Gentamicin treatment induces simultaneous mesangial proliferation and apoptosis in rats.
BACKGROUND
Gentamicin (G)-induced acute renal failure is characterized by an impairment of glomerular function without apparent changes in glomerular structure. However, G stimulates reactive oxygen species (ROS)-mediated mesangial cell proliferation in vitro. We studied whether G promotes mesangial cell apoptosis in vitro, and if apoptosis and proliferation in parallel may occur in glomerular cells in vivo after a renal damage induced by G treatment.


METHODS
For in vivo studies, rats were treated with G (100 mg/kg body weight/day) for 6 days, and functional and histologic studies were performed. For in vitro studies, mesangial cell proliferation and apoptosis were evaluated after 24, 48, and 72 hours of 10(-5) mol/L G incubation.


RESULTS
After G injections, the number of nuclei per glomerulus did not change, whereas proliferating and apoptotic cell numbers increased. G increases DNA synthesis and cell number in cultured mesangial cells, and increases markedly the apoptotic cell number. ROS scavengers superoxide dismutase and catalase reduce G-induced mesangial cell apoptosis, whereas the incubation with the ROS donor system xanthine plus xanthine oxidase increases apoptosis to levels similar to G. G-induced cellular proliferation and apoptosis either in vitro or in vivo is associated to an early increase in the pro-apoptotic protein Bax and a delayed increase in the survival protein Bcl-2.


CONCLUSIONS
G simultaneously induces proliferation and apoptosis of mesangial cells in vitro and glomerular mesangial cells in vivo. ROS may mediate G-induced mesangial apoptosis in vitro. The equilibrium proliferation/apoptosis may maintain mesangial cell number within normal limits after a G-induced glomerular insult.
Martínez-Salgado
Carlos
C
Departamento de Fisiología y Farmacología, Instituto Reina Sofía de Investigación Nefrológica, Universidad de Salamanca, Salamanca, Spain.
Eleno
Nélida
N
Morales
Ana I
AI
Pérez-Barriocanal
Fernando
F
Arévalo
Miguel
M
López-Novoa
José M
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005839:Gentamicins / Q000633:toxicity*; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D005839:Gentamicins; D017382:Reactive Oxygen Species