild protective effect. Treatment with the iron-chelating agent (desferrioxamine) was accompanied with a substantial protective effect, while the treatment with vitamin C caused a moderate protection. The results clearly demonstrated that nitric oxide supply during IRI is up to a certain limit beneficial in ameliorating hepatic IRI, while its paucity was accompanied with accentuation of the injury. It seems that too high or too low level of NO is detrimental and aggravates IRI and its fine-tuning is a prerequisite to protect at least hepatic tissue. Furthermore, the results revealed that the antioxidant allopurinol did not practically improve the deteriorated livers subjected to IRI. Also, the results proved that iron-chelator (desferrioxamine) exhibited a very strong protective effect. The role of vitamin C warrants further elucidation, as its sole administration could confer protection to the liver against IRI. | ||||
|
Statistics Article View: 92 PDF Download: 69 |
||||
