Acute hepatitis results from oxidative stress triggered by hepatotoxic drugs causing liver injury and the activation of caspases cascade. The glutathione antioxidant system protects against reactive oxygen species and mitigates development of these processes. The effectiveness of silymarin, a polyphenolic flavonoid, essenthiale, composed of phosphatidyl choline, and melaxen, a melatonin-correcting drug, as hepatoprotectors has been investigated. The variation of 6-sulfatoxymelatonin (aMT6s), resulting from the biotransformation of melatonin, and GSH has been measured. The activities of caspase-1 and caspase-3, glutathione antioxidant system, and NADPH-generating enzymes were determined. The aMT6s decreases in patients with drug hepatitis and recovers with administration of mexalen. GSH increased in the presence of the studied hepatoprotectors. Pathologically activated caspase-1 and caspase-3 decreased their activities in the presence of hepatoprotectors with melaxen showing the highest effect. The positive effect of melatonin appears to be related to the suppression of decompensation of the glutathione antioxidant system functions, recovery of liver redox status, and the attenuation of inhibition of the NADPH supply.

The antiradical activity (ARA) of cinnamic acid derivatives and their structural analogs was evaluated by the ability to inhibit chemiluminescence in a system generating free radicals. The results showed that the ARA of the studied compounds is characterized by the same features as those established previously for the antioxidant activity of these compounds.

Melatonin administered to intact animals increased glutathione concentration and activities of glutathione peroxidase, glutathione reductase, NADP-isocitrate dehydrogenase, and glucose-6-phosphate dehydrogenase in the liver. In animals with toxic hepatitis melatonin treatment decreased glutathione concentration and enzyme activities, which was probably associated with inhibition of free radical oxidation under the influence of this hormone.

Ïðè ñàõàðíîì äèàáåòå 2 òèïà, îñëîaeíåííîì ñòåàòîãåïàòèòîì, íàáëþäàëîñü ïàäåíèå àêòèâíîñòè àêîíèòàòãèäðàòàçû, óâåëè÷åíèå ñîäåðaeàíèÿ äèåíîâûõ êîíúþãàòîâ, óìåíü-øåíèå êîíöåíòðàöèè a-òîêîôåðîëà è èçìåíåíèå óðîâíÿ öèòðàòà â ñûâîðîòêå êðîâè áîëüíûõ, ÷òî ñâèäåòåëüñòâóåò î ðàçâèòèè îêèñëèòåëüíîãî ñòðåññà â ðåçóëüòàòå âîçðàñ-òàíèÿ èíòåíñèâíîñòè ñâîáîäíîðàäèêàëüíîãî îêèñëåíèÿ áèîñóáñòðàòîâ è ñíèaeåíèè ñòåïåíè àíòèîêñèäàíòíîé çàùèòû îðãàíèçìà. Êîìáèíèðîâàííàÿ òåðàïèÿ ñ ìåëàêñåíîì ïðèâîäèëà ê áîëåå çíà÷èòåëüíîìó, â ñðåäíåì íà 36 % (ð £ 0,05), ïî ñðàâíåíèþ ñ áàçèñ-íûì ëå÷åíèåì, èçìåíåíèþ èññëåäóåìûõ ïîêàçàòåëåé â íàïðàâëåíèè íîðìû, ÷òî, ïî-âèäèìîìó, ñâÿçàíî ñ ðåàëèçàöèåé àíòèîêñèäàíòíîãî ýôôåêòà ìåëàòîíèíà.Êëþ÷åâûå ñëîâà: ñàõàðíûé äèàáåò 2 òèïà; íåàëêîãîëüíûé ñòåàòîãåïàòèò; ìåëàêñåí; äèåíîâûå êîíúþãàòû; àêîíèòàòãèäðàòàçà; öèòðàò; a-òîêîôåðîë. ÂÂÅÄÅÍÈÅÏî ñâîåé õèìè÷åñêîé ñòðóêòóðå ìåëàòîíèí (N-àöå-òèë-5-ìåòîêñèòðèïòàìèí) ïðåäñòàâëÿåò ñîáîé ïðîèç-âîäíîå ñåðîòîíèíà -áèîãåííîãî àìèíà, êîòîðûé, â ñâîþ î÷åðåäü, ñèíòåçèðóåòñÿ èç àìèíîêèñëîòû òðèï-òîôàíà. Ìåëàòîíèí ó÷àñòâóåò â ôîðìèðîâàíèè ñóòî÷-íûõ áèîðèòìîâ, òîðìîaeåíèè íåêîòîðûõ ôóíêöèé ãè-ïîôèçà, ðåãóëÿöèè èììóííûõ ðåàêöèé [6]. Äàííûé ãîðìîí ñïîñîáåí òàêaeå äåçàêòèâèðîâàòü àêòèâíûå ôîðìû êèñëîðîäà (ÀÔÊ). Ðàíåå íàìè áûëè ïîëó÷åíû äàííûå î òîì, ÷òî ïðè ââåäåíèè ýêçîãåííîãî ìåëàòîíè-íà ïðîèñõîäèò òîðìîaeåíèå ñâîáîäíîðàäèêàëüíîãî îêèñëåíèÿ (ÑÎ) ó êðûñ ñ òîêñè÷åñêèì ãåïàòèòîì [12], ñàõàðíûì äèàáåòîì [1], ãèïåðòèðåîçîì [4].Ïðåäïîëàãàþò, ÷òî íåçàâèñèìî îò ýòèîëîãè÷åñêèõ ôàêòîðîâ â îñíîâå ðàçâèòèÿ âîñïàëèòåëüíî-íåêðîòè-÷åñêèõ èçìåíåíèé â ïå÷åíè ëåaeàò óíèâåðñàëüíûå ìå-õàíèçìû. Ïðè ñàõàðíîì äèàáåòå â ïå÷åíè ïîâûøàåòñÿ ñîäåðaeàíèå ãëþêîçî-6-ôîñôàòàçû, â ñâÿçè ñ ÷åì îáëåã-÷àåòñÿ âûäåëåíèå ãëþêîçû â êðîâü [7]. Èçáûòî÷íîå ïî-ñòóïëåíèå ñâîáîäíûõ aeèðíûõ êèñëîò â ïå÷åíü, îáðà-çîâàíèå èç íèõ òðèãëèöåðèäîâ, ñíèaeåíèå ñêîðîñòè b-îêèñëåíèÿ ñâîáîäíûõ aeèðíûõ êèñëîò, à òàêaeå ñåê-ðåöèÿ ëèïèäîâ â êðîâîòîê ñïîñîáñòâóþò ôîðìèðîâà-íèþ aeèðîâîé äèñòðîôèè ãåïàòîöèòîâ. Ïðè íåàëêî-ãîëüíîì ñòåàòîãåïàòèòå (ÍÀÑÃ) íàáëþäàåòñÿ ïîâû-øåííàÿ àêòèâíîñòü öèòîõðîìà Ð450 2Å1 â ïå÷åíè, ÷òî ÷àñòî ñîïðîâîaeäàåòñÿ îáðàçîâàíèåì àêòèâíûõ ìåòàáî-ëèòîâ, âêëþ÷àÿ ÀÔÊ. Ïðè ýòîì ïðîäóêòû ïåðåêèñíîãî îêèñëåíèÿ ëèïèäîâ (ÏÎË) âûçûâàþò íàáóõàíèå ìèòî-õîíäðèé, ëîìêîñòü ìåìáðàí ëèçîñîì, íàðóøåíèå öåëî-ñòíîñòè êëåòî÷íûõ ìåìáðàí [17].Ê âàaeíåéøèì íåôåðìåíòàòèâíûì àíòèîêñèäàíòàì îòíîñèòñÿ âèòàìèí Å, êîòîðûé çàùèùàåò âíóòðåííèå ìèòîõîíäðèàëüíûå ìåìáðàíû, à òàêaeå ëèçîìû îò ïî-âðåaeäàþùåãî äåéñòâèÿ ïåðåêèñåé, ïîääåðaeèâàåò ôóíêöèîíàëüíóþ öåëîñòíîñòü âíåøíåé öèòîïëàçìàòè-÷åñêîé ìåìáðàíû êëåòîê [15]. a-Òîêîôåðîë ýôôåêòèâ-íî ïðåðûâàåò öåïíûå ñâîáîäíîðàäèêàëüíûå ðåàêöèè â ïðîöåññå ïåðåîêèñëåíèÿ íåíàñûùåííûõ aeèðíûõ êè-ñëîò â ìåìáðàíàõ, ïðåäóïðåaeäàåò àòåðîãåííûå èçìå-íåíèÿ ëèïîïðîòåèíîâ íèçêîé ïëîòíîñòè. Ñóùåñòâóåò ïðÿìàÿ ñâÿçü ìåaeäó óðîâíåì âèòàìèíà Å è èíòåíñèâ-íîñòüþ òêàíåâîãî äûõàíèÿ è îáðàòíàÿ ñâÿçü ñî ñòåïå-íüþ îêèñëåíèÿ ëèïèäîâ [15].Âàaeíåéøåå ìåñòî â íåôåðìåíòàòèâíîì çâåíå àíòè-îêñèäàíòíîé ñèñòåìû (ÀÎÑ) çàíèìàåò öèòðàò, êîòî-ðûé îòíîñè...

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Effect of the proliferative regulators chalone and antichalone on the free radical system is studied on isolated and perfused rat liver under normal conditions and after ammonium chloride load (5 mM). It is shown that chalone suppressed both lipid peroxidation and antiradical system, while antichalone exhibits opposite effects on these processes. Ammonium chloride abolishes the effect of antichalone and does not change the effect produced by chalone. A hypothesis is proposed that specific function of the organ predominates over its response to local regulatory stimuli.Key Words: chalone; antichalone; isolated liver; lipid peroxidation; antiradical activityThe majority of studies in the field of regulation of cell homeostasis are aimed at investigating final effects of regulatory factors and usually employ morphological methods. Such an approach ignores cell processes which occur after the regulatory stimulus reaches the cell to the appearance of morphological changes triggered by this signal. These processes occurring during the lag-period prepare the target cell to competent response to the action of growth factors. MATERIALS AND METHODSIsolated livers from random-bred albino rats of both sexes (221+3 g) were used in the experiments. The animals were sacrificed in the morning after 24-h fasting. The liver of ketamine-narcotized and heparinized rat was connected via v.portae to a perfusion system as descnSed previously [2]. Then it was isolated from ligaments, removed from the abdominal cavity, and placed into a thermoeontrolled perfusion chamber. At the first stage the liver was perfused for 30 rain with Hank's medium (37~ pH 7.45, 5 ml/min) for stabilization of metabolic processes. During the next 30 rain the liver was perfused under the same conditions with experimental solutions containing ehalone, antiDepartment of Medical Biology and Genetics, N. N. Burdenko State Medical Academy, Voronezh chalone, 5 mM NH~C1, or a combination of growth factor with NH4CI. The preparations were added in a proportion of one dose per 10 ml. The dose was calculated on the basis of the antioxidant properties of chalone and antichalone discovered by A. N. Pashkov [4]. The amount of preparation inducing 50% quenching of chemiluminescence was taken as one dose.After the end of perfusion, the liver was frozen in liquid nitrogen and then homogenized in physiological saline containing Triton X-100 and centrifuged for 10 min at 15.000 g min. The contents of protein (by the method of Lowry) and malonic dialdehyde (MDA) [7] in the supernatant were measured. Antiradical activity of the supernatant was evaluated by chemiluminescence quenching on an KhLMITs-01 chemiluminometer [3].The significance of differences was evaluated by one-factor dispersion analysis. RESULTSOur results show that cell proliferation regulators specifically modulate such phylogenetically old protess as lipid peroxidation (LPO).As seen from Fig. 1, ehalone and antichalone had opposite effects on the intensity of LPO, judging from the content of MDA in isolated liver. ...

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