Background:
Reactive oxygen species (ros) have been shown to be involved in the reduction of glomerular filtration rate observed after gentamicin (genta) treatment in vivo, a phenomenon directly related with mesangial cell (mc) contraction. our previous study reported that genta induces concentration-dependent mc contraction and proliferation in vitro.
Methods:
To study the possible mediation of ros in the effect of genta, ros production was measured in primary cultures of rat mc stimulated with genta (10-5 mol/l). in addition, the mc response to genta in the presence of the ros scavengers superoxide dismutase (sod) and catalase (cat) was studied. mc activation and o2- production were studied in the presence of an inhibitor of the nadp(h) oxidase, diphenylene iodinium (dpi), and in the presence of l-name, an inhibitor of nitric oxide synthases (nos). finally, the effects of genta on sod activity and mrna expression were examined.
Results:
Genta (10-5 mol/l) induced an increase in o2- production and sod activity that was neither accompanied by an elevation in cytosolic cu/zn-sod mrna expression nor by h2o2 accumulation. genta induced mc contraction and proliferation that were inhibited by sod plus cat. both the extracellular and intracellular ros donor systems, xantine+xantine oxidase (x+xo) and dimethoxinaphtoquinone (dmnq), respectively, also stimulated mc contraction and proliferation. genta-induced mc activation and o2- production were inhibited by dpi. genta-induced o2- production was inhibited by l-name. furthermore, genta did not induce detectable changes in membrane fluidity and lipid peroxidation.
Conclusions:
These results strongly suggest that an oxidative-mediated pathway exists in genta-induced mc activation. a portion of the production of o2- may be due to nadp(h) oxidase and nos activation. the amount of ros produced, rather than having a toxic effect, might play a role as a mediator of genta-induced mc activation