Effects of efonidipine hydrochloride (NZ-105), a new calcium antagonist, against acute renal failure in rats.
1. We investigated the effect of efonidipine hydrochloride (NZ-105) against acute renal failure (ARF) in male Wistar rats. ARF was produced by ischemia or glycerol. 2. Ischemia-induced ARF was produced by right nephrectomy and clamping of the left renal artery for 60 min, followed by reperfusion. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. The plasma creatinine and urea nitrogen concentrations were markedly elevated in the ischemia ARF group on the 1st day, but the elevation was significantly suppressed by NZ-105 treatment. 3. Glycerol-induced ARF was produced by intramuscular injection of 50% (v/v) glycerol (10 ml/kg) in rats which were restricted to drinking water for 24 hr. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. NZ-105 significantly attenuated the severe impairment of creatinine and urea nitrogen clearances and the elevated fractional sodium excretion (FENa) caused by ARF. 4. In the kidney homogenate, NZ-105 (10(-6)-10(-4) M) inhibited lipid peroxidation induced by ascorbic acid and Fe or by NADPH and the inhibitory effect of NZ-105 was stronger than alpha-tocopherol, an antioxidant agent. NZ-105 (10(-5)-10(-3) M) showed radical scavenging action against diphenyl-p-picrylhydrazyl and galvinoxyl induced radicals. 5. These findings suggest that NZ-105 prevents the renal damage caused by the two kinds of ARF. Moreover, the inhibitory effects of NZ-105 against lipid peroxidation and radical formation may be one of the mechanisms involved in the prevention of ARF.
Shudo
C
C
Shiraoka Research Station of Biological Science, Nissan Chemical Industries Ltd., Japan.
Masuda
Y
Y
Sugita
H
H
Tanaka
S
S
Tomita
K
K
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005990:Glycerol / Q000633:toxicity; D007511:Ischemia / Q000150:complications; D007668:Kidney / Q000098:blood supply; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D016166:Free Radical Scavengers; D005609:Free Radicals; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D005990:Glycerol