Gentamicin is an
aminoglycoside antibiotic that is very effective in treating different gram negative
infections, however, one of its main side effects is nephrotoxicity.
Gentamicin-induced decreases in glomerular filtration rate could be mediated by mesangial cell contraction.
Resveratrol, a natural hydroxystilbene, has been identified to be a potent
antioxidant with many
biological activities including protection against
kidney diseases. As we have previously demonstrated that
gentamicin induced a reduction of planar surface area of cultured rat mesangial cells, and that
resveratrol has a protective effect on
gentamicin-induced nephrotoxicity in vivo, the aim of this study was to investigate the effect of
resveratrol on
gentamicin-induced mesangial cell contraction. This study demonstrates that the contractile effect of
gentamicin on mesangial cells can be prevented by incubation with
resveratrol at an optimal dose of 10 microM, as it blunted the
gentamicin-induced reduction in planar cell surface area and the number of contracted cells. Besides, the preincubation with 10(-5)M diphenylene iodinium (DPI), an inhibitor of the
NADP(H)
oxidase, also blunted
gentamicin-induced cell contraction. This preventive effect was higher when cells were incubated with both substances together. These results strongly suggest that the protective effect
resveratrol against
gentamicin-induced reduction in renal function in vivo could be mediated by inhibiting
gentamicin-induced mesangial cells contraction.