The Effect of the Primula Veris Solid Herbal Extract on the Development of Oxidative Stress and the Functional State of Cardiomyocyte Mitochondria of Rats with Experimental Chronic Heart Failure

Abstract

Experimental chronic heart failure (CHF), caused by intraperitoneal administration of L-isoproterenol (2.5 mg/kg twice a day for 21 days), promotes uncoupling of respiration and oxidative phosphorylation in rat cardiac mitochondria. The rate of mitochondrial oxygen consumption in the metabolic state V3 by Chance in animals with CHF decreased by 53.3% (p < 0.05) with malate (as an oxidation substrate feeding complex I of the electron transport chain (ETC)), by 70.6% (p < 0.05) with succinate (complex II substrate) and by 63.6% (p < 0.05) when malate and succinate were added simultaneously. The respiratory control ratio (RCR) of mitochondria from CHF rats demonstrated a significant decrease for complex I substrate (2.3-fold), complex II substrate (2.5-fold) and 2.6-fold in the case of simultaneous addition of complex I and II substrates and 2.6 times as compared to cardiac mitochondria of intact animals. Mitochondrial dysfunction in experimental CHF is evidently associated with the development of oxidative stress: the malondialdehyde (MDA) content in the group of CHF rats was higher by 54.7% (p < 0.05), as compared with intact animals. The activity of superoxide dismutase (SOD) and catalase was lower by 17.5% (p < 0.05), and by 18.4%, respectively, than in the intact group. Administration of the Primula veris solid herbal extract (PVSHE) attenuated the development of mitochondrial dysfunction in rats with experimental CHF as evidenced by an increase in the V3 respiration using complex I (77.2%; p < 0.05), complex II (114.6%; p < 0.05) substrates and a 1.7- and 2-fold increase in the RCR value (p < 0.05) determined versus negative control with complex I and complex II substrates, respectively. Under these conditions the MDA concentration was lower by 15.7% (p < 0.05), while SOD activity was higher by 56.3% (p < 0.05).