The effects of cisplatin on erythropoietin (EPO) production were investigated in comparison with the effects of phenylhydrazine in rats. Cisplatin (4.5 mg/kg i.p. bolus) decreased red blood cell count (RBC), hematocrit (Hct) and hemoglobin concentration (Hgb) for 14 days after dosing. These decreases were accompanied with increases of blood urea nitrogen (BUN) and serum creatinine (s-CRE). Both serum EPO concentration and kidney EPO mRNA content were significantly decreased in cisplatin-treated rats. On the other hand, phenylhydrazine (10 mg/kg p.o. once a day for 8 days) decreased RBC, Hct and Hgb, and increased serum EPO concentration and kidney EPO mRNA content. Phenylhydrazine had little effect on BUN or s-CRE. These results suggest that a suppression of EPO production is involved in the pathophysiology of cisplatin-induced renal anemia and that measurement of serum EPO concentration and kidney EPO mRNA content is available for distinguishing renal anemia from hemolytic anemia.
The present study was conducted to evaluate the variations in the normal auditory brainstem response (ABR) between the F344 and Wistar rats. It was also investigated whether strain differences exist in the ABR profiles of each strain of rat given furosemide, which induced ototoxicity. The typical waveform of ABRs in the F344 rats were similar to those observed in the Wistar rats. There were no significant differences between the strains in almost all parameters, but peak latencies from P1 to P3 in the F344 rats tended to be longer than those in the Wistar rats. After a single intravenous injection of furosemide, the minimum effective dosage levels, at which each peak of the ABR disappeared, were 53.3±8.2 and 70.0±8.9 mg/kg in the F344 and Wistar rats, respectively. A single intravenous injection of 100 mg/kg furosemide delayed the reversal of decrease in amplitude, prolongation of peak latency and the reappearance time in F344 rats. Thus, the normal waveform of ABR was comparable in the F344 and Wistar rats, but a tendency towards a prolongation in each latency was noted in the F344 rat. The results also suggested that the ABR of F344 rats were more vulnerable to furosemide ototoxicity than that of Wistar rats.
Zinc, copper and iron levels of tissues in rats or beagle dogs were measured after a 13- or 52-week toxicity study of polaprezinc, which contains a zinc element; The zinc content in almost all rat tissues remarkably increased with a conspicuous decrease of copper and various changes of iron at doses of 600 mg/kg/day or more. Zinc and copper levels increased and decreased respectively, at 300 mg/kg/day. At a dose of 150 mg/kg/day, there was a slight increase of zinc in some tissues at 52-weeks, but no copper decrease. The results obtained from beagle dogs differed somewhat from that in rats. Dogs treated with polaprezind at 50 mg/kg/day or more accumulated zinc in some tissues. A copper decrement was seen only in the liver and heart from the group given 300 mg/kg/day, whereas copper levels in the kidney of all treated groups were higher than that in the controls suggesting that canine polaprezinc toxicity is due to direct zinc toxic effects.
Modifying effects of benzyl isothiocyanate (BITC), a glucosinolate compound, were investigated on 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)-induced mammary carcinogenesis in female SD fats. One hundred twenty five female rats were divided into 4 groups. Starting at 6 weeks of age, rats were fed high fat diet containing 23.5% corn oil (Groups 1 and 4) or the experimental diet (high fat diet with 400 ppm BITC) (Groupd 2 and 3). At 7 weeks of age, Groups 1 and 2 were given PhIP (100 mg/kg body weight, 8 times for 16 days) by intragastric tube. One week after the final PhIP treatment, the experimental diet for Groups 2 and 3 switched to high fat diet. At the termination (31 weeks after the start of experiment), mammary adenocardinomas were recognized in Group 1 (PhIP alone) and Group 2 (PhIP + BITC). The incidende of neoplasms was 74.2% in Group 1, and 62.5% in Group 2. The multiplicity of them was 1.71±1.70 in Group 1, and 1.91±2.94 in Group 2. Mean sizes of tumors were 9.9±7.1 mm in Group 1, and 10.8±6.8 mm in Group 2. But no significant different as for tumors were available between the two groups. These results imply that the glucosinolate compound does not have clear inhibitory effects on PhIP-induced mammary carcinogenesis in rats.
The oral toxicity of capsaicin was investigated in mice and rats. Oral LD50 values were 118.8 mg/kg for male and 97.4 mg/kg for female mice, and 161.2 mg/kg for male and 148.1 mg/kg for female rats. Major toxic symptoms in mice were salivation, erythema of skin, staggering gait, bradypnea and cyanosis. Some animals showed tremor, clonic convulsion, dyspnea and lateral or prone position and then died 4 to 26 min after dosing. Survivors recovered within 6 hr in mice and 24 hr in rats. Toxic symptoms of fats were almost the same as mice, but rats showing higher incidence of cyanosis, clonic or tonic convulsion, dyspnea and lateral position, and the recovery was later than mice. The cause of death by capsaicin may be due to hypotension and respiratory paralysis in both animals, although the pathophysiology of death is not clearly understood. At pathological examination, erosion and ulcer of gastric fundus were seen in dead animals, while no pathological change was seen in surviving ones.