PubMed Health⌕ Search

Biomedical subjects

E Serbinova

Publications and source records attributed to E Serbinova.

25 records · Page 2Linked to original sources

Toxic and protective effects of antioxidants in biomembranes.

Natural and synthetic antioxidants (AOs) are widely used as stabilizers of biomembranes against lipid peroxidation (LPO). Natural AOs (tocopherols, ubiquinols) containing hydrocarbon "tails" do not disturb the membrane lipid bilayer. Synthetic AOs devoid of hydrocarbon radicals may perturb the lipid bilayer. It was shown that AOs devoid of hydrocarbon tails (butylated hydroxytoluene, 2,2,5,7,8-pentamethyl-6-hydroxychromane) exerted toxic effects on erythrocyte membranes (induced hemolysis), on sarcoplasmic reticulum membranes (inhibited Ca2+-transport) and on platelet membranes (initiated Ca2+-dependent aggregation) in vitro. These AOs are the substrates of cytochrome P-450, and underwent oxidative hydroxylation. This suggests that they have short half-life times in biomembranes and in the organism. Antioxidants with hydrocarbon tails, are hydroxylated at very low rates and are slowly excreted. Antioxidants devoid of hydrocarbon tails, are 10-20 fold more potent LPO inhibitors than the corresponding AOs with hydrocarbon tails. The strategy of AOs application for long and short-term stabilization of biomembranes against LPO in vivo is discussed.

Animals↗

Effect of some heavy metal salts on hepatic monooxygenases after subchronic exposure.

The effects of subchronic exposure of some heavy metal salts on the activity of the rat liver monooxygenases and NADPH-dependent lipid peroxidation have been studied. The salts of Co, Cd and Zn (when given repeatedly for one month in subtoxic doses) shortened the duration of hexobarbital sleeping time, increased the activities of Ethylmorphine-N-demethylase (EMD) and Benzphetamine-N-demethylase (BND), and the cytochrome P-450 and heme contents. The same metal salts increased the activity of delta-aminolevulinic acid synthetase (ALAS), decreased that of Heme-oxygenase and decreased NADPH-dependent lipid peroxidation. Whereas the salts of Co, Cd and Zn seem to exert an enzyme-inducing action on the mixed function oxidizing enzyme systems, the salts of Hg and Ni did not show such effects.

5-Aminolevulinate Synthetase↗

On the mechanism of the enzyme-inducing action of some heavy metal salts.

The effect of Co(NO3)2, CdSO4, NiSO4, ZnSO4, and HgCl2 (given repeatedly in subtoxic doses in the drinking water for 30 days) on rat liver monooxygenases was studied in experiments on male Wistar rats. The salts of Co, Cd, and Zn increased the activity of benzphetamine-N-demethylase, the content of cytochrome P-450 and microsomal heme. The data suggest that these salts exert an enzyme-inducing effect on the hepatic monooxygenases. The same metal salts (Co, Cd, and Zn) increased the activity of delta-aminolevulinic acid (ALA) synthetase and decreased that of heme oxygenase. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein. HgCl2 and NiSO4 did not exert an enzyme-inducing action. The lack of change in the activity of NADPH-cytochrome c reductase and cytochrome b5 (except for ZnSO4) suggests that these components of the electron transport chain are not likely to be involved in the enzyme-inducing action of the heavy metal salts.

5-Aminolevulinate Synthetase↗

Is a relay mechanism of antioxidant effect of tocopherols valuable for membrane systems?

The efficiency of the inhibitory action of 3 tocols derivatives--alpha-tocopherol (alpha-T), 2, 2, 5, 7, 8-pentamethylchromane (PMC) and alpha-tocopherylacetate (alpha-TA) on lipid peroxidation (LPO) in rat liver microsomes was compared. LPO was induced by O2-generating systems (Fe2+ + NADPH, Fe2+ + ascorbate) or by ROO generating system (Fe2+ + tert-butyl hydroperoxide). It was found that PMC was much more potent LPO inhibitor than alpha-T, whereas alpha-TA was ineffective in all LPO-initiating systems used. The protective effect against cytochrome P-450 (cyt. P-450) degradation induced by LPO-products was also maximal for PMC and minimal for alpha-TA. The data obtained suggest that the presence of phytyl radical is not necessary for antioxidant activity of tocols and contradict the hypothesis about a relay mechanism of antioxidant action of tocopherols in biomembranes.

Animals↗

Hepatic mixed-function oxidase system and microsomal lipid peroxidation in rats treated with a synthetic immunomodulator, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP).

Effects of synthetic muramyl dipeptide (MDP) on activity of liver microsomal mixed-function oxidase system and on the susceptibility of liver microsomes to lipid peroxidation, were tested in rats at intervals of 1 or 24 hours after single i.p. injection of MDP (1 mg per animal). No significant changes were found in levels of cytochrome P-450 and b5, microsomal heme, or in activities of aniline hydroxylase, ethylmorphine demethylase, glucuronide transferase or cytosol glutathione-S-transferase. However, significantly less (about 45%) TBA-reactive material accumulated in microsomal samples at the 1 h-interval after the MDP administration. The same inhibitory effect of MDP on lipid peroxidation was shown in vitro (in 1 mM concentration) after incubation of microsomes with the NADPH/ADP/Fe system.

Acetylmuramyl-Alanyl-Isoglutamine↗