Roles of hemodynamic and tubular factors in gentamicin-mediated nephropathy.
Gentamicin (GM) often causes polyuric acute renal failure (ARF) in humans and animals. GM-mediated ARF in rats was accompanied with activated renin-angiotensin system, increased renal endothelin content, and enhanced lipid peroxidation. Suppression of the renin-angiotensin activity by desoxycorticosterone acetate and saline drinking, and treatment with superoxide dismutase attenuated the GM-induced decline in whole-kidney GFR with well-maintained RBF but did not reduce the severity of tubular necrosis. On the other hand, treatment with dimethylthiourea, a hydroxyl radical scavenger, attenuated the GM-mediated decline in GFR and lessened tubular necrosis but did not ameliorate the reduction in RBF. These data suggest contributions of both vascular and tubular factors to the GM-induced decline in GFR in rats. However, relative importance of these factors probably differs with different doses of the agent.
Hishida
A
A
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Nakajima
T
T
Yamada
M
M
Kato
A
A
Honda
N
N
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D003900:Desoxycorticosterone / Q000627:therapeutic use; D005440:Fluid Therapy; D016166:Free Radical Scavengers; D005839:Gentamicins / Q000009:adverse effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use
D016166:Free Radical Scavengers; D005839:Gentamicins; D003900:Desoxycorticosterone; C038983:1,3-dimethylthiourea; D013482:Superoxide Dismutase; D013890:Thiourea