Abstract |
Renal ischemia is of clinical interest because of its role in renal failure and also renal graft rejection. To evaluate the effect of the combination of N-acetylcysteine (NAC), a potent antioxidant, sodium nitroprusside (SNP), a nitric oxide donor, and phosphoramidon (P), an endothelin converting enzyme inhibitor, on tissue protection against ischemia-reperfusion injury, we studied the biochemical and morphological changes due to 90 min of renal ischemia-reperfusion in the rat model. Ninety min of ischemia caused very severe injury and the animals could not survive after 4 days without any treatment. Whereas, animals in the treated groups survived i.e. the NAC group (25%), NAC + SNP group (43%) and in the NAC + SNP + P group (100%), 2 weeks after 90 min of ischemia. A significant increase in the serum levels of creatinine and urea nitrogen was shown in the untreated group and to a much lesser extent in the treated group, especially in the NAC + SNP + P group. The protective effect was also supported by light microscopic studies on renal tissue sections. We also measured the activities of antioxidant enzymes in tissue homogenates. With the exception of Mn-superoxide dismutase, the activities of antioxidant enzymes ( catalase, glutathione peroxidase, CuZn- superoxide dismutase) were decreased in the untreated kidney. The administration of NAC alone and NAC + SNP protected against the loss of activities. Treatment with a combination of NAC, SNP and P showed a synergistic effect as evidenced by the best protection. These results suggest that pre-administration of a combination of antioxidant (NAC) with endothelin derived vasodilators ( sodium nitroprusside and Phosphoramidon) attenuates renal ischemia-reperfusion injury, e.g. in donor kidney for transplantation, by protecting cells against free radical damage.
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Authors | Kazushige Dobashi, Inderjit Singh, John K Orak, Kohtaro Asayama, Avtar K Singh |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 240
Issue 1-2
Pg. 9-17
(Nov 2002)
ISSN: 0300-8177 [Print] Netherlands |
PMID | 12487367
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antioxidants
- Glycopeptides
- Nitroprusside
- Catalase
- Glutathione Peroxidase
- Superoxide Dismutase
- phosphoramidon
- Acetylcysteine
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Topics |
- Acetylcysteine
(pharmacology)
- Animals
- Antioxidants
- Catalase
(metabolism)
- Disease Models, Animal
- Drug Therapy, Combination
- Glutathione Peroxidase
(metabolism)
- Glycopeptides
(pharmacology)
- Ischemic Preconditioning
- Kidney
(drug effects, enzymology, pathology)
- Male
- Nitroprusside
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(pathology, prevention & control)
- Superoxide Dismutase
(metabolism)
- Time Factors
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