Protective effect of hydroalcoholic extract of Andrographis paniculata on ischaemia-reperfusion induced myocardial injury in rats.
ABSTRACT Protecting myocardium from ischaemia-reperfusion (I-R) injury is important to reduce the complication of myocardial infarction (MI) and interventional revascularization procedures. In the present study, the cardioprotective potential of hydroalcoholic extract of Andrographis paniculata was evaluated against left anterior descending coronary artery (LADCA) ligation-induced I-R injury of myocardium in rats.
MI was induced in rats by LADCA ligation for 45 min followed by reperfusion for 60 min. The rats were divided into five experimental groups viz., sham (saline treated, but LADCA was not ligated), I-R control (saline treated + I-R), benazepril (30 mg/kg + I-R), A. paniculata (200 mg/kg per se) and A. paniculata (200 mg/kg + I-R). A. paniculata was administered orally for 31 days. On day 31, rats were subjected to the I-R and cardiac function parameters were recorded. Further, rats were sacrificed and heart was excised for biochemical and histopathological studies.
In I-R control group, LADCA ligation resulted in significant cardiac dysfunction evidenced by reduced haemodynamic parameters; mean arterial pressure (MAP) and heart rate (HR). The left ventricular contractile function was also altered. In I-R control group, I-R caused decline in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) as well as leakage of myocytes injury marker enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH), and enhanced lipid peroxidation product, malonaldialdehyde (MDA). However, rats pretreated with A. paniculata 200 mg/kg showed favourable modulation of haemodynamic and left ventricular contractile function parameters, restoration of the myocardial antioxidants and prevention of depletion of myocytes injury marker enzymes along with inhibition of lipid peroxidation. Histopathological observations confirmed the protective effects of A. paniculata. The cardioprotective effects of A. paniculata were found comparable to that of benazepril treatment. Interpretation &
Our results showed the cardioprotective effects of A. paniculata against I-R injury likely result from the suppression of oxidative stress and preserved histoarchitecture of myofibrils along with improved haemodynamic and ventricular functions.
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ABSTRACT: The oxidation of phenylhydrazine in buffered aqueous solutions is a complex process involving several intermediates. It can be initiated by metal cations, such as Cu2+; in which case EDTA acts as an inhibitor. It can also be intiated by oxyhemoglobin; in which case chelating agents do not interfere. Superoxide radical is both a product of this reaction and a chain propagator. The formation of O2- could be demonstrated in terms of a reduction of nitroblue tetrazolium, which was prevented by superoxide dismutase. The importance of O2- in carrying the reaction chains was shown by the inhibition of phenylhydrazine oxidation by superoxide dismutase. Hydrogen peroxide accumulated during the reaction and could be detected with catalase. The progress of this oxidation could be monitored in terms of oxygen consumption and by following increases in absorbance at 280 or 320 nm. The oxidation was markedly autocatalytic and superoxide dismutase had the effect of extending the lag period. The absorbance at 280 nm was due to an intermediate which first accumulated and was then consumed. This intermediate appears to be benzendiazonium ion. The absorbance at 320 nm was due to a stable product, which was not identified. The time course of oxygen consumption paralleled the increase in absorbance at 320 nm and lagged behind the changes at 280 nm. Exogenous benzenediazonium ion accelerated the oxidation of phenylhydrazine and eliminated the lag phase. Benzenediazonium ion must therefore react with phenylhydrazine to produce a very reactive intermediate, possibly phenyldiazene. A mechanism was proposed which is consistent with the data. The intermediates and products of the oxidation of phenylhydrazine include superoxide radical, hydrogen peroxide, phenylhydrazyl radical, phenyldiazene, and benzenediazonium ion. This is a minimal list: others remain to be detected and identified. It appears likely that the diverse biological effects of phenylhydrazine are largely due to the reactivities of these intermediates and products.Biochemistry 03/1976; 15(3):681-7. · 3.42 Impact Factor
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ABSTRACT: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formation increases in the post-ischemic myocardium and represents a mechanism of post ischemic injury. ROS, which are formed during reperfusion, trigger lipid peroxidation, oxidize proteins and cause DNA strand breaks, all interfering with and potentially damaging normal cellular function. Oxidative stress is associated with poor recovery of left ventricular function after a sustained period of ischemia and, according to several studies, it contributes significantly to the acceleration of necrosis and thus extension of infarction, apoptosis, arrhythmiogenesis and endothelial dysfunction. Accordingly, targeting the generation of ROS with various antioxidants has been shown to improve left ventricular function after the restoration of flow. Apart from mechanical or pharmacological interventions that open the occluded artery, the heart has endogenous mechanisms of protection, called ischemic pre-conditioning and ischemic post-conditioning. Opening of the mitochondrial ATP-sensitive potassium channels and subsequent generation of ROS is considered to be a pivotal step in the mechanisms of pre- and post-conditioning. Notably, ROS play an ambiguous role in the protection of myocardium and can be both effective and harmful. Thus, the role of antioxidants in the attenuation of the effects of pre-and post-conditioning in vivo remains controversial.Expert opinion on therapeutic targets 07/2009; 13(8):945-56. · 3.72 Impact Factor
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ABSTRACT: Autophagy is a catabolic process through which damaged or long-lived proteins, macromolecules, or organelles are recycled by using lysosomal degradation machinery. Although the occurrence of autophagy in several cardiac diseases including ischemic or dilated cardiomyopathy, heart failure, hypertrophy, and during ischemia/reperfusion injury have been reported, the exact role of autophagy in these diseases is not known. Emerging studies indicate that oxidative stress in cellular system could induce autophagy, and oxidatively modified macromolecules and organelles can be selectively removed by autophagy. Mild oxidative stress-induced autophagy could provide the first line of protection against major damage like apoptosis and necrosis. Cardiac-specific loss of Atg5, an autophagic gene involved in the formation of autophagosome, causes cardiac hypertrophy, left ventricular dilation, and contractile dysfunction. Recently, it was revealed that Atg4, another autophagic gene involved in the formation of autophagosomes, is controlled through redox regulation under the condition of starvation-induced autophagy. In this review, we discuss the function of autophagy in association with oxidative stress and redox signaling in the remodeling of cardiac myocardium. Further research is needed to explore the possibilities of redox regulation of other autophagic genes and the role of redox signaling-mediated autophagy in the heart.Antioxidants & Redox Signaling 03/2009; 11(8):1975-88. · 8.20 Impact Factor