2-o-octadecylascorbic-acid and Body-Weight

To elucidate the role of peripheral dopamine D1 receptors in cisplatin-induced acute renal injury, effect of zelandopam (YM435, (-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a selective renal dopamine D1 receptor agonist, on cisplatin-induced acute renal failure in rats was studied. Rats were divided into six groups: control, cisplatin and cisplatin plus zelandopam (30, 100, 300 mg/kg p.o. twice, 75 and 15 min before cisplatin injection) or the free radical scavenger CV-3611 (2-O-octadecylascorbic acid, 10 mg/kg p.o., 75 min before cisplatin injection) treated groups. Rats received intraperitoneal injection of cisplatin at a dose of 5 mg/kg. Four days after cisplatin injection, plasma creatinine, blood urea nitrogen and body weight were measured and the kidneys were removed for histological examination. Cisplatin induced acute renal failure characterized by the increases in plasma creatinine and blood urea nitrogen with tubular damage, and decreased body weight. Zelandopam dose-dependently prevented all these changes. The free radical scavenger CV-3611 significantly attenuated a decrease in body weight and renal dysfunction without reducing tubular damage. The present study is the first demonstration for that a selective dopamine D1 receptor agonist is effective in preventing acute renal failure induced by cisplatin.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Blood Urea Nitrogen; Body Weight; Cisplatin; Creatinine; Dose-Response Relationship, Drug; Epithelial Cells; Isoquinolines; Kidney Tubules; Male; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Tetrahydroisoquinolines

We examined the modifying effect of hemicalcium ascorbate (Ca-Asc), and its lipophilic derivatives, 2-O-octadecylascorbic acid (CV-3611) and ascorbyl palmitate (AscP), on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in ODS rats (a mutant unable to synthesize ascorbic acid). Male 14-week-old ODS rats were given a modified AIN-A diet or the diet containing 0.06% 3'-Me-DAB, and drinking water containing 0.1% ascorbic acid. Rats were divided into the following eight groups: Group 1, no treatment (basal diet alone); Group 2, Ca-Asc; Group 3, CV-3611; Group 4, AscP;Group 5, 3'-Me-DAB; Group 6, 3'-Me-DAB + Ca-Asc; Group 7, 3'-Me-DAB + CV-3611; and Group 8, 3'-Me-DAB + AscP. Ca-Asc (2 g/kg), CV-3611 (0.2 g/kg), and AscP (0.6 g/kg) was administered once every day by gavage. 3'-Me-DAB was given in the basal diet. After 17 weeks, animals were killed by exsanguination, and the liver was weighed and processed for histological examination. Treatment by CV-3611 exerted a marked inhibitory effect on the development of 3'-Me-DAB-induced hepatocellular carcinomas (HCC) as measured by multiplicity. Although less effective than CV-3611, Ca-Asc and AscP also showed inhibitory effect. We have also studied the correlation of erythrocyte (RBC) polyamine levels and HCC development. RBC polyamine levels were inhibited by Ca-Asc and its derivatives, indicating it may be a marker of hepatocarcinogenesis.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Body Weight; Carcinogens; Erythrocytes; Free Radical Scavengers; Liver; Liver Neoplasms, Experimental; Male; Methyldimethylaminoazobenzene; Organ Size; Putrescine; Rats; Spermidine; Spermine