Chemico-biological interactions
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Chem. Biol. Interact. · Mar 2013
In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.
Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. ⋯ The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones.
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Chem. Biol. Interact. · Mar 2013
Modulation of cholinergic pathways and inflammatory mediators in blast-induced traumatic brain injury.
Cholinergic activity has been recognized as a major regulatory component of stress responses after traumatic brain injury (TBI). Centrally acting acetylcholinesterase (AChE) inhibitors are also being considered as potential therapeutic candidates against TBI mediated cognitive impairments. We have evaluated the expression of molecules involved in cholinergic and inflammatory pathways in various regions of brain after repeated blast exposures in mice. ⋯ Changes in the expression of myeloperoxidase in the cerebellum were confirmed by Western blotting. These results indicate that early pathologic progression of blast TBI involves dysregulation of cholinergic and inflammatory pathways related genes. Acute changes in molecules involved in the modulation of cholinergic and inflammatory pathways after blast TBI can cause long-term central and peripheral pathophysiological changes.
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Chem. Biol. Interact. · May 2012
Inhibition and inactivation of cytochrome P450 2A6 and cytochrome P450 2A13 by menthofuran, β-nicotyrine and menthol.
Nicotine is the primary addictive agent in tobacco products and is metabolized in humans by CYP2A6. Decreased CYP2A6 activity has been associated with decreased smoking. The extrahepatic enzyme, CYP2A13 (94% identical to CYP2A6) also catalyzes the metabolism of nicotine, but is most noted for its role in the metabolic activation of the tobacco specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). ⋯ Menthofuran was an inhibitor of CYPA13 (KI, 1.24 μM). The inactivation of CYP2A6 by either β-nicotyrine or menthofuran was not due to modification of the heme and was likely due to modification of the apo-protein. These studies suggest that β-nicotyrine, but not menthol may influence nicotine and NNK metabolism in smokers.
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Chem. Biol. Interact. · Mar 2012
Prevention of selenite induced oxidative stress and cataractogenesis by luteolin isolated from Vitex negundo.
Free radical mediated oxidative stress plays a crucial role in the pathogenesis of cataract and the present study was to determine the efficacy of luteolin in preventing selenite induced oxidative stress and cataractogenesis in vitro. Luteolin is a bioactive flavonoid, isolated and characterized from the leaves of Vitex negundo. Lenses were extracted from Sprague-Dawley strain rats and were organ cultured in DMEM medium. ⋯ Additionally decreased glutathione level and increased reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were observed. Luteolin treatment abated selenite induced oxidative stress and cataractogenesis by maintaining antioxidant status, reducing ROS generation and lipid peroxidation in the lens. These finding demonstrated the anticataractogenic effect of luteolin by virtue of its antioxidant property, which has been reported in this paper for the first time.
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Chem. Biol. Interact. · Sep 2011
Effect of galangin supplementation on oxidative damage and inflammatory changes in fructose-fed rat liver.
The study examined the effects of galangin (GA) on oxidative stress, inflammatory cytokine levels and nuclear factor-kappa B (NF-κB) activation in fructose-fed rat liver. Adult male albino Wistar rats were divided into 4 groups. Groups 1 and 4 received the control diet containing starch as the source of carbohydrate while groups 2 and 3 were fed a diet containing fructose. ⋯ However, treatment with GA downregulated the expression of these cytokines. Translocation of NF-κB into the nucleus was also increased in fructose diet-fed animals, which was prevented by GA. These results suggest that GA prevents oxidative damage and has a downregulatory effect on the inflammatory pathway in liver of fructose-fed rats.