Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

Area of Science:

• Nephrology
• Pharmacology
• Toxicology

Background:

• Frequent use of nonsteroidal anti-inflammatory drugs (NSAID) alongside gentamicin increases the risk of nephrotoxic renal failure.
• Cyclooxygenase-1 (COX-1) synthesizes renal prostaglandins, while Cyclooxygenase-2 (COX-2) is involved in inflammation; both are inhibited by non-selective NSAID.
• Selective COX-2 inhibitors may offer a safer alternative with fewer renal side effects compared to non-selective NSAID.

Purpose of the Study:

• To investigate whether the combination of rofecoxib (a selective COX-2 inhibitor) and gentamicin can prevent gentamicin-induced renal injury.
• To compare the renal effects of gentamicin combined with rofecoxib versus gentamicin combined with indomethacin (a non-selective NSAID).

Main Methods:

• Male Wistar rats were administered gentamicin alone, indomethacin alone, rofecoxib alone, gentamicin + rofecoxib, or gentamicin + indomethacin for 5 days.
• Renal function was assessed using creatinine clearance.
• Alpha-glutathione-S-transferase concentrations were measured as a marker of renal injury.

Main Results:

• The combination of gentamicin and indomethacin significantly worsened renal function (creatinine clearance: 0.199 +/- 0.019 ml/min).
• The combination of gentamicin and rofecoxib did not exhibit a nephrotoxic effect, with creatinine clearance remaining at 0.242 +/- 0.011 ml/min.
• Rofecoxib co-administration with gentamicin showed no adverse impact on renal function markers.

Conclusions:

• Selective COX-2 inhibitors, such as rofecoxib, can be a viable alternative to conventional NSAID in patients at risk of nephrotoxicity.
• Combining gentamicin with a selective COX-2 inhibitor appears to mitigate the nephrotoxic effects associated with gentamicin and non-selective NSAID.