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Biomedical subjects

S B Hooser

Publications and source records attributed to S B Hooser.

32 records · Page 2Linked to original sources
PubMed1989

Toxicity of microcystin LR, a cyclic heptapeptide hepatotoxin from Microcystis aeruginosa, to rats and mice.

Rats (Sprague-Dawley) and mice (Balb/c) were given microcystin LR intraperitoneally and were killed at intervals up to 24 hr (rats) or 90 min (mice) and necropsied. The lowest consistently lethal dose was 160 micrograms/kg in rats and 100 micrograms/kg in mice. Rats that were clinically unaffected had no lesion. All clinically affected rats in all dose groups died (from 20 to 32 hr after toxin) and had similar hepatic lesions. Livers were enlarged and dark red beginning 40 to 60 min after toxin. Mild disassociation and rounding of centrilobular hepatocytes developed within 20 min. By 60 min after toxin, degeneration and necrosis of hepatocytes involved most of the lobules except for small periportal zones. Weights of livers and kidneys were significantly increased. Eosinophilic fibrillar material filled renal glomerular capillaries as early as 9 hr after toxin. At 18 to 24 hr there was moderate vacuolation of proximal tubular epithelium with mild tubular dilatation. Beginning at 1 hr, intact hepatocytes and hepatic debris were present in pulmonary vessels. Analysis of serum revealed an increase in alanine aminotransferase 40 min after toxin; at 6 to 12 hr there were significant increases in alkaline phosphatase, total bilirubin, blood urea nitrogen, and creatinine. Mice survived only 60 to 90 min after toxin. Hepatic lesions were similar to those in rats, but renal and pulmonary lesions were not seen.

Animals↗
PubMed1988

Toxicologic evaluation of chlorpyrifos in cats.

Twenty-four male domestic shorthair cats were used to evaluate the acute and chronic effects of a single, toxic but sublethal, orally administered dose of chlorpyrifos. A dosage of 10 mg/kg of body weight did not induce clinical signs of toxicosis, but a dosage of 40 mg/kg induced clinical signs of toxicosis, and 1 of 12 cats died. Chlorpyrifos given at a dosage of 0.1 mg/kg to 2 cats reduced whole blood and plasma cholinesterase (Che) activities to values obtained after cats were given doses that induced clinical signs of toxicosis. Regeneration time for whole blood and plasma Che activities ranged from 7 to 28 days. Brain Che activity was considerably decreased in 1 cat that died 4.5 hours after dosing, but was normal in all others at 28 days after dosing. Other than decreased Che activity, significant changes were not seen in hematologic or serum biochemical values. Toxin-related lesions were not seen during macroscopic or microscopic examination.

Acetylcholinesterase↗
PubMed1987

Blue-green algae (Microcystis aeruginosa) hepatotoxicosis in dairy cows.

Twenty cows from a dairy herd consisting of 60 healthy, lactating Holsteins developed clinical signs of anorexia, mental derangement, dehydration, recumbency, and ruminal atony after ingesting water containing blue-green algae. Of the 20 cows, 9 died. The algal bloom, which developed in a stagnant pond during hot, dry weather, was identified as the cyanobacterium Microcystis aeruginosa, a potentially hepatotoxic algae. One week after the onset of toxicosis, affected cows seemed healthy, although liver-associated enzyme activities (alkaline phosphatase, gamma-glutamyl transferase, aspartate transaminase, and lactate dehydrogenase) were increased. Intraruminal administration of the intact wet bloom to a healthy 125-kg Angus heifer was followed by hepatic necrosis and death. The liver was large, friable, and gun-metal blue, with microscopically evident hepatocyte dissociation, degeneration, and necrosis. The ingesta of the heifer contained typical clumps of cells that were identified as M aeruginosa. The intraperitoneal administration of lyophilized cell material from that bloom to 18 mice caused marked hepatic enlargement. The intraperitoneal median lethal dose of the dried bloom was estimated to be 10 mg/kg of body weight. A cyclic peptide toxin purified from the algae seems to be similar structurally to toxins from other characterized hepatotoxic blooms of M aeruginosa.

Animals↗
PubMed1986

Effects of an insecticidal dip containing d-limonene in the cat.

A study was undertaken to determine the effects of a single dermal application of a commercial insecticidal dip containing 78.2% d-limonene in cats. At the manufacturer's recommended concentration of 1.5 oz/gal of water, no clinical signs or lesions of toxicosis were seen. At 5 times the recommended concentration, clinical signs were mild and consisted of hypersalivation of short duration, ataxia, and muscle tremors resembling shivering. At 15 times the recommended concentration, clinical signs included hypersalivation lasting 15 to 30 minutes, moderate-to-severe ataxia lasting 1 to 5 hours, muscle tremors resembling shivering lasting 1 to 4 hours, and severe hypothermia beginning soon after treatment and lasting 5 hours. Gross lesions were confined to excoriation of the scrotal and perineal areas of the treated male cats at the 15 X concentration. No deaths or other lasting effects were seen at any dosage.

Animals↗
PubMedDate not supplied

Long-term ovarian and gonadotropin changes in mice exposed to 4-vinylcyclohexene.

This study investigated the relationships between 4-vinylcyclohexene-induced follicular destruction, plasma FSH levels, and the development of ovarian preneoplastic changes. Female, 28-day-old, B6C3F1 mice were administered VCH (800 mg/kg/day, ip) or sesame seed oil, ip daily for 30 days. At 30, 60, 120, 240, and 360 days following the beginning of treatment, groups were killed, their ovaries were harvested, and plasma was collected for measurement of FSH. Ovarian weight was less and oocytes contained in preantral follicles were significantly fewer than controls at all time points. Plasma FSH concentrations in VCH-treated animals were increased significantly above controls at 240 d and 360 d. Histologically, there was oocyte loss at all times, whereas at 240 and 360 days, small to medium, irregularly shaped foci of hypertrophic cells were present. In addition, at 360 days 80% of the VCH-treated mice had a 1- to 2-mm, blood-filled cystic structure present in one or both ovaries. These studies indicate that VCH-induced oocyte destruction and follicle loss are associated with increases in plasma FSH, are associated with ovarian failure at 360 days, and are temporally related to ovarian cellular hypertrophy and the formation of blood-filled cystic ovarian structures. These events are possibly related to ovarian neoplasms produced by long-term exposure to VCH.

Androstenedione↗
PubMedDate not supplied

Testicular germ cell toxicity caused by vinylcyclohexene diepoxide in mice.

Vinylcyclohexene diepoxide (VCD) produces ovarian toxicity in female mice and rats, whereas testicular damage occurs only in mice. The objectives of these studies were to determine the target cell(s) and spermatogonial survival following VCD administration. In addition, the effects of 4-vinylcyclohexene (VCH) and two epoxide metabolites, vinylcyclohexene 1,2-monoepoxide and VCD were compared. Male mice were dosed daily with VCD (320 mg/kg/d, i.p.) and killed at 5, 10, 15, 20, 25, or 30 d. Two groups were dosed daily for 30 d and allowed to recover for 30 or 60 d. Decreases in testis weight began at 5 d and continued to 30 d. These decreases corresponded to progressive necrosis of germ cells. After 5 d of VCD, there was loss of Type I and B spermatogonia in Stages II to VI and of preleptotene spermatocytes in Stages VI to VIII. After 30 d of dosing, seminiferous tubules were devoid of germ cells except for spermatogonial stem cells. Following 30 d of recovery, 100% of the seminiferous tubules were repopulated. Epididymal spermatozoa were present after 60 d of recovery. Increasing doses of VCD (0 to 320 mg/kg/d) resulted in increasing testicular toxicity. Neither VCH (800 mg/kg, i.p.) nor VCM (200 mg/kg, i.p.) caused testicular damage. VCD administration initially results in destruction of spermatogonia and spermatocytes, which are undergoing DNA synthesis and cell replication, followed by loss of maturing cells. Neither VCH nor VCM caused testicular germ cell destruction, although all three compounds destroy germ cells in female mice. Therefore, further investigation will be necessary to understand these differences in chemical-induced toxicity between ovaries and testes.

Animals↗
PubMedDate not supplied

Taxines: a review of the mechanism and toxicity of yew (Taxus spp.) alkaloids.

This literature review summarizes relevant information and recent progress regarding the scientific investigations of taxine alkaloids. Taxines are the active, poisonous constituents in yew plants (Taxus spp.) and have been implicated in animal and human poisonings. Several taxine alkaloids have been isolated and characterized through the use of high performance liquid chromatography, mass spectroscopy, and nuclear magnetic resonance. Recently, as a result of electrophysiological investigations, significant progress has been made with regard to their pharmacological and toxicological mechanisms of action. Current investigations suggest that their chief action is on cardiac myocytes resulting in heart failure and death in instances of animal and human poisoning.

Alkaloids↗
PubMedDate not supplied

Ovarian toxicity of 4-vinylcyclohexene and related olefins in B6C3F1 mice: role of diepoxides.

4-Vinylcyclohexene (VCH) is an ovarian toxicant in mice. Studies have established that bioactivation of VCH to epoxides is required for its ovotoxicity, with vinylcyclohexene diepoxide being the most potent epoxide of VCH in terms of follicular depletion. To determine the role of the diepoxide in the ovarian toxicity of VCH and related compounds, a structure-activity study was conducted. Following administration (ip) of VCH for 30 days, a significant depletion of ovarian follicles was observed. No alteration of small ovarian follicle counts occurred following treatment with structural analogues of VCH (vinylcyclohexane, ethylcyclohexene, and cyclohexene) that contain only a single unsaturated site. These VCH analogues were converted to monoepoxides both in vitro and in vivo. In addition, when the monoepoxide forms of the VCH analogues were administered to mice, they were not ovotoxic. These results indicate that vinylcyclohexene diepoxide may be the ultimate ovotoxic metabolite of VCH. A diepoxide was also shown to be critical for butadiene- and isoprene-induced follicular loss. Butadiene monoepoxide, butadiene diepoxide, and isoprene were ovotoxic. In contrast, the monoepoxide, epoxybutane, was not ovotoxic. The ovotoxicity of these compounds correlated with their chemical reactivity as assessed by alkylation of nicotinamide. Vinylcyclohexene diepoxide and butadiene diepoxide had a 3.5- to 10-fold higher chemical reactivity as compared to their monoepoxide precursors and structurally related monoepoxides. Thus, a relationship exists between chemical reactivity and ovotoxicity. Only those compounds which are metabolized to a diepoxide or are a diepoxide were ovotoxic. The formation of these diepoxide metabolites may in turn be linked to the ovarian toxicity and carcinogenicity of these olefins.

Alkenes↗
PubMedDate not supplied

Fulminant hepatocyte apoptosis in vivo following microcystin-LR administration to rats.

Microcystin-LR (MCLR) is a cyanobacterial toxin responsible for human and livestock deaths worldwide. MCLR has also been implicated as a contributing factor in hepatocellular carcinoma. Following absorption, MCLR is taken up via a hepatocyte-specific bile acid carrier. Inside hepatocytes, MCLR selectively binds to protein phosphatases 1 and 2A, resulting in rapid, massive liver damage. However, the apoptotic nature of this toxicosis in rats has not been fully characterized as such at appropriate time points utilizing light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and electrophoresis of hepatic DNA. Rats were administered intraperitoneal saline or MCLR at 500 microg/kg (0.5 micromol/kg) and necropsied at 3 or 9 hours. Light microscopy at 3 hours revealed massive, widespread apoptotic necrosis of the majority of hepatocytes. Hepatocytes were rounded and disassociated, with cell shrinkage, increased eosinophilia, and margination of nuclear chromatin or pyknosis. The apoptotic index increased from 0.03% +/- 0.02% in controls to 205% +/- 12% in MCLR-treated animals (p < or = 0.0001). At 3 hours, transmission electron microscopy revealed hepatocellular changes typical of apoptotic necrosis: rounding and disassociation of hepatocytes, loss of microvilli, and margination and condensation of nuclear chromatin. Laddering of hepatic DNA by electrophoresis and widespread TUNEL staining of hepatocytes were consistent with apoptosis. These results demonstrate that in rats, hepatic damage caused by MCLR is due to extremely rapid induction and progression of apoptosis in virtually every hepatocyte in the liver. This model of fulminant hepatic necrosis should be useful for increased characterization and understanding of the relationship between protein phosphatase inhibition and apoptosis.

Alanine Transaminase↗
PubMedDate not supplied

Effects of acute and subchronic exposure of topically applied fullerene extracts on the mouse skin.

The recent discovery that fullerenes (C60) can be produced in macroscopic quantities has sparked much interest in the chemistry of this unusual molecule. Concerns have also arisen about the potential carcinogenic effects of this molecule. We have addressed the potential acute and subchronic toxic effects of fullerenes applied in benzene on the mouse skin. The acute toxic effects measured in this study included epidermal DNA synthesis and the induction of ornithine decarboxylase activity in the epidermis. At the topical dose of fullerenes used in these studies (i.e., 200 micrograms), we found no effect on either DNA synthesis or ornithine decarboxylase activity over a 72 hour time course after treatment. The subchronic effects of the fullerenes as a mouse skin tumor promoter was assessed by repeatedly applying the chemical to the skin after initiation with the polycyclic aromatic hydrocarbon, 7,12-dimethylbenzanthracene (DMBA). Repeated administration of the fullerenes for up to 24 weeks post-initiation did not result in either benign or malignant skin tumor formation, whereas promotion with the phorbol ester, 12-O-tetradecanoyl-phorbol- 13-acetate (TPA) resulted in the formation of benign skin tumors. Our data indicate that fullerenes applied in benzene at a likely industrial exposure level do not cause acute toxic effects on the mouse skin epidermis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Toxicity of intraperitoneal doses of microcystin-LR in two strains of male mice.

Male Balb/C and Swiss Webster (SW) mice were administered various i.p. doses of microcystin-LR (MCLR) to establish dose-response curves and to determine if a sublethal dose of MCLR would protect against an approximate LD100 min given 2 or 3 days later. Micocystin-LR has an extremely steep dose-lethal response curve in BC mice--LD50 = 32.5 micrograms (micrograms)/kg, approximate LD0 max = 25 micrograms/kg and approximate LD100 min = 40 micrograms/kg. Liver weights increased 64% (BC) and 51% (SW) and kidney weights increased 32% (BC) and 20% (SW) within 200 minutes following administration of an approximate LD100 min of MCLR in naive mice. Grossly and histologically the marked increase in liver weight appeared to be caused primarily from intrahepatic hemorrhage and death is probably a result of hemorrhagic shock. Twenty-four hours following administration of a sublethal dose of MCLR to naive BC mice, liver weights were increased significantly (8.7%), but no clinical signs or histologic lesions were observed. In SW mice, administration of a LD23 of MCLR resulted in significantly increased survivability and survival times when an approximate LD100 min of MCLR was given 3 days later. Survivors of the LD23/LD100 min regimen had 96 hour postdosing liver weights not significantly different from those of mice which died acutely after the same hepatotoxin treatments. These survivors showed weakness, recumbency, anorexia, and icterus, and had marked gross liver lesions. Histologically these lesions were undergoing rapid reparative processes.

Animals↗