ISO-induced Myocardial Necrosis Research Articles

ERDOSTEINE SALVAGES CARDIAC NECROSIS: NOVEL EFFECT THROUGH MODULATION OF MAPK AND NRF-2/HO-1 PATHWAY

Objective: To assess the pharmacological and molecular effects of erdosteine in ISO induced myocardial necrosis in rats Design and method: To optimize the effect of erdosteine against experimental model of myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6) i.e. normal, ISO-control (ISO-C), erdosteine treatment with ISO. Rats in treatment groups were administered erdosteine orally for 28 days, whereas in normal and ISO-C group, 1% CMC was administered orally at 2 ml/kg/day for 28 days. Two consecutive doses of ISO 85 mg/kg, s.c. were given to ISO-C and erdosteine treatment groups on 27th and 28th day at 24 h interval. On 29th day, hemodynamic parameters were recorded and animals were sacrificed to excise their heart for measurement of various parameters. Results: In ISO-C rats, significantly increased levels of inflammatory markers, pro-oxidants and structural damage was observed as compared to normal group. Furthermore, immunohistochemistry revealed an increased expression of apoptotic proteins and decreased expression of anti-apoptotic protein which was further confirmed through TUNEL assay. Pretreatment with erdosteine at 80 mg/kg and 160 mg/kg reversed the deleterious effects of isoproterenol and normalized myocardial architecture. Erdosteine showed anti-inflammatory and anti-apoptotic activities through inhibition of MAPK pathway. Furthermore, erdosteine partially activated transcription factor Nrf-2 and HO-1 expressions showing the anti-oxidant potential of erdosteine. Conclusions: Thus, this study revealed the new use of an old drug and concluded the protective effect of erdosteine in ISO-induced myocardial necrosis through combined effect of MAPK and Nrf-2/HO-1 pathway.

Cardioprotective potential of polyphenols rich Thraatchathi Chooranam against isoproterenol induced myocardial necrosis in experimental rats

BackgroundThe present study establishes the cardioprotective role of Thraatchathi Chooranam (TC), a polyherbal traditional Siddha medicine, in terms of membrane stabilizing and antioxidant properties in isoproterenol (ISO) induced myocardial necrosis model in rats.MethodsAnimals were divided into six groups (n = 6), normal (received vehicle 0.5% CMC, p.o.), ISO control (received 0.5% CMC + ISO 120 mg/kg, b.w. s.c. twice at an interval of 48 h), standard control (received Vit-E 100 mg/kg, p.o.) + ISO, TC low and high dose (50 and 100 mg/kg p.o., respectively) + ISO, and drug control (received TC at 100 mg/kg, p.o.). At the end of experimental period, blood samples collected and plasma cardiac troponin-I (CTn-I) was measured by ELISA. Cardiac tissues were isolated, levels of membrane stabilizing enzymes, antioxidants and inflammatory markers were estimated. Gene expression of Bax, Bcl2, Caspase 3, HIF-α, TNF-α, iNOS, TRX1 and TrxR were performed by RT-PCR. Histopathological studies on cardiac tissues were conducted using hematoxylin and eosin (H&E) stain. Statistical analyses were performed by one-way ANOVA followed by Tukey’s multiple comparison as post-hoc test.ResultsAdministration of ISO resulted in a significant increase in plasma CTn-I, decrease in superoxide dismutase, glutathione and glutathione peroxidase; it also significantly altered membrane stabilizing enzymes like Na+/K+-ATPase, Mg2+-ATPase Ca2+-ATPase and Cathepsin D. Pretreatment with TC (50 mg/kg and 100 mg/kg) decreased CTn-I, and improved membrane stabilizing and endogenous antioxidant enzymes and decreased cathespin D level in a dose dependent manner. Histopathological examination revealed that TC improves cellular membrane integrity and decreases inflammatory cell infiltration and necrotic death.ConclusionThe present study provided a strong evidence on the protective effects of TC against ISO-induced myocardial necrosis in rats.

Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf-2/HO-1 pathway.

Isoproterenol (ISO) induced oxidative stress and inflammation is involved in the pathogenesis of myocardial necrosis. To optimize the effect of erdosteine against myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6), that is, normal, ISO-control, erdosteine pretreatment with ISO. Rats were administered erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to ISO-C and erdosteine treatment groups on the 27th and 28th day. On the 29th day, hemodynamic parameters were recorded and the heart was excised for further parameters. In ISO-C rats, significantly increased levels of inflammatory markers, pro-oxidants, and structural damage were observed as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed an increased expression of apoptotic proteins. Erdosteine at 80 mg/kg reversed the deleterious effects of ISO and normalized myocardium. Erdosteine showed anti-inflammatory, antiapoptotic, and antioxidant activities through inhibition of MAPK and Nrf-2/HO-1 pathways. To conclude, erdosteine was found protective in ISO-induced myocardial necrosis through MAPK and Nrf-2/HO-1 pathway.

Protective role of wild garlic on isoproterenol-induced myocardial necrosis in wistar rats

Ethnopharmacological relevanceTulbaghia violacea Harv. (TVL) is a folk medicine, native to South Africa which has previously shown antioxidant, anti-hypertensive and anti-diabetic effects. The Aim of the study: The aim of the current study was to investigate the protective role of wild garlic or TVL on isoproterenol (ISO)-induced myocardial necrosis in rats. Materials and methodsAnimal (n = 6 each group) were pre and co-treated with TVL (60 mg/kg body weight) daily for 30 days. Myocardial necrosis was administrated by subcutaneous injection of ISO (85 mg/kg body weight) into rats on 29th and 30th day. On the 31st day, rats were anaesthetized and blood, heart samples were obtained for the biochemical, histopathological and molecular study. The specific protein target analysis from TVL was done by reverse docking study (reverse pharmacophore mapping) using PharmMapper. ResultsThe levels of cardiac markers, lipid peroxidation products, and heart rate were considerably increased in ISO-induced myocardial necrosis in rats whilst plasma enzymatic antioxidants were significantly decreased. Myocardial necrotic mRNA genes were increased in ISO-induced myocardial necrosis in rats compared to controls. Pre and co-treatment with TVL and ramipril of myocardial necrosis in rats showed significant effects on all the biochemical and molecular studies evaluated. TVL reduced heart rate, prevented oxidative stress and downregulated the Fas-receptor and caspase-mediated apoptosis-signaling pathway, and heart muscle damage in myocardial necrosis in rats. The specific target protein [disulfide, bis (2-sulfhydrylethyl] from TVL mediates the protective effects. ConclusionWild garlic or TVL extract has shown a protective effect on ISO-induced myocardial necrosis in rats by increasing antioxidant production confirmed with docking studies.

Protective effect of omeprazole and lansoprazole on β-receptor stimulated myocardial infarction in Wistar rats.

We investigated the effect of omeprazole (OPZ) and lansoprazole (LPZ) on the pathophysiology of myocardial necrosis in rats by inspecting a series of indicators like hemodynamic parameters, biochemical estimations and histopathological changes in the myocardial tissue. Rats received either OPZ, LPZ (50mg/kg/day, p.o.) individually for 7days with concurrent administration of isoproterenol (ISO) (150mg/kg, s.c.) on 6th and 7th day of study period to induce myocardial infarction. On the 8th day after measuring hemodynamic parameters, rats were killed and parameters were evaluated. ECG waves were found to be normal in the treatment group. ISO control rats revealed escalation in the oxidative stress as evidenced by depletion in the content of SOD, GSH, catalase and increase in the level of MDA and NO as compared with the normal rats. Treatment with OPZ and LPZ significantly reduced the ROS, indicated by an increase in the endogenous antioxidants and a decrease in NO and MDA levels. ISO control rats showed a significant elevation in the levels of pro-inflammatory cytokine TNF-α as compared to the normal and treatment group of rats. Administration of OPZ and LPZ does not exhibit any significant toxicity. Our findings reveal that multiple doses of OPZ and LPZ may have distinctly minimized the ISO-induced myocardial necrosis by declining the hmodynamic parameters, oxidative stress and pro-inflammatory cytokine TNF-α in myocardial infarcted rats.

Cardioprotective effect of ‘Khamira Abresham Hakim Arshad Wala’ a Unani formulation in isoproterenol-induced myocardial necrosis in rats

The present study was designed to investigate whether Khamira Abresham Hakim Arshad Wala (KAHAW), a preparation of Unani System of Medicine, is able to attenuate the isoproterenol (ISO)-induced myocardial necrosis on the basis of its effects on hemodynamic, antioxidant, histopathological and ultrastructural parameters. Male Wistar albino rats were administered KAHAW (200, 400 and 800 mg/kg/day, orally) or vehicle for 14 days with concurrent ISO administration (85 mg/kg, subcutaneously, 2 doses at 24 h interval) on 13th and 14th day. On the 15th day, vehicle+ISO-treated rats exhibit cardiac dysfunctions as indicated by decrease in systolic, diastolic, and mean arterial pressures, reduction in both maximum positive and maximum negative rates of developed left ventricular pressure (±LVdp/dt) and an increase in left ventricular end-diastolic pressure (LVEDP). Biochemical analysis of their heart homogenate presented reduced levels of enzymes viz., superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) isoenzyme. A marked reduction in reduced glutathione (GSH) levels along with increase in levels of thiobarbituric acid reactive substances (TBARS) was also observed in rat myocardium. Myocardial necrosis, edema and inflammation were evident from the light microscopic and ultrastructural changes. KAHAW at dose of 800 mg/kg/day significantly reversed majority of hemodynamic and antioxidant derangements. The protective role of KAHAW on ISO-induced myocardial necrosis was further confirmed by histopathological and ultrastructural examination. There was no significant change in heart rate in all experimental groups. KAHAW per se groups showed no significant change when compared with vehicle control group. The study results thus demonstrated the cardioprotective potential of KAHAW against ISO-induced myocardial necrosis and associated oxidative stress.

Effect of D-003 on isoproterenol-induced myocardial necrosis in rats.

D-003 is a mixture of high-molecular-weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isoproterenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objective of this study was to determine whether D-003 shows protective effects against ISO-induced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25-400 mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5-200 mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investigated. D-003 administered as single doses dose-dependently decreased necrosis area, percent of infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, but only the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment with ASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs was unchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necrosis indicators in a dose-dependent manner, with results effective from 25 mg/kg to the highest dose tested, indicating that the repeated dose scheme was more effective to prevent the damage. It is concluded that D-003 shows a protective effect on the myocardial necrosis induced by ISO in rats.