Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to investigate the effects of single and repeated administration of CP-55,940 [(-)-cis-3-[2-hydroxy-4-(1, 1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol)] on behaviour, energy metabolism and biotransformation. Single intraperitoneal administration to male Sprague-Dawley rats of CP-55,940 (0.4 mg/kg), induced a behavioural response characterized by 'splayed hind limbs', antinociception, hypothermia and a decrease in locomotor activity. Brain and liver mitochondria of the CP-55,940-treated rats exhibited an increase in respiration and no changes in ADP/O and citrate synthase specific activity. Repeated intraperitoneal administration of CP-55,940 (0.4 mg/kg, 11 days) induced behavioural tolerance, disappearance of the increase in the mitochondrial oxygen consumption as well as an increase in the monooxygenase activities and the content of liver microsomal cytochrome P450. Some hepatic metabolizing enzymes of the cytosolic glutathione-centre system were also affected. Previous studies had indicated that the tolerance after chronic administration of CP-55,940 could be due to down-regulation of brain cannabinoid receptors. The present findings demonstrate that the behavioural tolerance occurs together with modified biotransformation activities.
 ...
PMID:Chronic cannabinoid, CP-55,940, administration alters biotransformation in the rat. 890 24

Juveniles of Solea solea were sampled during the spring season in three consecutive years at a marine site by the mouth of the Ebre river. The aim was to assess if the extractive works from the toxic load upstream the river could be reflected on the health status of the fish living at the immediate sea. The biomarkers selected for the in vivo field study are commonly used as indicators of chemical exposures. They include activities of energy metabolism: lactate dehydrogenase (LDH) and citrate synthase (CS); neurotoxicity: cholinesterases (ChE); xenobiotic metabolism: cytochrome P450 (CYP)-dependent: EROD and BFCOD, carboxylesterase (CbE), glutathione S-transferase (GST) and uridine diphosphate glucuronyltransferase (UDPGT); and oxidative stress parameters such as catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX) as well as levels of lipid peroxidation (LPO). These biomarkers were mostly analysed in liver but also in gills and muscle depending on their particular tissue distribution and role. A complementary in vitro approach was also sought to see the capacity of common emerging contaminants (pharmaceuticals and personal care products; PPCPs) to interact with the liver microsomal detoxification system of the fish (EROD, BFCOD and CbE activities). The results indicated that in fish sampled in 2015 there was an enhancement in detoxification parameters (EROD, BFCOD and gill GR), muscular ChEs and gill CS, but a decrease in CbE activity and a marked oxidative stress situation (increased LPO and decreased CAT activity). Also, 4 out of the 10 PPCPs tested in vitro were able to interact with the CYP3A4 (BFCOD) enzymatic system while the lipid regulators simvastatin and fenofibrate inhibited CbE activity, as it occurs in higher vertebrates. The in vivo results support the use of a multibiomarker approach when assessing the disturbances due to chemical exposures, not only spatially but also over time, once the influence of other variables has been taken into consideration. The in vitro results highlight the importance of the CYP3A4 and CbE pathway in pharmaceutical metabolism, also in fish.
...
PMID:The use of juvenile Solea solea as sentinel in the marine platform of the Ebre Delta: in vitro interaction of emerging contaminants with the liver detoxification system. 2735 7

Specimens of two endemic cyprinids, Squalius laietanus (Catalan chub) and Barbus meridionalis (Mediterranean barbel), were sampled from a reference site in a small stream of the Ripoll River (NW Mediterranean) outside of their reproductive season. Biomarkers involved in xenobiotic-mediated responses were individually contrasted in fish of both species and 17 perfluoroalkyl substances (PFASs) analysed in muscle to reveal bioaccumulation trends. The parameters were in muscle: cholinesterases, metabolic lactate dehydrogenase (LDH) and citrate synthase (CS); and in liver: cytochrome P450 dependent activities (EROD and BFCOD), carboxylesterase (CE), glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPX) and catalase (CAT). All markers are considered adaptive defence mechanism to face stress. Sensitivity to a model pesticide: dichlorvos was also contrasted in vitro in muscular acetylcholinesterase (AChE) and hepatic CE to reveal species sensitivity to neurotoxic chemicals. Enzymatic activities related to protective mechanisms such as butyrylcholinesterase (BuChE), CE and CAT were higher in chub whereas the antioxidant defences GR and GPX were higher in barbel. Aerobic CS was also higher in barbel while anaerobic LDH was so in chub. EROD activity did not differ between the two species but BFCOD activity was higher in barbel. Levels of PFAS were higher in barbel likely due to its benthic habitat. The in vitro tests revealed higher sensitivity to dichlorvos of muscular AChE in chub (lower IC50) which was probably compensated by a higher catalytic efficiency of CE. All these former biochemical particularities are discussed in terms of fish ecological performance in front of anthropogenic stressors.
 ...
PMID:Biochemical aspects of susceptibility to stressors in two small cyprinids Squalius laietanus and Barbus meridionalis from the NW Mediterranean. 3317 Dec 99