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Biomedical subjects

I Hirono

Publications and source records attributed to I Hirono.

At least 91 records · Page 5Linked to original sources

Reproduction of acute bracken poisoning in a calf with ptaquiloside, a bracken constituent.

Acute bracken fern toxicity in a calf was reproduced with ptaquiloside, a norsesquiterpene glucoside, isolated from the boiling water extract of bracken fern. Ptaquiloside was dissolved in 500 ml of saline and administered by drench at increasing dosages for six days out of every seven for the following periods: 400 mg/day for 24 days, 800 mg/day for 14 days and 1600 mg/day for four days. Neutrophilic granulocytes began to decrease markedly around 50 days after the start of the experiment, and granulocytopenia continued for a further 35 days until the autopsy, despite the discontinuance of ptaquiloside administration. Thrombocytes showed a relatively slow depression and reached 1 X 10(5)/mm3 at the lowest level. The calf was autopsied 86 days after the start of administration of ptaquiloside. Sternal bone marrow was found to be mostly replaced with fat marrow and only small foci of erythropoietic cells and a small number of megakaryocytes remained.

Agranulocytosis↗

Separation of carcinogenic fraction of bracken fern.

Isolation of the carcinogen in the boiling water extract of bracken fern was conducted by following the active principle with a carcinogenicity bioassay. Fractionation of the bracken extract was carried out using adsorption on resin (Amberlite XAD-2 and TOYOPEARL HW-40 (c] and organic solvent extraction. A diet containing each of the fractions was given to 7 female Charles River Sprague-Dawley rats (CD rats) of 4 weeks old, except for the second fraction. All 7 rats given the last carcinogenic fraction developed mammary and intestinal tumors and 5 rats had urinary bladder tumors. Ptaquiloside (PT) which induced mammary cancer in female CD rats and rho-hydroxystyrene glycosides were isolated from this fraction.

Animals↗

Hyperplastic nodules of the liver induced in rats fed bracken diet.

Hyperplastic nodules (HN) of the liver were induced in Charles River Sprague-Dawley rats (CD rats) and ACI rats fed a diet containing 30% bracken for 260 and 180 days, respectively. HN were also induced in high incidence in CD rats fed a diet containing the carcinogenic fractions of bracken extract.

Animals↗

Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays.

The sulfated polysaccharides degraded carrageenan and dextran sulfate sodium were studied for genotoxicity using DNA repair tests employing cultured rat hepatocytes or intestinal mucosal cells. No evidence of unscheduled DNA synthesis was obtained. In addition, both alone and in combination with the comutagen norharman, these substances were nonmutagenic in the Salmonella microsome/mutagenicity test. These findings suggest that the carcinogenicity of the sulfated polysaccharides may be due to nongenotoxic mechanisms.

Animals↗

Induction of hepatic ornithine decarboxylase by intraperitoneal administration of caffeine in rats.

I.p. administration of caffeine led to a significant increase in hepatic ornithine decarboxylase activity in rats. The enzyme activity reached approximately 10-fold above the control level 5 h after the injection of caffeine at a dose of 150 mg/kg body weight. The high level of ornithine decarboxylase activity remained for 3 h and then decreased rapidly. The enzyme activity of the kidney, however, was not significantly enhanced by the administration of caffeine. The possible mechanism of the caffeine-mediated hepatic ornithine decarboxylase induction is discussed.

Animals↗

Quantitative determination of the superoxide radicals in the xanthine oxidase reaction by measurement of the electron spin resonance signal of the superoxide radical spin adduct of 5,5-dimethyl-1-pyrroline-1-oxide.

Reactivities of biologically active compounds with superoxide radicals were examined by measurement of electron spin resonance (ESR) spectra of 5-hydroperoxy-2,2-dimethyl-1-pyrrolidinyloxyl formed from 5,5-dimethyl-1-pyrroline-1-oxide and the superoxide radicals generated by xanthine-xanthine oxidase system. Quantitative determination of the superoxide radicals was performed by comparing the intensity of the spin adducts with that of 4-hydroxy-2,2,6,6-tetramethyl-pipperidinooxyl whose spin concentration was determined. Methyl viologen enhanced the formation of this spin adducts, while, rutin and luteoskyrin prevented it.

Cyclic N-Oxides↗

Interaction between quercetin and superoxide radicals. Reduction of the quercetin mutagenicity.

Interaction between quercetin and superoxide radicals was investigated using xanthine-xanthine oxidase system and potassium superoxide as superoxide radical generators. Superoxide radical scavenging action of quercetin was demonstrated by measurement of the electron spin resonance spectrum of the 5-hydroperoxy-2,2-dimethyl-1-pyrrolidinyloxyl adduct. Degradation of quercetin by the radicals was demonstrated spectrophotometrically. Reduction of the quercetin mutagenicity by the radicals was demonstrated in the Salmonella typhimurium strain TA 98 by the Ames test.

Animals↗

Some toxic properties of a carcinogenic pyrrolizidine alkaloid, petasitenine.

Some toxic properties of petasitenine, a hepatocarcinogenic pyrrolizidine alkaloid, were confirmed in 3 parts of studies. Electron microscopic observation of rat liver on the stage of acute toxicity following administration of a toxic dose of petasitenine disclosed the distinctive changes i.e., nucleolar segregation, degradation of endoplasmic reticulum such as formation of concentric whorls in the liver cells. Biochemical test for the mitochondrial function in the isolated mitochondria from rat liver cells revealed on inhibitory effects of petasitenine in the respiratory system, indicating that minor changes of mitochondria on the pyrrolizidine alkaloid may be induced by some other indirect factor. Investigation for the effect of petasitenine on the cell cycle of the cultured cell line from the human carcinoma showed some inhibitory effects in the appearance of cells in S-phase or M-phase, suggesting a possibility that toxicity of petasitenine will be developed in the tissues other than the liver or in the species apart from rodents.

Animals↗

Lack of promotive effect of quercetin on methylazoxymethanol acetate carcinogenesis in rats.

Promoting effect of quercetin in the intestinal tract was examined in Sprague-Dawley strain rats. The rats were injected with methylazoxymethanol acetate (MAM) in saline solution at 25 mg/kg body weight once a week for 3 weeks and fed a diet containing 1% quercetin for the following 459 days. Most tumors found in this experimental group were also found in the group injected with MAM alone and there was no significant difference in tumor incidence between these two groups. No tumors were found in the group fed the 1% quercetin diet alone. Thus, quercetin was shown to lack of promoting activity on MAM-induced intestinal carcinogenesis in Sprague-Dawley rats.

Animals↗

Carcinogenicity in rats of ptaquiloside isolated from bracken.

The nature of the carcinogen present in bracken fern has not yet been elucidated. Very recently, we succeeded in isolating ptaquiloside, a novel norsesquiterpene glucoside of the illudane type, from bracken. Ptaquiloside was shown to be a carcinogenic principle of bracken fern. It induces mammary cancer and multiple ileal tumors in high incidences when given orally to female Sprague-Dawley rats.

Animals↗

Suppressive effect of caffeine on the development of hepatic tumors induced by 2-acetylaminofluorene in ACI rats.

The effect of caffeine on the development of hepatic tumors induced by 2-acetylaminofluorene (2-AAF) was studied in 6-week-old male ACI rats. Rats in group 1 were fed a diet containing 0.02% 2-AAF for 18 weeks and then basal diet for 15 weeks with normal drinking water throughout. Animals in group 2 received a diet containing 0.02% 2-AAF and a solution of 0.2% caffeine as their drinking water for 18 weeks, followed by basal diet and caffeine-free water. Rats in group 3 received drinking water containing 0.2% caffeine for 18 weeks. Rats in group 4 were given a basal diet and water freely and served as controls. The experiment was terminated after 33 weeks. Both the multiplicity, i.e. the number of tumors per rat, and the size of tumors were less (P less than 0.001 in the former case, by Student's t-test) in group 2 than in group 1. Thus, the induction of tumors of the liver by 2-AAF was suppressed by the administration of caffeine.

2-Acetylaminofluorene↗

Carcinogenic activity of Farfugium japonicum and Senecio cannabifolius.

The carcinogenicity of Farfugium japonicum and Senecio cannabifolius was studied in ACI rats. In Group I, rats were given a diet containing 20% Farfugium japonicum. Groups II, III, IV and V were given diets containing 8%, 4%, 1% and 0.2% Senecio cannabifolius until the end of the experiment, respectively. The experiment was terminated after 480 days, except for Group V which was terminated 560 days after the start of feeding. Hemangioendothelial sarcoma of the liver and liver cell adenoma were induced in Groups I, IV and V. All rats in Groups II and III died of hepatotoxicity within a short period.

Adenoma↗

Carcinogenicity of dextran sulfate sodium in relation to its molecular weight.

The carcinogenicity of dextran and 3 kinds of dextran sulfate sodium with different molecular weights and almost the same sulfur content were compared in ACI rats. Dextran sulfate sodium of molecular weight 54,000 showed a strong carcinogenic activity when it was given orally as 2.5% diet, whereas dextran sulfate sodium of molecular weight 520,000 and 9500 and dextran showed no significant carcinogenicity, i.e. the peak of carcinogenic activity of dextran sulfate sodium appeared at molecular weight 54,000, and dextran sulfates with larger or smaller molecular weights had no carcinogenic activity.

Adenocarcinoma↗

Carcinogenicity examination of betel quid. II. Effect of vitamin A deficiency on rats fed semipurified diet containing betel nut and calcium hydroxide.

The effect of vitamin A deficiency on the carcinogenicity of betel quid was studied, using long-term feeding of vitamin-A-deficient and -sufficient diets with and without betel nut and calcium hydroxide in ACI rats. A high incidence of focal epithelial hyperplasia was observed in the upper digestive tract (tongue, buccal oral mucosa, esophagus, and forestomach) of rats in the group given the vitamin-A-deficient diet mixed with betel nut and calcium hydroxide. The vitamin-A-deficient group also showed a high incidence of squamous papilloma in the tongue, buccal mucosa, and forestomach. The incidence of hyperplastic lesions of the tongue and buccal oral mucosa was significantly higher in this group than in the group receiving the vitamin-A-sufficient diet with betel nut and calcium hydroxide. These results suggest that the vitamin-A-deficient condition enhanced the growth of epithelial hyperplasia that was due to the administration of the betel quid ingredients. However, vitamin A did not protect against the development of altered liver cell foci, which were frequently seen with a small number of hepatocellular neoplasms in all groups given the diets containing betel nut and calcium hydroxide (both vitamin-A-deficient and -sufficient groups).

Animals↗

Induction of mammary cancer in CD rats fed bracken diet.

Fifteen male and 15 female Charles River Sprague-Dawley rats (CD rats) of 6 weeks old were given a diet containing 30% bracken fronds throughout the experimental period of 260 days. Male rats fed bracken diet developed multiple ileal tumors and urinary bladder tumors with incidences of 100% and 60%, respectively. Female rats developed multiple mammary tumors with an incidence of 87% in addition to ileal and urinary bladder tumors. The earliest mammary tumor was detected on day 78, and the last on day 256. The average number of tumors per rat was 5.6. Most mammary tumors were papillary carcinomas and adenocarcinomas. No tumors were found in rats in the control group.

Adenocarcinoma↗

Enhancing effect of dextran sulfate sodium on colorectal carcinogenesis by 1,2-dimethylhydrazine in rats.

Four groups were used, each consisting of 24 male ACI rats. Group I received a single subcutaneous injection of 20 mg 1,2-dimethylhydrazine (DMH)/kg body weight and was fed on basal diet until the termination of the experiment. Group II received the same single injection as in group I and then, starting one week later, was fed the diet containing 1% dextran sulfate sodium (DS-M-1). Group III received an injection of 0.9% sodium chloride and then DS-M-1 diet. The control group was given neither DMH nor DS-M-1 diet. The experiment was terminated after 40 weeks. A significantly higher incidence of colorectal carcinoma was observed in group II, as compared with group I (P less than 0.02). These data demonstrate the enhancing effect of DS-M-1 on colorectal carcinogenesis.

1,2-Dimethylhydrazine↗