Employing propranolol as a non-selective beta-blocker, atenolol, acebutolol and metoprolol as selective betal-blockers, butoxamine as a selective beta2-blocker, labetalol as an alpha- and beta-blocker, and phentolamine as an alpha-blocker, we compared the effects of these adrenoceptor-blocking agents to reduce the degree of the myocardial injury induced by epinephrine in mice. Epinephrine in a single dose of 4mg/kg/day, s.c., daily for 7 days, caused widely extended lesions, necrosis and fibrosis in the myocardial fibers, and degeneration in the residual myocaridal fibers. The adrenoceptor-blocking agents in a dose of 10mg/kg/day, s. c., given 30 minutes prior to epinephrine to each mouse daily for 7 days, had reduced the degree of the myocardial injury induced by epinephrine. The blockers, all, effectively suppressed the injury. Although metoprolol and butoxamine were less effective on the protection of the cardiotoxicity than phentholamine, the other blockers prevented the cardiotoxicity with the same degree as phentolamine did. These findings suggest that not only alpha- but also beta1- and beta2-adrenoceptors play critical roles in producing the myocardial injury.
The effect of chlorpromazine (CPZ) administration before mating on reproduction was studied using male and female Sprague Dawley strain rats, and was evaluated over three generations. CPZ in dose of 12.5, 25, 50 and 100 mg/kg was orally administered to both male and female rats (F0 generation) every day for 2 weeks before mating with the following results : 1) The incidence of insemination and pregnancy of the F0 generation rats decreased but did not decrease in the F1 generation. While no influence of CPZ on the number of myometrial glands, on the length of pregnancy or on delivery was noted in either the F0 or F1 females, the number of surviving fetuses and newborns decreased in a dose-dependent fashion. 2) The body weight of rats in the F0 and F1 generations decreased depending on the dosage of CPZ, but the body weight of the F2 generation increased. 3) The wet weight of the major organs of the male and female rats in the F0 generation was affected by CPZ when administered at 100 mg/kg. The weight of the adrenal, pituitary and prostate glands in males, the adrenal gland and ovary in females increased, whereas the weight of the pituitary and uterus in females decreased. These results suggest that administering CPZ to the F0 rats before mating exerts an influence on the reproduction in both the F0 and F1 generations.
A rapid microassay for hemolytic antibody using an automatic spectrophotometer was developed. This microassay was parallel to hemolytic plaque forming cell (PFC) assay most commonly used to detect antibody formation. The former had more advantages than the latter did. The data obtained using arsenic and some metallic compounds as immunomodifiers suggested that this microassay was suitable for the screening of immunomodifiers in immunotoxicological and immunopharmacological studies which deal with a large number of samples within limiteid time.
Bilobol, isolated from ginkgo fruit pulp, has been noted to be a strong skin irritant like 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoter in the skin. A comparative investigation of morphological changes induced by bilobol and TPA induced in the skin of CD-1 mice, and an assessment of the skin tumor promoting potential of bilobol were therefore performed. In experiment I, mice received a single application of 2.5, 50 or 1000 μg of bilobol, or 0.1 or 2.5 μg of TPA on the right ear. The 50 or 1000 μg bilobol and 2.5 μg TPA doses caused ear redness, epidermal thickening and inflammatory infiltration. The dose of 2.5 μg of TPA, which is usually used as tumor promoter in skin carcinogenesis, was equivalent to 50 μg of bilobol in irritant effect. Thus, 50 μg of bilobol was used for the promotion testing (experiment II) in CD-1 mice initiated with 100 μg of 7, 12-dimethylbenz[a]anthracene (DMBA). Treatment with either 10 or 50 μg bilobol twice a week for 30 weeks did not result in any tumor development, thus suggesting that bilobol is not a complete promoter of skin carcinogenesis, despite generation of inflammation.
The effects of Bifemelane (BF) on lipid perokidation, the activities of hepatic drug metabolizing enzymes, and the function of cell membranes were examined in rats. In the liver ischemia-reperfusion model, BF suppressed the elevation of the lipid peroxidation level during the period of reperfusion. BF did not exhibit a radical-trapping action using a stable free radical, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), which was estimated by electron spin resonance (ESR). BF remarkably inhibited NADPH-dependent lipid peroxidation in vitro. BF had no effect on the contents of cytochrome P-450 and b5 and the activities of NADPH cytochrome P-450reductase and Cu, Zn-superoxide dismutase (SOD). BF suppressed phorbol myristate acetate (PMA)-induced superoxide formation of polymorphonuclear leukocytes (PMNs), protected hypotonic hemolysis of erythrocyte and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and serum phospholipase A activity. These results suggest that BF has neither radical-trapping activity nor any influence on the drug metabolizing enzymes, but BF has a membrane-stabilizing action and it attributes to the suppressive effect of lipid peroxidation.