Palosuran in Gentamicin-Induced Acute Kidney Injury in an Experimental Rat Model

Abstract

Objective: Urotensin-II is a potent vasoconstrictor peptide and has fibrotic effects in the heart and kidneys and palosuran is a selective urotensin-II receptor antagonist. This study aimed to investigate the effects of palosuran, which has antifibrotic effects, in an acute kidney injury model formed with gentamicin and to reveal new treatment options for acute kidney injury cases. Methods: A total of 24 Wistar albino rats were randomly divided into 3 groups of 8 animals as the control group, the gentamicin group, and the gentamicin+palosuran group. The rats in the control group received a 1 × 1 mL intramuscular injection of saline for 8 days. To create acute kidney injury in the rats in the gentamicin group, an intramuscular injection of 100 mg/kg/day gentamycine was applied for 8 days. In the gentamicin + palosuran group, an intramuscular injection of 100 mg/kg/day gentamycine was applied for 8 days, together with 300 mg/kg palosuran dissolved in distilled water and administered by oral gavage twice a day for the same period. Serum urea, creatinine, calcium, albumin, total protein levels, and urine gamma-glutamyl transferase and protein levels were evaluated for all the groups. In addition, tubular degeneration, tubular necrosis, tubular regeneration, tubulointerstitial nephritis, microcalcification, and total histological scores of these groups were also examined histopathologically. Results: The urine gamma-glutamyl transferase levels of the gentamicin and gentamicin + palosuran groups were significantly higher than those of the control group (311 ± 60.5 and 140 ± 39.5 vs. 0.33 ± 0.22, P < .05). On the eighth day, the gamma-glutamyl transferase levels of the gentamicin + palosuran group were significantly lower than the gentamicin group (311 ± 60.5 vs. 140 ± 39.5, P < .05). A significant decrease was obtained in tubular necrosis in the gentamicin + palosuran group compared to the gentamicin group (2.5 ± 0.3 vs. 1.3 ± 0.4, P < .05). A statistically significant decrease was determined in the total histological score in the gentamicin + palosuran group compared to the gentamicin group (6.4 ± 0.7 vs. 4.7 ± 0.7, P < .05). Our results showed that the urotensin-II receptor antagonist, palosuran, had positive effects on tubular necrosis, tubular degeneration, tubular regeneration, and the total histological score in an experimental acute kidney injury model formed with gentamicin. Conclusion: The study results suggest that urotensin-II may play a role in the physiopathology of acute renal failure associated with gentamicin. These results are promising for the use of palosuran in the treatment of acute kidney injury.