Effects of trapidil on renal ischemia-reperfusion injury.

There is increasing evidence to suggest that reactive oxygen and nitrogen species play a role in the pathogenesis of renal ischemia-reperfusion (I/R) injury. This study was designed to determine the possible protective effects of trapidil treatment against oxidative and nitrosative tissue injury of kidney induced by I/R. A renal I/R injury was induced by a left renal pedicle occlusion by ischemia for 45 minutes, followed by 1 hour of reperfusion with contralateral nephrectomy in I/R and I/R + trapidil groups. Trapidil (8 mg/kg intravenously) was administrated immediately before reperfusion phase. At the end of the reperfusion period, rats were killed. Then, renal tissue samples were taken for biochemical analysis and histopathological evaluation, and blood samples were obtained to determinate serum urea, aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNF-alpha) levels. Ischemia-reperfusion injury caused significant increases in myeloperoxidase activity and malondialdehyde and 3-nitrotyrosine levels in renal tissue and elevated serum urea, AST, and TNF-alpha levels. In addition, severe deterioration of renal morphology was seen in the I/R group. Trapidil treatment significantly reduced in biochemical parameters, as well as serum urea, AST, and TNF-alpha levels. Furthermore, renal tissue injury was markedly attenuated with trapidil treatment. These data suggest that reactive oxygen species and reactive nitrogen species play a causal role in I/R-induced renal tissue, and trapidil has a renoprotective effect against oxidative and nitrosative kidney damage.

Protective effect of trapidil against oxidative organ damage in burn injury.

Animal models of thermal injury indicate reactive oxygen species and inflammatory cytokines as causative agents in tissue injury on various organs distant from the original wound. Trapidil has various properties, such as inhibition of platelet aggregation and lipid peroxidation as well as reduction of the inflammatory response to injury. This study was designed to determine the possible protective effect of trapidil treatment against oxidative organ damage in lung, intestine and kidney induced by cutaneous thermal injury. Thirty Wistar rats were randomly divided into five groups. Sham group (n=6) was exposed to 21 degrees C water while burn-3 h group (n=6) and burn+trap-3h group (n=6), burn-24 h (n=6) and burn+trap-24 h groups were exposed to boiling water for 12s to produce a full thickness burn in 35-40% of total body surface area. In both burn+trap-3 h and burn-trap-24 h group, 8 mg/kg trapidil was given intravenously immediately after thermal injury. Three and 24 h later, tissue samples were taken for biochemical analysis from lung, intestine and kidney and blood samples were obtained to determinate serum TNF-alpha levels. Cutaneous thermal injury caused a significant increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) and 3-nitrotyrozine (3-NT) levels in all tissues and elevated serum TNF-alpha levels at post-burn 3 and 24 h. Trapidil treatment significantly reduced in biochemical parameters, as well as serum TNF-alpha levels. These data suggest that trapidil has a protective effect against oxidative organ damage in burn injury.