Isoproterenol-induced Cardiotoxicity Research Articles

Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity

Abstract Panax japonicus has long been utilized as an herbal remedy in Chinese traditional medicine for treating various diseases. In this investigation, we present the environmentally friendly silver nanoparticle (AgNP) synthesis by the aqueous extract of P. japonicas to follow its cardioprotective effects. Through various analytical methods, we identified the nanoparticles (NPs). Our XRD findings revealed the formation of Ag@P. japonicus, while FE-SEM imagery indicated a spherical shape, with NPs measuring less than 40 nm. The UV–Vis and FT-IR spectroscopy confirm the green synthesis of Ag@P. japonicus. In the medicinal section, 45 Wistar rats were utilized. These groups consisted of a normal group, a group that was solely treated with isoproterenol for inducing myocardial infarction, and two groups that were pretreated with AgNPs at different doses for 14 days. These pretreated groups were then challenged with isoproterenol. The expression of PI3K/Akt/mTOR and other downstream inflammatory and apoptotic mediators were followed. Additionally, the expression of Keap1, Nrf2, ECG, cardiac markers, and other downstream antioxidant enzymes were assessed. Treatment with AgNPs ameliorated the apoptosis, inflammation, and myocardial autophagy, regulated the PI3K/Akt/mTOR pathway, increased the antioxidant enzyme efficacies, and activated the Keap1/Nrf2/HO-1 pathway. The findings suggest that AgNPs may have a cardioprotective efficacy on myocardial infarction by mitigating the Keap1/Nrf2 pathway, GST, GPx, GSH, SOD, IL-1β, IL-6, TNF-α, NF-κB, Bax, Bcl2, caspase-9, caspase-3, and PI3K/Akt/mTOR pathway. Furthermore, the treatment decreased the infarct region size, attenuated the cardiac indicators levels, and mitigated immune cell infiltration and myocardial necrosis.

Effects of Taraxerol on Oxidative and Inflammatory Mediators in Isoproterenol-Induced Cardiotoxicity in an Animal Model.

Myocardial infarction (MI) continues to be an important issue in healthcare systems worldwide, leading to high rates of morbidity and mortality. Despite ongoing efforts towards the development of preventive measures and treatments, addressing the challenges posed by MI remains difficult both in developed and developing countries. However, researchers recently investigated the potential cardioprotective effects of taraxerol utilizing an isoproterenol (ISO)-induced cardiotoxicity model among Sprague Dawley rats. Specifically, subcutaneous tissue injections consisting of 5.25 mg/kg or 8.5 mg/kg ISO were administered over two consecutive days as stimuli to induce cardiac injury. To investigate the possibility of preventing damage caused by ISO-induced cardiotoxicity by taraxerol treatment, five groups were formed: a normal control group (1% Tween 80), an ISO control group, an amlodipine group administered 5 mg/kg/day, and various doses of taraxerol. The study results showed that treatment significantly reduced cardiac marker enzymes. Additionally, pretreatment with taraxerol increased myocardial activity in SOD and GPx, leading to significant reductions in serum CK-MB levels along with MDA, TNF-α, and IL-6. Further histopathological analysis supported these observations, as treated animals had less cellular infiltration compared to untreated ones. These multifaceted findings suggest that oral administration of taraxerol could potentially protect hearts from ISO-caused damage by increasing endogenous antioxidant concentrations while decreasing pro-inflammatory cytokines.

Decalepis hamiltonii and its bioactive constituents mitigate isoproterenol-induced cardiotoxicity in aged rats

Aging is associated with functional decline and structural deteriorations of the myocardium and plays a crucial role in cardiovascular ailments. Decalepis hamiltonii ( Dh ) is well known medicinal plant used in traditional medicine and exhibits potent antioxidant properties. Therefore, the current study was proposed to assess the cardioprotective potential of Dh extract and its bioactive constituents [Ellagic acid (EA) and 4‑hydroxyisophthalic acid (4-HIA)] against isoproterenol (ISO)-induced region-specific myocardial damage in aging rats. Male albino Wistar rats aged 22 months were administered orally with Dh extract (100mg/kg BW), EA (50 mg/kg BW), and 4‑HIA (30 mg/kg BW) for one month before inducing MI using ISO (150 mg/kg BW) for the consecutive last two days. The ISO group exhibited a significant increase in hemodynamic parameters, cardiac marker enzymes, serum lipids, and oxidative stress markers. A significant reduction in region-specific antioxidant enzymes levels and histopathological alterations were observed in ISO-treated rats. Whereas, pretreatment of EA, 4-HIA, and Dh extract reduced the cardiac dysfunction biomarkers and mitigated oxidative stress by enhancing antioxidant enzymes and restoring histopathological changes in ISO-treated rats. The Overall findings give insights into the therapeutic applications of Dh extract and its compounds in ameliorating cardiovascular disorders through its antioxidant potential.

Zingiberene Protects from Isoproterenol-Induced Cardiotoxicity via Attenuation of Hyperlipidemia and Oxidative Stress in Rats

Zingiberene Protects from Isoproterenol-Induced Cardiotoxicity via Attenuation of Hyperlipidemia and Oxidative Stress in Rats

Gallic acid protects against isoproterenol-induced cardiotoxicity in rats.

Gallic acid (GA) is a polyphenolic agent with interesting pharmacological impacts on the cardiovascular system. The present study purposed to study the protective effects of GA at 25 and 50mg/kg against isoproterenol (ISO)-induced cardiac damage in ischemia/reperfusion (I/R) in rats. Male Wistar rats were randomly assigned into six groups: Control, Control treated with GA at 25mg/kg (GA25), Control treated with GA at 50mg/kg (GA50), Hypertrophic rats induced by ISO (ISO), Hypertrophic rats treated with GA at 25mg/kg (ISO+GA25), and Hypertrophic rats treated with GA at 50mg/kg (ISO+GA50). Heart isolation was performed to induce a cardiac I/R injury model. Cardiac hemodynamic parameters were recorded. Serum Lactate Dehydrogenase (LDH) and Creatine Kinase-MB (CK-MB) and cardiac Superoxide dismutases (SOD) levels were evaluated. The gene expression of Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) was assessed. We found that GA at 50mg/kg was significantly increased cardiac function at post I/R period in ISO-induced hypertrophic hearts. Moreover, it suppressed cardiac hypertrophy, the serum LDH and CK-MB levels in ISO injected rats. Administration of GA at 50mg/kg was significantly increased SOD level and SERCA2a gene expression in the hypertrophic hearts. GA at 50mg/kg could improve cardiac performance possibly by increasing antioxidant defense enzymes, reducing cell damage, and enhancing SERCA2a gene expression in hypertrophic heart induced by ISO in I/R injury conditions.

Evaluation of cardioprotective potential of isolated swerchirin against the isoproterenol-induced cardiotoxicity in wistar albino rats

Background: Cardiotoxicity is one of the emerging health-care issues worldwide and mortality due to this is increasing exponentially. Oxidative stress, myocardial inflammation, and damage to the cardiac membrane are major causative attributes for this toxicity. Isoproterenol (ISO)-induced cardiotoxicity is a well-established and accepted model to estimate innovative cardioprotective agents, as it exhibits several morphological and biochemical aberrations in the myocardium of rat that is comparable with those detected in clinical practice. Objectives: In the present study, we explored the cardioprotective effect of swerchirin (SW) extracted from Swertia chirayita in the ISO model. Materials and Methods: SW was isolated from S. chirayita, characterized by high-performance thin-layer chromatography-mass spectrometry, 1H-nuclear magnetic resonance (NMR), 13C-NMR, and high-performance liquid chromatography techniques. The in-vitro study was performed for 2,2-Diphenyl-1-picrylhydrazyl and nitric oxide scavenging activity to explore the antioxidant capacity. In silico study was performed to ascertain the binding affinity of SW with antioxidant enzymes. The in-vivo study was performed to explore the cardioprotective activity in the ISO-induced cardiotoxic model. Results: The in vitro studies showed the significant antioxidant potential of SW whereas the in silico study revealed its effective binding into the catalytic pocket domain of superoxide dismutase and catalase. The in vivo study showed a significant improvement in antioxidant enzymes and a reduction in serum glutamic-oxaloacetate transaminase and lipid profile. Further, SW also significantly reversed the histopathological aberrations in a dose-dependent manner. Conclusion: Findings of the study showed a significant cardioprotective effect of SW against ISO-induced cardiac damage.

Withania Somnifera: Correlation of Phytoconstituents with Hypolipidemic and Cardioprotective Activities

Withania somnifera (WS) (Dunal) or Ashwagandha is a well-known hypolipidemic herb and antioxidant. In this study, 75% ethanolic extract of WS is attempted to evaluate the cardioprotective activity of isoproterenol-induced cardiotoxicity and hypolipidemic activity in Triton WR 1339-induced hyperlipidemia. In addition, phytochemical evaluation of the same extracts analyzed by gas chromatography–mass spectrometer (GC–MS). This study found that 7 days of therapy with WS extracts at 1000 mg/kg b.wt. reduced cholesterol by 76%, low-density lipoprotein (LDL) by 71%, and TAG by 12% (P < 0.05). Furthermore, it can significantly reduce cholesterol and LDL levels (P < 0.05). Similarly, the use of 50 mg/kg b.wt. of WS extract showed a cardioprotective effect against isoproterenol-induced cardiac toxic rats. The antioxidants glutathione, glutathione peroxidase, and catalase are increased in WS extract (P < 0.05), whereas the release of cardiac indicators in heart tissue is reduced (P < 0.05). Furthermore, a 30-day treatment with WS also reduced triacylglycerol in isoprenaline-induced cardiotoxic rats. GC–MS analysis of the methanol fraction of the Ashwagandha 70% ethanolic extract showed the presence of higher concentrations of fatty acids. In conclusion, WS showed hypolipidemic and cardioprotective activities in diseased animals induced by isoproterenol and Triton WR 1339.

Evolution of β-catenin-independent Wnt-GSK3-mTOR signalling in regulation of energy metabolism in isoproterenol-induced cardiotoxicity model.

Isoproterenol (ISO) is widely used agent to study the effects of interventions which could prevent or attenuate the development of myocardial infarction. The sequence of pathological event's revealed that increased myocardial tissue oxygen demand and energy dysregulation exist early during Iso-induced cardiac toxicity. Later, tissue hypoxia results in increased oxidative stress, inflammation and fibrosis along with cardiac dysfunction in this model. The canonical Wnt/β-catenin pathway has been reported to directly implicate in inducing cardiomyocyte hypertrophy and remodelling. However, less is known about the role of non-canonical Wnt signalling in cardiac diseases. Certain evidences have suggested that the activation of Wnt could up-regulate key energy sensor and cell growth regulator mTOR (Mechanistic target of rapamycin) by inhibition of GSK-3β mediator. The GSK-3β could negatively influence the mTOR activity and produce energy dysregulation during stress or hypoxic conditions. This suggests that the inhibition of GSK-3β by Wnt signalling could up-regulate mTOR levels and thereby restore early myocardial tissue energy balance and prevent cardiac toxicity in rodents. We hereby discuss a novel therapeutic role of the β-catenin independent, Wnt-GSK3-mTOR axis in attenuation of Iso-induced cardiotoxicity in rodents.

Protective Effect of Geraniol on Oxidative, Inflammatory and Apoptotic Alterations in Isoproterenol-Induced Cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR Pathways

Background: Myocardial infarction (MI) is still a major contributor to mortality worldwide, and therefore, searching for new drugs is an urgent priority. Natural products are a renewable source for medicinally and pharmacologically active molecules. The objective of this study was to explore the potential of geraniol, a monoterpene alcohol, to protect against MI. Methods: Five groups of Wister rats were used: a control group; a group treated only with geraniol; a group treated only with isoproterenol, to induce MI; and two groups pretreated with geraniol (100 or 200 mg/kg, respectively) for 14 days and challenged with isoproterenol on the 13th and 14th days. Several parameters were measured including electrocardiogram (ECG), cardiac markers, the expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and other downstream antioxidant enzymes, as well as the expression of phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and other downstream apoptotic and inflammatory mediators. Results: Geraniol treatment reduced the size of the infarct region, attenuated the levels of cardiac indicators, and diminished myocardial necrosis and immune cell infiltration. Geraniol treatment also activated the Keap1/Nrf2/heme oxygenase-1 (HO-1) pathway, increased antioxidant enzyme activities, modulated the PI3K/Akt/mTOR pathway, and ameliorated myocardial autophagy, inflammation, and apoptosis. Conclusion: Geraniol may possess a protective effect against MI through moderating MI-induced myocardial oxidative stress (glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and Keap1/Nrf2 pathway), inflammation (IL-1β, IL-6, TNF-α, and Nuclear factor-κB (NF-κB)), apoptosis (caspase-3, caspase-9, Bcl2, and Bax), and autophagy (PI3K/Akt/mTOR pathway).

Serum miR-206 as a biomarker for drug-induced skeletal muscle injury in rats.

Creatine kinase (CK) and lactate dehydrogenase (LDH) serve as biomarkers for skeletal muscle injury in preclinical toxicity studies, but have a limitation regarding tissue specificity. Circulating miR-206 was recently reported to be a useful biomarker for skeletal muscle disorders in humans. Here, we sought to determine whether serum miR-206 can be used as a biomarker in preclinical toxicity studies to detect drug-induced skeletal muscle injury with higher sensitivity and specificity than the biomarkers CK, LDH, skeletal troponin I (sTnI), and myosin light chain 3 (Myl3). We established rat models of skeletal muscle injury through treatment with the muscle toxicant 2,3,5,6-tetramethyl-p-phenylenediamine (TMPD) as well as four in-house compounds. We found that serum miR-206 levels significantly increased after treatment with TMPD, and tended to be higher in rats treated with in-house compounds than in control rats. ROC analysis revealed that the specificity of serum miR-206 for detection of skeletal muscle injury was higher compared with those of other markers. Further, serum miR-206 levels were unchanged in rats with isoproterenol-induced cardiotoxicity. These findings demonstrate that serum miR-206 may serve as a highly specific biomarker for preclinical analysis of rats with drug-induced skeletal muscle injuries.

Cardioprotective Potentials of Aqueous Extract of Chrysophyllum Albidum (G. Don-Holl.) Pulp on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

Cardiovascular diseases are the number one cause of death globally. A number of medicinal plants have shown their beneficial effect on cardiovascular system. The study investigated the cardioprotective potential of aqueous C. albidium pulp extract on isoproterenol-induced cardiotoxicity. The extract of C. albidum was screened for the presence of phytochemicals and the concentrations of phenolics and total flavonoids were also evaluated. Male wistar rats (30) were equally grouped into five. Group 1 rats received normal saline only, Group 2 rats received normal saline and induced with ISO, Group 3 rats were orally pretreated with propanolol and induced with ISO while Group 4 and 5 rats were orally pretreated with 100mg/kg bwt and 200mg/kg bwt C. albidum pulp respectively and induced with ISO. The activities of CK-MB, LDH, ALT, AST and the concentrations of lipid profile were estimated in the blood plasma of the experimental rats. Data was analyzed using appropriate descriptive and inferential statistics. The findings of the study revealed the presence of phytochemicals such as alkaloids, tannins, flavonoids, cardiac glycosides. There was a significant decrease in the activities of CK-MB, LDH, ALT and AST in the plasma of the pretreated C. albidum pulp extract groups. Pretreatment with the C. albidum pulp extract at 100mg/kg bwt and 200mg/kg bwt caused significant alterations in the lipid profile of the animals. The result of this study suggested that aqueous C. albidum pulp extract may serve as a potential cardioprotective agent against cardiovascular diseases.

The Role of Autophagy and Death Pathways in Dose-dependent Isoproterenolinduced Cardiotoxicity.

Background:Isoproterenol (ISO) is a non-selective β-adrenergic agonist. Our aims were to investigate the autophagy and cell death pathways including apoptosis and necrosis in ISO-induced car-diac injury in a dose-dependent manner.Methods:Male Sprague-Dawley rats were treated for 24 hours with I. vehicle (saline); II. 0.005 mg/kg ISO; III. 0.05 mg/kg ISO; IV. 0.5 mg/kg ISO; V. 5 mg/kg ISO; VI. 50 mg/kg ISO, respectively. Hearts were isolated and infarct size was measured. Serum levels of Troponin T (TrT), lactate dehydrogenase (LDH), creatine kinase iso-enzyme MB (CK-MB) were measured. TUNEL assay was carried out to monitor apoptotic cell death and Western blot was performed to evaluate the level of autophagic and apoptotic markers.Results:Survival rate of animals was dose-dependently decreased by ISO. Serum markers and infarct size revealed the development of cardiac toxicity. Level of Caspase-3, and results of TUNEL assay, demonstrated that the level of apoptosis was dose-dependently increased. They reached the highest level in ISO 5 and it decreased slightly in ISO 50 group. Focusing on autophagic proteins, we found that level of Beclin-1 was increased in a dose-dependent manner, but significantly increased in ISO 50 treated group. Level of LC3B-II and p62 showed the same manner, but the elevated level of p62 indicated that autophagy was impaired in both ISO 5 and ISO 50 groups.Conclusion:Taken together these results suggest that at smaller dose of ISO autophagy may cope with the toxic effect of ISO; however, at higher dose apoptosis is initiated and at the highest dose substantial necrosis occurs.

Suppression of isoproterenol-induced cardiotoxicity in rats by raspberry ketone via activation of peroxisome proliferator activated receptor-α

The peroxisome proliferator-activated receptor-α (PPAR-α) controls the lipid and glucose metabolism and also affects inflammation, cell proliferation and apoptosis during cardiovascular disease. Raspberry ketone (RK) is a red raspberry (Rubusidaeus, Family-Rosaceae) plant constituent, which activates PPAR-α. This study was conducted to assess the cardioprotective action of RK against isoproterenol (ISO)-induced cardiotoxicity. Wistar rats were randomly divided into six groups (six rats/group). Rats were orally administered with RK (50, 100 and 200 mg/kg, respectively) and fenofibrate (standard, 80 mg/kg) for 28 days and ISO was administered (85 mg/kg, subcutaneously) on 27th and 28th day. Administration of ISO in rats significantly altered hemodynamic and electrocardiogram patterns, total antioxidant capacity, PPAR-α, and apolipoprotein C-III levels. These myocardial aberrations were further confirmed during infarct size, heart weight to body weight ratio and immunohistochemical assessments (caspase-3 and nuclear factor-κB). RK pretreatment (100 and 200 mg/kg) significantly protected rats against oxidative stress, inflammation, and dyslipidemia caused by ISO as demonstrated by change in hemodynamic, biochemical and histological parameters. The results so obtained were quite comparable with fenofibrate. Moreover, RK was found to have binding affinity with PPAR-α, as confirmed by docking analysis. PPAR-α expression and concentration was also found increased in presence of RK which gave impression that RK probably showed cardioprotection via PPAR-α activation, however direct binding study of RK with PPAR-α is needed to confirm this assumption.

Periostin alters transcriptional profile in a rat model of isoproterenol-induced cardiotoxicity.

Periostin is an extracellular matrix protein from the fasciclin family that guides cellular trafficking and extracellular matrix organization. Periostin stimulates mature cardiomyocytes to reenter the cell cycle. The molecular mechanism behind such stimulation remains to be explored. A DNA microarray technology constituting 30,429 gene-level probe sets was utilized to investigate effects of recombinant murine periostin peptide on the gene expression pattern in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1) control group, (2) only periostin applied group, (3) ISO cardiotoxicity group, and (4) ISO + periostin group. The experiment was continued for 28 days, and rats were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that periostin significantly altered the expression of at least ±2-fold of 2474 genes in the ISO + periostin group compared to the ISO cardiotoxicity group of which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway analysis indicated that multiple pathway networks were affected by periostin, with predominant changes occurring in the expression of genes involved in oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-α NF-κB signaling pathways. These findings indicate that periostin alters gene expression profile in the ISO-induced myocardial injury and modulates local myocardial inflammation, possibly mitigating inflammation through TNF-α NF-κB signaling pathway along with a decreased Casp7 activity and apoptotic cell death.

Attenuation of isoproterenol-induced cardiotoxicity in rats by Narirutin rich fraction from grape fruit

BackgroundOxidative stress is one of the major mechanism involved in pathogenesis of myocardial infarction. Use of natural products as therapeutic approach for ischemic myocardial injury is gaining attention worldwide. PurposeThis study was designed to investigate efficacy of Narirutin rich fraction (NRF), obtained from grape fruit peel, in the treatment of isoproterenol induced myocardial infarction in rats. MethodsAfter 3-days pretreatment with NRF (100 mg/kg and 200 mg/kg, p.o.) myocardial injury was induced by subcutaneous administration of isoproterenol (85 mg/kg) for 2 days. Hemodynamic parameters, biochemical parameters, histological and ultrastructural changes were observed. ResultsIsoproterenol induced myocardial injury was evidenced by significant alterations in ECG, mean arterial pressure and left ventricular functions. Myocardial creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level were reduced while MDE levels were increased. Histological findings also showed severe changes. Treatment with NRF significantly attenuated these parameters in dose dependent manner. ConclusionThus, present study provides evidences for efficacy of NRF against isoproterenol induced myocardial infarction in rats.

Paradoxical effects of atorvastatin in isoproterenol-induced cardiotoxicity in rats: Role of oxidative stress and inflammation

Atorvastatin (ATV) was previously shown to improve oxidative stress, inflammation and endothelial dysfunction in several experimental and clinical studies yet other studies have reported a pro-oxidant and damaging effect upon ATV administration. The present study was directed to investigate the effect of ATV pre- and post-treatment in isoproterenol (ISO)-induced cardiotoxicity in rats. Myocardial damage was induced by ISO (5 mg/kg/day, s.c.) for 1 week. ATV (10 mg/kg/day, p.o.) was given for 2 weeks starting 1 week before or after ISO administration. ISO-treated rats showed significant alterations in electrocardiographic recordings, serum creatine kinase-MB (CK-MB) level as well as oxidative stress and inflammatory biomarkers. Moreover, ISO administration resulted in endothelial dysfunction and significant histopathological damage. Pre-treatment with ATV aggravated ISO-induced cardiotoxicity. On the other hand, ATV post-treatment succeeded to significantly improve oxidative stress and inflammatory biomarkers, endothelial dysfunction and myocardial degeneration. These results suggest that ATV might produce a synergistic pro-oxidant effect if given before or along with another pro-oxidant (ISO). Thus, caution should be applied upon the use of statin as a prophylactic therapy for primary cardiovascular disease prevention.

Effect of cyclodextrin garcinol complex on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

Effect of cyclodextrin garcinol complex on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

Preventive Effect of Phytic Acid on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

This study was aimed to evaluate the preventive role of phytic acid on membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na+ /K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with phytic acid (25 and 50 mg/kg, respectively) for a period of 56 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days. ISO-induced rats showed a significant decrease in the activity of Na+ /K+ ATPase and increase in the activities of Ca2+ and Mg2+ ATPase in the heart and a significant (P<0.05) increase in the levels of glycoproteins in serum and the heart were also observed in ISO-induced rats. Pretreatment with phytic acid for a period of 56 days exhibited a significant (P<0.05) effect and altered these biochemical parameters positively in ISO-induced rats. Thus, our study shows that phytic acid has cardioprotective role in ISO-induced MI in rats.

Protective Effect of <i>Bombyx mori</i> L Cocoon (Abresham) and its Formulations against Isoproterenol-Induced Cardiac Damage

Purpose: To investigate the potential activity of Bombyx mori and its formulations against isoproterenol (ISO) induced cardiotoxicity.Methods: Wistar rats were orally pretreated with the ethanol extract of Bombyx mori cocoons in two doses (250 and 500 mg/kg) for 30 days; rats were similarly pretreated with its polyherbal formulations incorporating Khamira Abresham sada (KAS) and Khamira Abresham Hakim Arshadwala (KAHAW) (800 mg/kg), standard drug metoprolol (10 mg/kg) and normal saline for 30 days. Cardiotoxicity was induced by administration of isoproterenol (ISO, 85 mg/kg, subcutaneous) given twice on days 29 and 30 in all six pre-treated groups (n = 6) except the normal control. Cardiotoxicity was assessed by morphological and biochemical evaluation and further confirmed by histopathological studies.Results: Pretreatment with Bombyx mori (500 mg/kg), KAHAW and KAS significantly decreased (p < 0.01) the heart weight:body weight (HW:BW) ratio; significantly decreases the elevated activities of the cardiac marker enzymes, namely, asparate transaminase (AST) (p < 0.01), alanine transaminase (ALT) (p < 0.01), lactate dehydrogenase (LDH) (p < 0.01) ,creatinine kinase (CK-MB) (p < 0.01) and thiobarbituric acid reactive substances (TBARS) (p < 0.01) similar to the standard drug metoprolol (p < 0.01) in ISO-injected rats. Pre-treatment of rats with Bombyx mori (500 mg/kg), KAS, KAHAW and metoprolol challenged with ISO also showed absence of troponin. Pretreatment with B. mori (500 mg/kg), KAHAW and KAS significantly increased the activities of Superoxide dismutase (SOD) (p < 0.01), Tissue glutathione (GSH) (p < 0.01) and catalase (p < 0.01) similar to the standard drug metoprolol (p < 0.01).Conclusion: The findings of this study indicate that Bombyx mori as well as its polyherbal formulations exerts potent cardioprotection against isoproterenol-induced cardiotoxicity. This effect is comparable with that of metoprolol.Keywords: Bombyx mori, Myocardial necrosis, Oxidative stress, Cardiotoxicity, Khamira Abresham, Metoprolol, Isoproterenol

Comparison of the specificity of cardiac troponin I and creatine kinase MB in isoproterenol-induced cardiotoxicity model in rats

The aim of this study was to implement the determination of cardiac markers in preclinical research at our department. For this purpose, the pathophysiological model of acute cardiotoxicity induced by high doses of isoproterenol was used. Isoproterenol hydrochloride was intraperitoneally administrated to 42 Wistar male rats at a dose of 50 mg/kg body weight. Cardiac injury was determined by assessing the concentrations of the cardiac markers (cTnI - cardiospecific troponin I and CKMB - cardiac isoenzyme creatine kinase) in the blood at predetermined time-intervals (2, 4, 6, 12, 24 and 36 h), and confirmed by ECG. Isoproterenol hydrochloride caused an elevation in the plasma concentrations of both markers. The results showed a significant difference (P< 0.01) in the concentrations of cTnI between the experimental and control groups at 2, 4, 6 and 24 h with a maximum peak between the fourth and sixth hour. However, the difference in the concentrations of CKMB between the experimental and control groups was non-significant. This experiment confirmed that cTnI is more cardiospecific than CKMB. It also revealed the possibility to use this marker in preclinical testing.