Objective: To determine the protective effects of the leukotriene inhibitors MK-886 and Zileuton on doxorubicin (DX)-induced acute kidney damage in a rat model.
Methods: A rat model of acute kidney injury (AKI) was established by a 3-day regimen of DX. The animals were suitably treated with MK-866 or Zileuton, and untreated DX injected and healthy controls were also included. The rat sera were analyzed for the levels of creatinine and urea as markers of renal injury and for the levels of the oxidative stress markers GSH and MDA using standard assays. In addition, the renal tissues of the rats were processed and histo-pathologically analyzed by HE staining.
Results: DX injection significantly increased the levels of creatinine and urea, indicating dysfunctional kidneys. The levels of both metabolites were restored to baseline levels by MK-866 while Zileuton significantly affected only urea levels. In addition, the GSH levels were significantly decreased and that of MDA was increased upon DX exposure, indicating oxidative damage. While MK-866 treatment significantly reversed the status of both GSH and MDA compared to the DX group, Zileuton had no significant effects on the levels of either. Finally, DX caused extensive renal tissue damage, which was rescued by MK-866 and to a lesser extent by Zileuton.
Leukotriene inhibitors MK-886; Zileuton; Doxorubicin (DX)-induced acute kidney damage; Dysfunctional kidneys; Creatinine; Urea; Acute renal failure
Acute kidney injury (AKI) is characterized by a sudden (about several hours to several days) decline in renal tissue function . Several studies have shown that AKI often progresses to chronic kidney disease (CKD), resulting in high mortality and morbidity . Despite treatment options, development of acute renal failure (ARF) is associated with increased mortality rates from 40% to 90%, as well as non-renal complications . The increasing prevalence of AKI has been reported in both developing and developed countries and is consistently associated with increased mortality and morbidity, as well as increased incidence of CKD . Every year, 2 million people die of AKI worldwide .