ABSTRACT
BACKGROUND: In recent years, several lines of evidence have implicated reactive species as contributors to renal ischemia/reperfusion injury (I/R). This study was designed to investigate the effect of Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a broad-spectrum reactive species scavenger, in the prevention of renal I/R injury. METHODS: Experiments were performed on rats anesthetized with pentobarbital. After tracheotomy, the right femoral artery was cannulated and the mean arterial pressure and heart rate were recorded. A midline laparatomy was performed, and the renal arteries were carefully separated from surrounding tissues. After surgery and a stabilization period (60 min), the animals were randomly assigned to four groups: sham-operated; sham+MnTBAP; I/R; I/R+MnTBAP. In I/R groups, the rats were subjected to bilateral renal artery occlusion for 40 min followed by 6 h reperfusion. Other groups underwent the surgery protocol but did not undergo renal artery occlusion, and were maintained under anesthesia for the duration of the experiment. Rats were administered either MnTBAP (10 mg kg(-1), i.v. bolus, 15 min prior to I/R) or saline. Renal function was assessed by plasma creatinine (Cr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) measurements. The fractional excretion of Na(+) (FE(Na+)) and urinary N-acetyl-beta-D-glucosaminidase (NAG) activities were also measured. Renal section damage was evaluated by light microscopy, and oxidative stress status was evaluated by measurements of plasma and renal vitamin E levels. RESULTS: We found that MnTBAP significantly reduced the I/R-mediated increases in plasma Cr, BUN, AST, FE(Na+), and NAG and improved the renal tissue histology. CONCLUSION: Our results showed that MnTBAP was effective in preventing the development of I/R-induced renal injury.
Subject(s)
Free Radical Scavengers/therapeutic use , Metalloporphyrins/therapeutic use , Renal Artery Obstruction/drug therapy , Reperfusion Injury/drug therapy , Acetylglucosaminidase/urine , Animals , Aspartate Aminotransferases/blood , Blood Urea Nitrogen , Creatinine/blood , Kidney/pathology , Male , Rats , Rats, Sprague-Dawley , Reactive Nitrogen Species/antagonists & inhibitors , Reactive Oxygen Species/antagonists & inhibitors , Sodium/urine , Vitamin E/metabolismABSTRACT
Despite decades of study, the exact mechanism of action of lead, a potent neurotoxic agent, have not been fully elucidated. One of the suggested mechanism of lead neurotoxicity is apoptotic cell death. The present study sought to examine the effect of acute lead poisoning on apoptosis in rat hippocampus. Two to four and 12-14 week old rats were treated for 7 days with 15 mg/kg daily dose of lead acetate intraperitoneally. Control animals received distilled water. In treated groups, the blood lead levels was increased by about 17-19-folds. Histological study of hippocampus revealed apoptotic cells, using light and electron microscopy. In Western blot analysis, the ratio of Bax/Bcl-2 protein expression in hippocampus was significantly increased compared to controls. In conclusion, the lead induced cell death in hippocampus in vivo may partly be due to apoptosis.
