Ketorolac- and warfarin-induced renal toxicity: ultrastructural and biochemical study

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drug classes worldwide. Although, these drugs have a potent analgesic and anti-inflammatory effects associated with nephrotoxicity. Factors such as advanced age and comorbidities may contribute to increase the risk of NSAID-related nephrotoxicity. The current study was designed to study the dual effect of non-NSAIDs and anticoagulants on the rat kidney. Methods: Thirty-two adult male albino rats were divided into four groups (n = 8): first, served as the control group which was orally administered with distilled water; second, served as the ketorolac (KT) group which received a daily intramuscular injection of ketorolac tromethamine (3 mg/kg/day); third, served as the warfarin (WR) group which was orally administered with racemic warfarin (0.3 mg/kg/day); and fourth, served as the combined (KT/WR) group which received an oral administration of WR (0.3 mg/kg/day) followed by an intramuscular injection of KT (3 mg/kg/day). After six consecutive days of daily treatment, all animals were sacrificed and their blood and tissue samples were collected.Results: A significant decrease in serum level of creatinine was observed in WR-and KT/WR-treated groups. However, urea increased significantly in the serum of the combined group, KT/WR. Furthermore, both WRand KT/WR-treated groups showed a significant increase in malondialdyhed (MDA) level; however, WR treatment induced a significant decrease in reduced glutathione (GSH) level. The total antioxidant capacity (TAC) of rat kidney showed a significant decrease in all treated groups. Electron microscopic investigations of kidney cortex localized variable degrees of focal degeneration, vacuolation, and vascular congestion in KTand WR-treated groups that are more vigorously attacking the cortical tissues in KT/WR-treated rats. Conclusions: We can conclude that the combined therapy of anti-inflammatory and anticoagulant drugs must be avoided or at least minimized, particularly in the elderly people, who mostly had other complications, in order to avoid the severe side effects on kidney structure and function.