Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

Abstract

The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/ kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and α-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

Synthesis, characterization and biological analysis of the complex [VO(Hdhp)2] (H2dhp = 2,3-dihydroxypyridine)

“…Regarding the proteinuria results, it is not clear whether the benefits of treatment with the new complex come from its acting directly on kidney function or indirectly, by countering the diabetic state and thus reducing food intake, glycosuria and urinary urea. Hence, a follow-up study could involve the induction of nephrotoxicity in rats by means of drugs such as gentamycin and indometacin, followed by administration of [VO(Hdhp) 2 ] and evaluation of proteinuria [41]. Early work suggested that the vanadate ion was the prevailing form of vanadium in the plasma.…”

The Effect of Breadfruit Leaves Infusion on Acute Renal Failure Rat model Abstract

“…Negative control group (I) were only fed and given water for 14 days, positive (II) and treatment groups (III, IV, and V) were induced by gentamycin and piroxicam for 7 days to promote inflammatory response so that the rats on each group experienced renal failure. 6 After induction, the treatment groups were given breadfruit leaves infusion by per oral and with different doses of 4.25%, 9.5%, and 19% for 7 days. After the treatments were done, the rats were fasted for 24 hours and each group were entered to a heater to dilate their veins for 5 minutes, after their tails were cut off and the blood taken into a tube and labeled for plasma creatinine measurement.…”

“…4,5 Drugs used in this study which are gentamycin and piroxicam are proven to be able to damage the kidneys for 7 days to cause renal failure. 6 Breadfruit leaves have antioxidant effects and are believed to be able to lessen renal damage because of its flavonoid contents that can decrease the creatinine levels in blood by inhibiting the activity of free radicals and lessening the damages. 7 According to assumption that breadfruit leaves contain flavonoid compounds which are anti-oxidants.…”

La investigación básica aplicada a la clínica en la lesión renal aguda

“…A piora de la función renal se observó cuando la gentamicina fue asociada a un antiinflamatorio no hormonal, la indometacina. Inversamente, no se observó potencial nefrotóxico en el tratamiento gentamicina cuando asociada a rofecoxibe, un AINH selectivo de COX-2, actualmente no disponible para uso clínico (15) .…”