Attenuation of renal ischemia/reperfusion injury by a triple drug combination therapy.
BACKGROUND
Renal ischemia is of great clinical interest because of its role in renal failure and renal graft rejection. The purpose of this study was to investigate the therapeutic effects of a combination therapy of: n-acetyl cysteine (NAC), a potent antioxidant, sodium nitroprusside (SNP), a nitric oxide donor and phosphormidon (P), an endothelin-1 converting enzyme inhibitor, on tissue protection against renal ischemia/reperfusion injury in the canine model.


METHODS
In this study, 15-20 kg male dogs were subjected to 90 minutes of warm unilateral renal ischemia after removal of one kidney and then divided into control, ischemia alone and treatment groups. Blood samples were collected from these dogs for measurement of kidney function tests and the kidneys were harvested at different time intervals for morphological evaluation, immunostaining and Tunnel Assay.


RESULTS
Kidney function tests (serum creatinine and blood urea nitrogen [BUN]) showed a significant difference between untreated and treated groups. ** P <0.01, * P< 0.0001 for treated versus untreated. The protective effect of the combination therapy is also supported by light microscopic studies, immunostaining of renal tissue sections for pro-inflammatory cytokines (TNF-alpha and IFN-gamma), iNOS, and apoptosis by TUNEL assay.


CONCLUSIONS
Our results suggest that pre-administration of a combination of NAC, SNP, and P attenuates renal ischemia/reperfusion injury. This has potential application in preservation of donor kidney for transplantation by protecting cells against free radical damage.
Sekhon
Charanpal S
CS
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.
Sekhon
Bipanjeet K
BK
Singh
Inderjit
I
Orak
John K
JK
Singh
Avtar K
AK
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D006020:Glycopeptides / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000473:pathology / Q000628:therapy*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control*; D012680:Sensitivity and Specificity
D006020:Glycopeptides; D009599:Nitroprusside; C008890:phosphoramidon; D000111:Acetylcysteine