Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we investigated the in vitro effects of arginine, N-acetylarginine, argininic acid and homoarginine on some oxidative stress parameters in rat brain in the hope to identify a possible mechanism for the brain damage in hyperargininemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the cerebral cortex of rats in the presence of various concentrations of these compounds. The results showed that all guanidino compounds tested significantly increased chemiluminescence and decreased TRAP at concentrations similar to those observed in the tissue of hyperargininemic patients. Furthermore, these compounds inhibited CAT and GSH-Px activities to varying extents, with GSH-Px activity being more susceptible to their action. In turn, argininic acid inhibited all enzyme activities, and its main action was also directed towards GSH-Px. The results suggest that oxidative stress caused by guanidino compounds may be involved in the brain dysfunction amongst other potential pathophysiological mechanisms observed in hyperargininemia.
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PMID:In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia. 1174 72

Pharmaceuticals are continuously dispersed into the environment, as a result of human and veterinary use, and have become a relevant environmental concern. In the present study, the acute toxicity of three therapeutic agents (diazepam, clofibrate, and clofibric acid) and a detergent, sodium dodecylsulphate (SDS), to the euryhaline fish Gambusia holbrooki was evaluated. Special attention was devoted to oxidative stress parameters. G. holbrooki males, captured in the estuary of the Minho River (NW Portugal), were exposed for 96 h to the selected compounds. The following oxidative stress biomarkers were evaluated in gills and liver tissues: reduced and oxidised glutathione, lipid peroxidation, and several antioxidant enzymes, namely (1) total and selenium-dependent glutathione peroxidase (GPx), (2) glutathione reductase (GRed), (3) copper-zinc superoxide dismutase (Cu-ZnSOD) and manganese superoxide dismutase (MnSOD), and (4) glutathione-S-transferases (GSTs). In the particular case of diazepam, swimming behaviour was also evaluated. The obtained results indicate an overall diminished oxidative stress response caused by SDS and diazepam. Oxidative-based alterations were observed after exposure to clofibrate and clofibric acid, with modifications of several enzymatic activities. Diazepam caused evident behavioural changes: animals showed dark pigmentation and also abnormal postures, namely lethargy and anomalous movement.
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PMID:Behaviour and biomarkers of oxidative stress in Gambusia holbrooki after acute exposure to widely used pharmaceuticals and a detergent. 1824 7

A time course experimental challenge of WSSV was carried out to examine the clearance of WSSV in Macrobrachium rosenbergii and the consequent immunological changes. The experimental animals were injected with WSSV and the samples of gills, pleopods, head soft tissue and hemolymph were collected at different intervals of 1, 3, 5, 10, 25, 50, 75 and 100 days post infection (p.i.). WSSV infection and clearing were confirmed by single step PCR, nested PCR and bioassay. At 3 days p.i., M. rosenbergii became lethargic and stopped feeding in contrast to the control prawns that behaved and fed normally. However, the WSSV-injected prawns suffered no mortality during the experimental period and recovered without any further gross signs of disease or any mortality over a period of 100 days p.i. The single step PCR analysis showed positive at 1, 3 and 5 days p.i. in gills, head soft tissue, pleopods and hemolymph, and all the organs showed negative at 10 days p.i. onwards. The nested PCR results showed that all organs were positive for WSSV from 3 days p.i. and extended up to 25 days p.i. At 50 days p.i, head soft tissue sample alone showed WSSV-positive while all other organs were negative by nested PCR. All the organs at 75 and 100 days p.i. showed nested PCR negative for WSSV as observed in the control prawn. The hemolymph collected from experimentally infected M. rosenbergii at 1, 3 and 5 days p.i. caused 100% mortality at 40 h p.i., 55 h p.i. and 72 h p.i, respectively in Penaeus monodon whereas hemolymph collected at 10, 25, 50, 75 and 100 days p.i. failed to cause mortality in shrimp. The moribund shrimp showed WSSV-positive and surviving shrimp showed negative by PCR. Immunological parameters such as proPO, O(2)(-) and clotting time in WSSV-injected M. rosenbergii were found to be significantly higher than those of the control groups, whereas THC and superoxide dismutase were significantly lower when compared to control groups.
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PMID:Clearance of white spot syndrome virus (WSSV) and immunological changes in experimentally WSSV-injected Macrobrachium rosenbergii. 1860 47

Cases of pet poisoning and infant renal calculus have attracted much attention to the toxicity of melamine and its derivatives, such as cyanuric acid. Although individually melamine and cyanuric acid have low toxicity, their simultaneous presence can cause severe damage. Little is known about their adverse effects on the reproductive system. In this study, mice were orally administrated 1, 5 or 25 mg/kg/d of both melamine and cyanuric acid for 13 weeks. Lethargy, rough hair, and reduction of food and water intake and of body and testis weight were found after exposure to the combination, and pathological changes were found in the morphology of the testes, such as disruption of the seminiferous tubule structure, decrease of the spermatogenic cell series and coagulation necrosis. Total antioxidant capacity and superoxide dismutase activities and glutathione concentration was lower and malondialdehyde concentration was higher than in control mice. The activities of malate dehydrogenase, lactate dehydrogenase and Na(+)/K(+)-ATPase were also lower in combination treated mice than in control mice. These results indicate that the combined exposure to both melamine and cyanuric acid damaged testes in mice by either a direct or indirect effect, which may be related to renal failure and secondary anorexia. Oxidative stress and lower energy production levels both contributed to the testicular damage.
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PMID:Effect on morphology, oxidative stress and energy metabolism enzymes in the testes of mice after a 13-week oral administration of melamine and cyanuric acid combination. 2322 May 42

Food and feeds contaminated with mycotoxins have been a threat to the rearing industry by causing some of the most fatal toxic reactions not only in the farm animals but also in humans who consume them. Toxicity to juvenile goats was induced by feed contamination with T-2 toxin (at 10 and 20 ppm dosage; group I and II, respectively). The toxicity impact was assessed on days 15 and 30 post treatment with respect to growth performance, oxidative stress, apoptotic studies and detailed pathomorphology. The study revealed that apart from the obvious clinical toxicosis (weakness, lethargy, and retardation in growth), the toxin fed groups also exhibited significant haematological (reduced hemoglobin, total leukocyte and thrombocyte counts) and biochemical changes (increased levels of oxidative stress markers with concomitant decrease in levels of serum and tissue catalase and superoxide dismutase). The pathomorphological and histological alterations suggested that the liver and intestine were the most affected organs. Ultra-structurally, varying degrees of degeneration, cytoplasmic vacuolations and pleomorphic mitochondria were observed in the hepatocytes and the enterocytes of the intestine. Kidney also revealed extensive degeneration of the cytoplasmic organelles with similar condensation of the heterochromatin whereas the neuronal degeneration was characterized by circular, whirling structures. In addition, the central vein and portal triad of the hepatocytes, cryptic epithelial cells of the intestine, MLNs in the lymphoid follicles, PCT and DCT of the nephronal tissues and the white pulp of the spleen exhibited extensive apoptosis. In this study, it was also observed that the expression of HSPs, pro-apoptotic proteins and pro-inflammatory cytokines were significantly upregulated in response to the toxin treatment. These results suggest that the pathogenesis of T-2 toxicosis in goats employs oxidative, apoptotic and inflammatory mechanisms.
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PMID:Toxicopathological studies on the effects of T-2 mycotoxin and their interaction in juvenile goats. 3221 55