title: Beneficial effect of pentoxifylline on cisplatin-induced acute renal failure in rabbits.
abstract: Pentoxifylline (PTX) has been reported to inhibit TNF-alpha production and prevent several types of acute renal failure. This study was undertaken to determine the effect of PTX on the cisplatin-induced acute renal failure in rabbits. Rabbits received a single injection of cisplatin (5 mg/kg, i.p.) with or without PTX pretreatment (30 mg/kg, i.v.). Alterations in renal function, apoptotic cell death, and TNF-alpha mRNA expression were measured at 24 or 48 h after cisplatin injection. Cisplatin caused an increase in BUN and serum creatinine levels, a reduction in GFR, and an increase in fractional Na+ excretion. Such changes were significantly attenuated by PTX pretreatment (30 mg/kg, i.p.) 30 min before and 24 h after cisplatin injection. Morphological evaluation showed that cisplatin injection induced diffuse proximal tubular necrosis and the effect was reduced by PTX pretreatment. Cisplatin induced apoptotic cell death in renal cortex and the effect was significantly prevented by PTX. Treatment of opossum kidney cells with cisplatin resulted in cell death, which was significantly prevented by PTX. The increase in lipid peroxidation and the decrease in renal blood flow induced by cisplatin were not affected by PTX. The expression of TNF-alpha mRNA was increased after cisplatin injection and the effect was inhibited by PTX pretreatment. These results suggest that cisplatin-induced acute renal failure in rabbits is associated with an induction of TNF-alpha-mediated apoptosis, and that PTX may exert a protective effect against cisplatin nephrotoxicity by inhibiting TNF-alpha production.
authors.affiliation: Department of Physiology, College of Medicine, Pusan National University, Pusan, Korea. kim430@pusan.ac.kr
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Choi
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kwon
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Suk
authors.initials: JS
authors.lastname: Woo
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Jung
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002945:Cisplatin; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D010431:Pentoxifylline / Q000494:pharmacology*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin; D010431:Pentoxifylline