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.