Effect of nicotine on chemiluminericence (CL) responses of human polymorphonuclear leukocytes (PMN) in vitro was investigated. Nicotine, ranging from 10-5 to 5×10-4 M, showed a concentration-dependent inhibition of the CL induced by 2.5 mg of opsonized zymosan. This inhibitory effect of nicotine (10-4 M) on CL was not affected by atropine (10-4 M), hexamethonium (10-5 M) or acetyl β-methylcholine (10-4 M). These results indicate that nicotine directly acts to PMN with no relation of cholinergic affecting receptors. As to cytotoxic effects on PMN, assessed by the methods of trypan blue exclusion and of lactate dehydrogenase leakage from the cells, nicotine showed no cytotoxic effect on PMN in its range of 10-5 to 5×10-4 M. It is concluded that tobacco alkaloid nicotine could directly inhibit phagocytizing function of PMN. Furthermore, it is presumed that PMN circulating in the respiratory organs in tobacco smoking would be exposed to high concentrations of nicotine, and that the nicotine incorporated into the circulating system could suppress PMN functions resulting in harmful influences on the host defense mechanisms.
Effects of long-term exposure to sublethal concentration (300-350ppm) of carbon monoxide (CO) on the distribution of methylmercury (MeHg) in the blood and organs of mice were examined using 6th week-old ICR mice of both sexes. Firstly, female mice were exposed to CO immediately after single ip injection of CH3HgCl (1 mg/kg). At the earliest stage, brain mercury level was higher in CO mice than in control mice, while blood mercury level was lower in CO mice than in control mice. There were indications that compensatory hemoconcentration and resultant increase of mercury levels in the blood, brain and liver occurred in CO mice by the 8th day of CO exposure. Mercury in the blood, brain, liver and kidney decreased more rapidly in CO mice than in control mice for a short period after hemoconcentration had occurred. Secondly, male mice were pre-exposed to CO for 7 days, received single ip injection of CH3HgCl (1 mg/kg) and were re-exposed to CO for an additional 21 days. Hemoconcentration, increased mercury levels in the blood, brain and liver were observed in CO mice. Thirdly, male mice were pre-exposed to CO for 7 days, administered po with CH3HgCl (2 mg/kg) and re-exposed to CO for 24 hr. Mercury levels in the blood, brain and liver but not the kidneys were higher in CO mice than in control mice. The relationships between hemoconcentration and MeHg distribution in vertebrates were discussed.
Unscheduled DNA synthesis (UDS) induced by in vitro exposure to five alkylating carcinogens was measured in the mucosal cells from three different sites of the rat intestine. The yield of UDS by N-methyl-N'-nitro-N-nitrosoguanidine or N-ethyl-N'-nitro-N-nitrosoguanidine or methylazoxymethanol acetate was higher in the cells of colon & rectum than in those of the jejunum or ileum. Conversely, UDS induction by N-methyl-N-nitrosourea or methyl-methanesulphonate was seen at a rather higher level in the cells from the small intestine compared with those from the colon & rectum.
Male ICR mice were given dietary Cd at three different levels (50, 100 and 200 ppm) for 85 days. At the end of this period, they showed a marked accumulation of Cd in the liver and kidney. In addition, there was also an increase in Zn and a decrease in Fe in these organs. The concentration of Cu in these organs; however remained unchanged. Serum cholesterol decreased in the Cd-100 and Cd-200 groups, but hepatic cholesterol did not. There was a positive correlation between serum cholesterol and serum Cu or Zn but not between serum cholesterol and serum Zn/Cu. Serum triglyceride was increased slightly but not dignificantly by the Cd exposure. A significant negative correlation between serum and hepatic triglyceride was found. These alterations of serum and hepatic lipids were discussed in relation to the essential metals (Cu, Zn and Fe).
Delayed neurotoxicity experiment was carried out on an organophosphorus compound (TOCP) in hens. Fifteen hens, 1.9 kg of their average body weight and 20 months of age, were orally administered with TOCP in a dose of 400 mg/kg body weight. Two animals out of 15 were sacrificed after 7 days to examine alterations in the nervous system under electron microscope. On the remaining 13 animals, histopathological examinations were carried out after 35 days. During the course of the experiment, progressive neuropathy developed in the animals at 10 to 12 days after the exposure to TOCP. Examinations of the sciatic nerve under electron microscope revealed slight axonal degeneration while the myelin sheath was found to be rather intact. On the animals after the observation periods of 35 days, marked axonal and myelin degeneration was observed in the anterior and posterior funiculus, and in the spinocerebellar tracts of the spinal cord as well as in the cerebellar peduncle and in the white matter of the cerebellum associated with glial proliferation. The localization and degree of these changes were considered to be "Dying Back", showing systemic neuropathy. Moreover, the morphological alterations of the nerve cells were observed in the Purkinje cells, in the cerebellar nucleus, gracilis nucleus, and anterior horn cells of the lumbar spinal cords, characterized by loss of nerve cells and/or tigrolysis. Muscular lesions showed small group atrophy, corresponding to Type I fiber atrophy.
The total and differential Cell counts of femoral bone marrow and peripheral reticulocyte counts were determined in male ddY mice up to day 11 after an intraperitoneal injection of 2 mg/kg of mitomycin C. 1. Total marrow cell counts showed a minimum value on day 2 after the injection, and then recovered to the control level on day 7. 2. In the differential cell counts, the minimum values were observed on day 1 for proerythroblasts and basophilic erythroblasts, on day 2 for polychromatic erythroblasts, and on day 4 for mature neutrophils. Recovery was seen from the 4th to 7th days after injection. Marrow lymphocytes showed a maximum value when the total counts were minimum. 3. The peripheral reticulocytes almost disappeared 4 days after the injection, and recovered to the pretreatment level on day 11.
The acute toxicity test of garlic extract was studied in Wistar rats and ddY mice. The LD<50> values of garlic extract by P.O., I.P. and S.C. administration were estimated over 30 ml/kg respectively in male and female of both rodents. In 30 ml/kg of I.P. group, five of ten in male rats and one of ten in female rats were died within a day after administration, however no specific signs due to garlic extract were observed in survivals for 7 days.
The influence of garlic extract on the chronic toxicity test were examined orally in Wistar rats for 6 months. There were no toxic symptoms due to garlic extract even at dose level of 2000 mg/kg for 5 times a week during 6 months. High dose of garlic extract did not inhibit the body weight gain, while the food consumption decreased slightly for the nutritional effects of it in both male and female rats. There were no significant differences in urinary, hematological and serological examinations compared each groups. In the histopathological findings, no toxic signs were observed on any of the tissues and organs examined.
Mutagenicity and cytotoxicity of fresh juice and alcohol extract from garlic were studied by Ames' test, Rec assay, Micronucleus test and the check of the influence to HEp-2 and chinese hamster embryo (CHE) primary cultured cells. No evidence of mutagenicity of these samples were observed in Ames' test and Rec assay, while there was dose dependent increase of micronucleated cells and polychromatocytes on the bone marrow cells of mice and chinese hamsters treated with garlic juice. There were severe damages, e.g. growth inhibition and morphological changes of both cultured cells due to garlic juice, but no or slightly cytotoxic signs were observed even in high concentration of garlic extract. A higher sensitivity to the cytotoxic effects of garlic was seen by the present findings with CHE primary cells than HEp-2 cell line.
Acute toxicities of Amfenac sodium (AHR-5850), new non-steroidal anti-inflammatory agent, were studied in mice and rats. Each value of LD50 by oral, sc, im, iv and ip administration with this compound was 1190, 580, 540, 550 and 790 mg/kg for male mice and 1450, 625, 610, 630 and 710 mg/kg for female mice, respectively. Rats showed higher lethality than mice. There was no significant difference of sex in the values of LD50 for mice and rats. movement and respiration rate followed by gastrointestinal ulcer, secondary peritonitis and systemic emaciation. These results suggest that the death is caused by secondary petitonitis and systemic emaciation due to gastrointestinal ulcer.