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Resveratrol inhibits gentamicin-induced mesangial cell contraction
Ana I Morales1, Alicia Rodríguez-Barbero, Cesáreo Vicente-Sánchez
1Instituto "Reina Sofía" de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
Abstract:
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.
Insights
Resveratrol prevents gentamicin-induced kidney damage by inhibiting mesangial cell contraction. This natural antioxidant protects kidney function by reducing cell contraction caused by the antibiotic.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Gentamicin, an aminoglycoside antibiotic, effectively treats gram-negative infections but can cause nephrotoxicity.
- Mesangial cell contraction is a potential mechanism underlying gentamicin-induced decreases in glomerular filtration rate.
- Resveratrol, a natural antioxidant, shows protective effects against kidney diseases.
Purpose of the Study:
- To investigate the effect of resveratrol on gentamicin-induced mesangial cell contraction.
- To determine if resveratrol can prevent the reduction in mesangial cell planar surface area and cell contraction induced by gentamicin.
- To explore the role of NADP(H) oxidase in gentamicin-induced mesangial cell contraction.
Main Methods:
- Cultured rat mesangial cells were treated with gentamicin and/or resveratrol.
- Cellular responses, including planar surface area and the number of contracted cells, were measured.
- The effect of diphenylene iodinium (DPI), a NADP(H) oxidase inhibitor, was assessed.
Main Results:
- Resveratrol (10 microM) prevented gentamicin-induced mesangial cell contraction, reducing the decrease in planar cell surface area and the number of contracted cells.
- Diphenylene iodinium (DPI) also inhibited gentamicin-induced cell contraction.
- Combined incubation with resveratrol and DPI showed a higher preventive effect.
Conclusions:
- Resveratrol effectively prevents gentamicin-induced mesangial cell contraction.
- NADP(H) oxidase activity may mediate gentamicin-induced mesangial cell contraction.
- Resveratrol's protective effect against gentamicin nephrotoxicity in vivo may be mediated by inhibiting mesangial cell contraction.
