Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

Abstract

Oxidative stress is an important mechanism of contrast-induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague-Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol-treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low-osmolar CM via an antioxidant effect.

Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

“…Vacuolization is often reversible even after extremely high dosages of RCM in rats [86, 106] and functional deterioration is absent or mild. In humans, both anuria without vacuolization and diffuse vacuolization without loss of renal functional have been described [107, 108].…”

Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury

“…Recently, studies have shown that renal ischemia, direct nephrotoxicity, and oxidative stress are responsible for the pathogenesis of CI-AKI [7, 8]. Our previous study showed that free radical scavengers, such as pentoxifylline, could effectively reduce reactive oxygen species (ROS), protecting the kidney from iodinated contrast-induced injury [9]. Additionally, scavenging reactive oxygen species (ROS) by recombinant manganese superoxide dismutase prevented reduction of eGFR and renal histologic damage that follow the administration of contrast media [10].…”

Treatment of COVID ‐19 with pentoxifylline: Could it be a potential adjuvant therapy?

“…Pentoxifylline constitutes a beneficial medication for ARDS and respiratory failure 12,13 . Research suggests the efficacy of pentoxifylline in improving end organ damage involving the heart, 14 the kidney, 15 the liver 16 and the brain 17 . Pentoxifylline helps more effectively control sepsis and lower its mortality in adults and neonates 18,19 …”