Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013911 (emaciation)
 1,059 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male New Zealand White rabbits were treated with microsomal enzyme inducers, inhibitors of hemoprotein synthesis or action, and glutathione precursor and depletor before they were orally given the median lethal dose (LD50) of aflatoxin B1 (AFB1; 0.4 mg/kg) at the start of a 7-day experimental period. The drugs administered, mean duration of illness (hours), and survival percentage were as follows: controls (saline solution)-85, 50%; phenobarbital (PB)-100, 100%; phenylbutazone-115, 67%; benzoflavone-39, 17%; stanozolol-67, 67%; cobaltous chloride (CoCl2)-46, 67%; piperonyl butoxide (PBO)-88, 100% cysteine (CYS)-68, 100%; ethyl maleate-71, 83%. Signs of toxicosis included decreased feed and water consumption, weight loss, dehydration, lethargy, and emaciation; some rabbits died or were euthanatized. Clinico-pathologic changes included increased serum aspartate aminotransferase (AST) activity by 24 hours and bilirubin concentration by 48 to 72 hours after AFB1 was given. Grossly, livers were pale or tan and friable, with prominent lobular architecture. Kidneys of affected rabbits were pale to dark red. Microscopically, livers were normal or had lesions as great as extensive necrosis, hemorrhage, mineralization, and bile duct proliferation. Treatment of rabbits with PB, CoCl2, PBO, and CYS protected against AFB1 hepatic pathology, and PB, PBO, and CYS also had protective effect against lethality. Ethyl maleate provided some protection against lethality and increased serum AST activity and bilirubin concentration. Toxicosis was enhanced by benzoflavone; phenylbutazone and stanozolol had litte influence.
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PMID:Effect of enzyme inducers and inhibitors and glutathione precursor and depleter on induced acute aflatoxicosis in rabbits. 680 67

Previous repeated inhalation exposure studies revealed two independent organotropic effects of inhaled propineb dust: One was restricted to the lung, the other to muscle weakness of hindlimbs. These effects were believed to be causally related to the principle decomposition products of this type of dithiocarbamate in the biological milieu and related to zinc and carbon disulfide. Two mechanistic 1-wk inhalation studies were performed, each focusing on one of these findings. The 7 x 6-h/day repeated-exposure inhalation study analyzed whether the nature of the response occurring at the alveolar level is "adaptive" or "early adverse" and whether soluble zinc is the causative agent. Groups of 18 female rats were exposed nose-only to mean concentrations of 0, 1.1, 5.5, and 25.8 mg propineb/m(3) and 6.9 mg ZnO/m(3). On postexposure days 1, 3, and 15 the time course of responses was analyzed by bronchoalveolar lavage (BAL), including quantification of Zn and metallothionein (MT) in BAL cells. Clinical evidence of muscular weakness was investigated separately in 20 female Wistar rats exposed to 70 mg propineb/m(3) on 5 consecutive days (6 h/day), followed by a 2-wk postexposure period. Clinical signs, body weights, and feed and water consumption were recorded as frequently as technically feasible. Fifty percent of rats received an oral cysteine supplementation to verify/refute the hypothesis that the incapacitation observed in previous studies is the cause of emaciation and associated impairment of CS(2) detoxification. The findings of the first study are consistent with this hypothesis, namely, that soluble Zn triggers a series of pulmonary events that is consistent with the homeostasis of this essential metal. It is concluded, accordingly, that the adjusted maximal workplace level for ZnO is also valid for propineb to preclude Zn-mediated responses to occur in the lung. With respect to muscular effects, this mechanistic study demonstrates further that the increased detoxification capacity afforded by oral supplementation of cysteine mitigates markedly the toxic potency of propineb. Procedural variables specific to the inhalation bioassay appear to be decisive for the elicitation of muscular effects. The major variable is considered to be the large drop in body weights associated with each exposure session and the concomitantly decreased uptake of essential nutritional factors (e.g., cysteine) involved in the detoxification of this compound. Accordingly, the muscular deficits elicited by high concentrations of propineb are viewed to be secondary effects in an animal species likely to be more susceptible to this type of change than humans (Pauluhn & Rosenbruch, 2003).
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PMID:Inhalation toxicity of propineb. Part II: Results of mechanistic studies in rats. 1268 57