Effect of Pentoxifylline on Ischemic Acute Renal Failure in Rabbits

Abstract

Previous studies have demonstrated that levels of tumor necrosis factor-alpha (TNF-alpha) or its mRNA expression are increased in acute renal failure of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-alpha production, provides a protective effect against ischemic acute renal failure in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with PTX (30 mg/kg, i.v.) 10 min before release of clamp. At 24 h of reperfusion of blood after ischemia, changes in renal function, renal blood flow, and the expression of TNF-alpha mRNA were evaluated. Ischemia/reperfusion caused a marked reduction in GFR, which was accompanied by an increase of serum creatinine levels. Such changes were significantly attenuated by PTX pretreatment. PTX ameliorated the impairment of renal tubular function, but it had no effect on the reduction of renal blood flow induced by ischemia/reperfusion. The protective effect of PTX on functional changes was supported by morphological studies. The impairment of glucose and phosphate reabsorption in postischemic kidneys was associated with a depression in the expression of Na+-glucose and Na+-Pi transporters. The expression of TNF-alpha mRNA was increased after reperfusion, which was inhibited by PTX pretreatment. The PTX pretreatment in vitro prevented the release of lactate dehydrogenase induced by an oxidant t-butylhydroperoxide in rabbit renal cortical slices, but it did not produce any effect on the oxidant-induced lipid peroxidation, suggesting that PTX protection is not resulted from its antioxidant action. These results suggest that PTX may exert a protective effect against ischemic acute renal failure by inhibiting the production of TNF-alpha in rabbits.

Pretreatment with Pentoxifylline andN-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

“…These results suggest that PTX may exert a protective effect against ischemic acute renal failure by inhibiting the production of TNF-α in rabbits. 37 In conclusion, the significant increase in MDA levels, decrease in GSH, and destructive appearance in histology accompanied by partial impaired function in the kidney suggested that hepatic IR-induced renal injury may be mediated through oxidative reactions. In addition, PTX and NAC administrations protected kidney tissue against this oxidative damage caused by hepatic IR injury.…”

Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats

“…Even this delayed administration protected the animals from the development of brain damage as well as from the linear increase of urinary protein, which suggests that PTX may "cure or reverse" the kidney abnormalities reported in this animal model (Abumiya et al, 1996). Indeed, a nephroprotective effect of PTX in experimentally induced renal failure (Kim et al, 2001) and an antiproteinuric effect in patients with nephropathy (Ducloux et al, 2001) has been reported.…”

“…Studies of the anti-inflammatory effects of PTX in vivo have focused attention on tissue injury after ischemia. Thus, in vivo PTX treatment reduced ischemia-reperfusion injury in the lung (Thabut et al, 2001), intestine (Sener et al, 2001), liver (Iwamoto et al, 2002), kidney (Kim et al, 2001), spinal cord (Savas et al, 2002), and brain of different animal species including rats, mice, and dogs (Toung et al, 1994;Sirin et al, 1998;Eun et al, 2000). Inflammatory processes accompany tissue injury regardless of the organ system involved, and chronic inflammation may predispose to ischemia in peripheral organs and to brain damage (Lindsberg and Grau, 2003).…”

Effects of Pentoxifylline on Amikacin-Induced Nephrotoxicity in Rats

“…[12][13][14][15][16] In animal models, it has been shown that PTX also prevents progressive renal damage associated with septic shock, [17] likely by protecting the renal microcirculation. [12] It may also exert a protective effect on tubular function in patients with ischemic/ reperfusion injury, [18] as well as have a protective benefit in nephrotoxicity induced by cisplatin, [19] myoglobinuria, [20] and cyclosporine. [21] A prospective randomized blinded study [22] in critically ill patients undergoing continuous venovenous hemofiltration (CVVH) revealed that continuous i.v.…”