Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver

Ланкин, В. З.; Иванова, М. В.; Konovalova, G. G.; Tikhaze, A. K.; Kaminnyi, A. I.; Кухарчук, В. В.

doi:10.1007/s10517-007-0144-5

Cited by 10 publications

(8 citation statements)

References 11 publications

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“…For instance, lovastatin administration to rats has been described to result in a significantly increased liver membrane peroxidizability (Lankin et al, 2007), as would be indicative of a loss of GPx4. Moreover, LDL from patients treated with statins has been shown in several studies to possess decreased antioxidative capacity if properly isolated (Palomä ki et al, 1999;Lankin et al, 2003).…”

Section: Statin-induced Selenoprotein Suppression 1427mentioning

confidence: 99%

Statin-Induced Liver Injury Involves Cross-Talk between Cholesterol and Selenoprotein Biosynthetic Pathways

Kromer

Moosmann²

2009

Mol Pharmacol

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Statins have become the mainstay of hypercholesterolemia treatment. Despite a seemingly clear rationale behind their use, the inhibition of HMG-CoA reductase, these compounds have been shown to elicit a variety of unanticipated and elusive effects and side effects in vivo. Among the most frequently noted side effects of statin treatment are elevations in liver enzymes. Here, we report our finding that atorvastatin, cerivastatin, and lovastatin at clinically common concentrations induce a selective, differential loss of selenoprotein expression in cultured human HepG2 hepatocytes. The primarily affected selenoprotein was glutathione peroxidase (GPx), whose biosynthesis, steady-state expression level, and catalytic activity were significantly reduced with 10 to 100 nM concentrations of the different compounds. Messenger RNA levels of GPx1 and GPx4 were unaffected by statin treatment, pointing at a posttranscriptional mechanism of selenoprotein suppression. Although statins at selenoprotein-modulatory doses were not cytotoxic by themselves, they induced a significantly increased sensitivity of the cells to peroxides, an effect that was largely reversible by supraphysiological concentrations of selenite. We conclude that statins inhibit the expression of inducible selenoproteins by preventing the mevalonate-dependent maturation of the single human selenocysteine-tRNA and may thereby evoke an increased vulnerability of the liver to secondary toxins. Selenoprotein modulation might constitute an important mechanism of statins to bring forth their clinical effects.

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Section: Statin-induced Selenoprotein Suppression 1427mentioning

confidence: 99%

Statin-Induced Liver Injury Involves Cross-Talk between Cholesterol and Selenoprotein Biosynthetic Pathways

Kromer

Moosmann²

2009

Mol Pharmacol

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“…Free radicals take part in various pathological processes, including NSAID-gastropathies, and play a role in the regulation of cell division [8]. The data on the infl uence of statins on free radical oxidation are contradictory [4,5].Here we evaluate the effect of simvastatin on proliferative processes and local free radical status of GM in intact mice and in mice with NSAID-induced ulceroative gastropathy. …”

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confidence: 99%

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confidence: 99%

Effect of HMG-CoA-Reductase Inhibitor on DNA Synthesis and Free Radical Oxidation in the Gastric Mucosa under Normal Conditions and during Indometacin-Induced Ulcerative Process in the Stomach of Albino Mice

et al. 2012

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We studied the effect of simvastatin (24 mg/kg per os for 30 days) on DNA synthesis ((3)H-thymidine autoradiography) and free radical oxidation (chemiluminescent method) in the gastric mucosa of albino mice under normal conditions and in ulcerative process induced by single indometacin administration. Simvastatin treatment activated free radical oxidation, which was seen from enhanced chemiluminescence in the mucosa homogenate (by 1.7-4.6 times). Administration of indometacin against the background of simvastatin treatment potentiated local oxidative stress and inhibited DNA synthesis. Under these conditions, the area of ulcerative lesion in the gastric mucosa increased by 3.0 times.

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“…Еще одним из распространенных побочных эффектов статинов, кроме отмеченных выше, является обнаружение повышенного уровня трансаминаз печени (АЛТ, АСТ) в кровяном русле [3]. Очевидно, что это действие статинов связано с увеличением проницаемости биомембран гепатоцитов, которое, как показано в наших экспериментах, может быть вызвано инициацией свободнорадикального окисления в биомембранах клеток печени при введении статинов [3,5]. Исходя из вышесказанного, назрела необходимость использования в качестве холестерин-снижающих препаратов лекарственных средств, имеющих механизм действия отличный от статинов.…”

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“…Если наше предположение верно, выявленная негативная корреляция между уровнями гидроперокси-ацилов и холестерина в ЛНП при терапии ингибиторами ГМГ-КоА-редуктазы, напротив, отражает существенное нарушение нормальных механизмов регуляции жидкостности ЛНП и биомембран. Можно думать, что нарушение подобных механизмов лежит в основе нарушения проницаемости мембран гепатоцитов для АЛТ и АСТ при терапии статинами вследствие увеличения окисленности биомембран этих клеток [5]. Действительно, нам удалось экспериментально подтвердить увеличение проницаемости клеточных биомембран при действии вторичного продукта свободнорадикального окисления липидов МДА [12].…”

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The Influence of Hypolipidemic Therapy on the Level of Modified Low Density Lipoproteides

2018

Self Cite

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Aim.To assess the influence of coronary heart disease patients (CHD) therapy with statins or PCSK9 inhibitors influence on the level of oxidatively modified low density lipoproteides (LDL) and activity of erythrocyte Se-glutathione peroxidase (GSH-Px).Materialand methods.To the study, CHD patients were included (9-10 males per group), who during 6 months were undergoing statin therapy — 40 mg per day of pravastatin (group 1) or 0,4 mg per day of cerivastatin (group 2), as the therapy with PCSK9 inhibitor — 420 mg per month evolocumab (group 3) during 1 year. The level of lipohydroperoxide in LDL (LOOH-LDL) was measured in the groups 1 and 2 with the modified method and usage of Fe-xilenolorange; content of oxidized LDL (oxLDL) in the group 3 — with immune chemistry method (assays Mercodia, Sweden). Activeness of GSH-Px in all groups was assessed with the modified methods bound with glutathione reductase system and tret-buthyl hydroperoxide as a substrate.Results.Simultaneously with the decrease of LDL cholesterol in the groups 1 and 2 there was significant increase (in the group 2 — 6-7 times in 3-6 months of therapy) of the level of LOOH-LDL. In the group 2 there was marked significant decrease of GSH-Px activity beginning from the month 3. In the group 3, with decreased LDL cholesterol there was significant decline in oxLDL with changed activity of GSH-Px.Conclusion.Statins, effectively decreasing the level of LDL cholesterol, simultaneously induce the oxidation of LDL and decrease the activity of GSH-Px. Inhibitor PCSK9 not only does effectively decrease the level of LDL cholesterol, but also the content of oxLDL, not leading to decreased GSH-Px activity.

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Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver

Cited by 10 publications

References 11 publications

Statin-Induced Liver Injury Involves Cross-Talk between Cholesterol and Selenoprotein Biosynthetic Pathways

Statin-Induced Liver Injury Involves Cross-Talk between Cholesterol and Selenoprotein Biosynthetic Pathways

Effect of HMG-CoA-Reductase Inhibitor on DNA Synthesis and Free Radical Oxidation in the Gastric Mucosa under Normal Conditions and during Indometacin-Induced Ulcerative Process in the Stomach of Albino Mice

The Influence of Hypolipidemic Therapy on the Level of Modified Low Density Lipoproteides

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