The present experiment was performed to see the influence of phlebotomy on hematology, serum chemistry, and pathology data in rats. When normal rats received a single phlebotomy of 2 or 3 ml blood, erythrocyte count and hematocrit were slightly reduced along with a persistent depression of the blood pressure. In repeated phlebotomy studies, 0.25 to 2 ml each of blood was removed from each rat every other day for 10days. Normal rats from which 0.5 ml and more of blood was withdrawn showed decreases in erythrocyte count and serum iron level concomitant with an increase in reticulocyte count. Similar findings were obtained in rats with CCl4 liver damage or gentamicin nephrotoxicity, except that those rats hardly exhibited anemia because of a simultaneous occurrence of hemoconcentration. Histopathological findings of the liver and kidney were not different between animals with and without phlebotomy. In phenylhydrazine-treated rats receiving repeated phlebotomy, one rat in the 1-ml phlebotomy and two rats in the 2-ml phlebotomy died from severe anemia. Surviving rats receiving 2-ml phlebotomy showed higher serum GOT and GPT activities together with fatty deposition and/or focal necrosis of hepatocytes. It is concluded that every-other-day phlebotomy of up to 0.25 ml each does not significantly influence the physiological condition of normal or diseased rats.
In order to investigate the toxic effects of nivalenol, one of the trichothecene mycotoxins, we performed a short-term feeding trial for 24 days using feed supplemented with rice artificially molded with nivalenol producing fungus, Fusarium nivale Fn 2B, in female C57BL/6CrSlc SPF mice. A significant erythropenia and slight leukopenia were observed in the 30 ppm group, but no marked changes were observed in other hematological parameters, feed consumption, body weight gain, or weights of the liver, spleen, and thymus. Ultrastructural studies also revealed polyribosomal breakdowns of the bone marrow cells in the 30 ppm group.
The mutagenic potential of thiamazole, an antithyroid agent, was investigated by an in vivo cytogenetic test and was compared with those of mitomycin C and vincristin. These drugs were subcutaneously injected into slc-ICR male mice either as a single dose or as multiple doses for 5 successive days. Thiamazole (90 or 180 mg/kg) did not increase the number of micronuclei in bone marrow cells. This drug also did not induce chromosomal aberrations in spermatogonium, spermatocyte, or bone marrow cells. On the other hand, mitomycin C (3.0 mg/kg) increased the appearance of chromosomal aberrations and micronuclei. Vincristin (0.2 mg/kg) induced bone marrow cells with a so called large micronucleus (d≥D/4). These results suggest that thiamazole may not have significant effects on the genetic systems of mice.
To gain further insight into the mechanism of induction of dominant lethal mutations, the relationship between chromosome aberrations in bone marrow and in male germ cells after treatment with mitomycin C (MMC) and ethyl methanesulfonate (EMS) was examined. In addition, we obtained fertilized eggs from the oviducts of crossbred female mice in the same way as in the dominant lethal mutation test, and examined chromosome aberrations in male pronuclei. MMC 2.5 and 5.0 mg/kg, EMS 175 and 350 mg/kg were given subcutaneously to slc-ICR mice. It was concluded that MMC causes a decrease in the sperm count by killing germ cells, which in turn causes an increase in the number of unfertilized eggs and preimplantation egg loss. MMC seems also to cause invisible damages in the chromosomes of spermatocytes which lead to dominant lethality. EMS induced chromosome damage in the post-meiotic germ cells, and this damage, in turn, produced chromosome aberrations in the eggs, resulting in a high incidence of dominant lethality.
Toxicity of cyanogenetic glucoside was studied with rats using synthesized D, L-mandelonitrile-β-D-glucoside. Considering from blood cyanide level, the cause of death was presumed to be cyanide intoxication. Hydrolysis of cyanogenetic glucoside occurred mainly in small and large intestines. Cyanide level in the intestine seemed to be independent of the amount of glucoside present. LD50 value was calculated to 560 mg/kg but good dose dependent result was not obtained. Relatively rapid absorption of the glucoside from the gastrointestinal tract was observed with the highest absorption rate of 53.4% within 165 min. About 30-45% of the administered glucoside was excreted within 24 hr without alteration and dose dependence appeared in an excreted ratio. The ratio of D-mandelonitrile-β-D-glucoside to L-form excreted in the urine or remained in the gastrointestinal tract was almost in the same as at administration, and hence biological behaviors, such as absorption, excretion and hydrolysis, of both D-and L-forms of glucoside were almost the same.
The hepatotoxic effects of anesthetics brought about by their faulty intraperitoneal application was investigated. Using a syringe with a 26G needle, we injected 0.05ml/rat of a 50mg/ml solution of pentobarbital sodium directly into the livers of Sprague-Dawley rats. The animals were killed at 15, 30, or 45 minutes after injection. Massive hemorrhagic necrosis of the liver was seen in all animals injected, while focal necrosis accompanied by inflammatory cell infiltration was observed in the rats killed at 30 and 45 minutes after injection. The histological characteristics of these liver lesions were composed of three types, namely, massive hemorrhagic necrosis, focal cell infiltration separate from the necrosis, and focal necrosis with inflammatory cell infiltration. The infiltrates were composed of both neutrophils and lymphocytes. The characteristic liver lesions closely resembled the hepatic lesions produced by captopril (Helliwel et al., 1985), cyclopiazonic acid (Morrissey et al., 1985), as well as spontaneous liver lesions. The study of serum transaminase levels showed that the elevation of both SGPT and SGOT activities was correlated with the time after injection. Also, a significant increase in the total bilirubin level was noted in all animals treated.