ABSTRACT
The bioantioxidant activity of the synthesized by us on the base of the diatomic phenol compound--3,5-di-t-butylpyrocatechol--has been studied. It was shown that this substance exhibits more pronounced antioxidant properties than tocopherol on the lipid peroxidation process in the rat brain homogenate appears in concentrations right up to 10(-8)-10(-7) M. Antioxidant effect of 3,5-di-t-butylpyrocatechol protecting action correlation has been found in the simulation of such pathological organism states as hypoxia, inflammation, burn, pain. All above mentioned results confirms the expedience of search for new drugs based on diatomic phenols.
Subject(s)
Antioxidants/pharmacology , Burns/drug therapy , Cyclohexanes/pharmacology , Hypoxia/drug therapy , Inflammation/drug therapy , Pain/drug therapy , Animals , Brain/drug effects , Brain/metabolism , Burns/metabolism , Butylated Hydroxytoluene/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Hypoxia/metabolism , Inflammation/metabolism , Injections, Intraperitoneal , Lipid Peroxidation/drug effects , Male , Mice , Pain/metabolism , Rats , Treatment Outcome , Vitamin E/pharmacologyABSTRACT
Swelling of C6 glioma cells in hypotonic medium (180 mOsm) results in two- to three-fold activation of K+ (86Rb+) influx suppressed by 10 microM bumetanide. Bumetanide-sensitive transport of 86Rb+ is dependent on extracellular K+, Na+ and Cl- both in iso-osmotic conditions and under hypo-osmotic shock, supporting the notion that it is mediated by Na+,K+,2Cl- cotransport. Inhibitors of protein kinase C (10 microM polymyxin B and l microM staurosporine) had no significant effect on basal cotransport but reduced its hypotonic stimulation by 70-80%. Similar results were obtained with calmodulin antagonist R24571 (10 microM), indicating Ca2+/calmodulin-dependence of the process. Influence of polymyxin B and R24571 was not additive. Swelling-activated Na+,K+,2Cl- cotransport was also suppressed by protein kinase C activator PMA (l microM). By contrast, preincubation of cells with inhibitors of protein phosphatases (100 microM vanadate, 5 mM fluoride and 0.5 microM okadaic acid) activated greatly the bumetanide-sensitive 86Rb+ uptake in isotonic conditions, while a subsequent hypotonic swelling led to smaller or no increment. These results indicate the involvement of Ca2+/calmodulin-dependent staurosporine/polymyxin B-sensitive protein kinase other than protein kinase C in swelling-induced activation of Na+,K+,2Cl- cotransport in glial cells.
Subject(s)
Carrier Proteins/metabolism , Cell Size , Bumetanide/pharmacology , Chlorides/metabolism , Chlorides/pharmacology , Diuretics/pharmacology , Glioma/metabolism , Hypotonic Solutions/pharmacology , Ion Exchange , Kinetics , Osmolar Concentration , Ouabain/pharmacology , Potassium/metabolism , Potassium/pharmacology , Rubidium/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , Sodium/metabolism , Sodium/pharmacology , Sodium-Potassium-Chloride Symporters , Tumor Cells, CulturedSubject(s)
Astrocytes/cytology , Cell Hypoxia , Animals , Astrocytes/metabolism , Cell Survival , Cells, Cultured , Free Radicals , Oxidation-Reduction , RatsABSTRACT
Amphiphilic membrane-addressed antioxidants differing in their hydrophobic-hydrophilic balance, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate, (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate, and (3,5-di-tert-butyl-2-hydroxyphenyl)-5-cholesten-3 beta-yl phosphate, were synthesized starting from 3,5-di-tert-butyl-o-quinone. Even at 10(-8) M concentration, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate and (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate inhibit formation of malonic aldehyde during peroxidation of lipids from rat brain homogenate initiated with a Fe(2+)-ascorbate system. At 10(-4) M and higher concentrations of antioxidants in the brain homogenate, the formation of malonic aldehyde is inhibited more efficiently than with tocopherol at the same concentrations.
