Журнал "Макрогетероциклы"

Natalya A. Antonova,^a Viktoria P. Osipova,^b Margarita N. Kolyada,^b Natalya  O. Movchan,^b Elena R. Milaeva,^c@ and Yuriy T. Pimenov^a

^аAstrakhan State Technical University, 414025 Astrakhan, Russia

^bSouthern Scientific Centre RAS, 344006 Rostov-on-Don, Russia

^cM.V. Lomonosov Moscow State University, Chemistry Department, 119991 Moscow, Russia

^@Corresponding author E-mail: milaeva@org.chem.msu.su

DOI: 10.6060/mhc2010.2-3.139

The synthetic analogues of natural porphyrins are widely used in medicine as pharmaceutical diagnostic markers. It was shown the possibility of applying porphyrins in the therapy of the diseases, connected with the development of oxidative stress. The paper presents the results of the study of antioxidant activity of the free base meso-tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin R₄PH₂, as well as non-substituted analogue - meso-tetraphenylporphyrin (TPPH₂) in the conditions of autooxidation and under promotion of oxidation by organotin compounds. The ability of the free base of porphyrin containing antioxidant 2,6-di-tert-butyl phenolic groups to decrease the oxidation by peroxide of lipids liver gomogenates, sturgeon sperm, fish feed has been studied.  Accumulation of intermediate oxidation products from liver homogenates, sperm of the Russian sturgeon (Acipenser guldenstadti Brandt) as a stable complex with thiobarbituric acid (TBARS) and oxidation products from fish feed (hydroperoxides ROOH) was monitored by spectrophotometry and iodometric titration, respectively. The efficiency of antioxidative action (EAA) of studed porphyrins in each series of experiences with varying duration of lipids peroxidation in liver homogenates was calculated as EAA = [(C0-C1)/C0]·100%, where C1 is TBARS concentration in homogenates of liver containing the studied compounds and C0 in a control experiment without additions. If the value of EAA factor was positive, it was considered that the testing material shows the antioxidative action; in the case of negative EAD factor it was considered that the testing material shows the prooxidative activity. The initial concentration of the studied compounds was 0,1 mM. In the model system the antioxidant activity of R₄PH₂ in peroxidation of liver lipids remains almost constant in the wide interval of concentrations (0,01 -  10 mM). It was established that in the middle stages of the oxidation process (3 h, 24 h) the antioxidant action of TPPH2 is inverted to the prooxidant. The presence of 2,6-di-tert-butylphenolic groups in the free base porphyrin macrocycle results in an inhibitory effect. The introduction of the redox-active ion metal in the macrocycle reduces the inhibition effect of 2,6-di-tert-butylphenol fragments in oxidative destruction of liver lipids. The prooxidantive properties of TPPH2 during the oxidive destruction of the lipids of fish fodder were observed. Addition of this porphyrin to lipid drawing from the fish fodder in the concentration 150 mg/kg of fodder leads to an increase in the level the formation of primary oxidation products, namely, hydroperoxides ROOH. The organic derivatives of tin, acting as superecotoxicants, promote peroxidation of lipids in the drawing from the fish fodder. The greatest promoting effect of the lipid peroxidation was observed in the presence of СН₃SnCl₃. It was shown earlier that toxicity of heavy metals compounds could be connected with complexation of important bio dartboards as well as development of radical processes. So it is possible to use the active radicals traps as antidotes. With the aim of increasing of toxicoprotector efficiency, we offer to use compounds containing antioxidation part and complexating groups in molecule. Such compounds can be porphyrinic systems, but it is necessary to take into account the possibility of revealing of prooxidative properties by these compounds. It is discovered, that TPPH₂ strengthens the promoting influence of the methyl derivatives of tin on the level of accumulation of hydroperoxides in the lipid drawing from the fish fodder. Since the oxidative activity of TPPH2 and RnSnCl_4-n are summed consequently the application of TPPH₂ for detoxication of RnSnCl_4-n is inadvisable. The promoting activity of organotin species in the presence of the porphyrin containing sterically-hindered phenolic moieties decreases significantly when compared with the activity of organotins alone. R4PH2 was superior to the standard antioxidants α-tocopherol, 2,6-di(tert-butyl)phenols, 2,6-di(tert-butyl)-4-methylphenol (ionol).

Keywords: Porphyrins, metal porphyrins, peroxide oxidation, liver, fish sperm, fish fodder, organotin compounds.

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