Cardioprotective Effect of Rhapontigenin in Isoproterenol-Induced Myocardial Infarction in a Rat Model

Pharmacology ◽  
2019 ◽  
Vol 103 (5-6) ◽  
pp. 291-302 ◽  
Author(s):  
Ying Fan

Background/Aims: Rhapontigenin (RPG) is a stilben derivative and is known to bear several effects such as antiallergic, anticoagulative, hypoglycemic, antiangiogenic, and purgative. The investigation was conducted to evaluate the cardioprotective efficacy of RPG in rats having acute myocardial infarction (MI) induced by isoproterenol (ISO). Methods: Animals were divided into 6 groups: group I (control group), group II (ISO-treated), group III (1.0 mg/kg/day RPG and ISO-treated), group IV (2.5 mg/kg/day RPG and ISO-treated), group V (5.0 mg/kg/day RPG and ISO-treated), and group VI (treated with RPG 5.0 mg/kg/day). Various cardiac stress markers, including infarct size and heart/body weight index, were investigated in animals with ISO-induced MI, such as inducible nitric oxide synthase (iNOS), creatinine kinase (CK), lactate dehydrogenase (LD), cardiac troponin-T (CTT), superoxide dismutase (SOD), and malondialdehyde. INOS, p38, caspase-3, and connexin 43 expressions were analyzed in animals. Inflammatory mediators, tissue necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were detected in serum of experimental animals. Results: Group I animals indicated normal levels of biochemical parameters, whereas group II animals indicated high levels of these parameters and successful induction of MI. Pretreatment of animal groups III, IV, and V with RPG revealed amelioration of infarct size, heart/body weight index, CK, LD, CTT in rats, whereas group VI animals were treated only with RPG (5.0 mg/kg/day) and not with ISO. Levels of TNF-α, IL-6, MD, SOD, p38, and iNOS expressions were significantly downregulated by RPG administration (5.0 mg/kg/day). Conclusion: RPG ameliorates MI caused by ISO in rats and provides cardioprotective effect, via anti-inflammatory, antioxidant, and antiapoptotic effect.

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Yongle Sun ◽  
Jing Geng ◽  
Deyu Wang

Aging is the crucial co-morbidity that prevents the full cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Combination therapy as a promising strategy may overcome this clinical problem. This study aimed to investigate the cardioprotective effects of Ginsenoside compound-Mc1 (GMc1) and Dendrobium Nobile Lindl (DNL) in myocardial I/R injury and explore the involvement of the TLR4/NF-κB signaling pathway in aged rats. In vivo I/R injury and myocardial infarction was established by temporary coronary ligation in 22–24 months’ old Sprague Dawley male rats. GMc1 (10 mg/kg) and DNL (80 mg/kg) were administered intraperitoneally for 4 weeks and orally for 14 days, respectively, before I/R injury. Infarct size was measured through triphenyl-tetrazolium-chloride staining. ELISA assay was conducted to quantify the levels of cardiotroponin, and myocardial content of TNF-α and glutathione. Western blotting was employed to detect the expression of TLR4/MyD88/NF-κB proteins. GMc1 and DNL significantly reduced the infarct size to a similar extent ( p < 0.05) but their combined effect was greater than individual ones ( p < 0.01). Combination therapy significantly restored the left ventricular end-diastolic and developed pressures at the end of reperfusion as compared with the untreated group ( p < 0.01). Although the GMc1 and DNL reduced the levels of inflammatory cytokine TNF-α and increased the contents of antioxidant glutathione significantly, their individual effects on the reduction of protein expression of TLR4/MyD88/NF-κB pathway were not consistent. However, their combination could significantly reduce all parameters of this inflammatory pathway as compared to untreated I/R rats ( p < 0.001). Therefore, the combined treatment with GMc1 and DNL increased the potency of each intervention in protecting the aged hearts against I/R injury. Reduction in the activity of the TLR4/MyD88/NF-κB signaling pathway and subsequent modulation of the activity of inflammatory cytokines and endogenous antioxidants play an important role in this cardioprotection.


2021 ◽  
Author(s):  
Pullaiah Chitikela P ◽  
Vinod K Nelson ◽  
Sushma R ◽  
Narasimha Kumar GV ◽  
Thyagaraju K

Abstract BackgroundEsculetin is a natural coumarin derivative from various plants with multiple pharmacological effects. Hence, the present study was undertaken to explore the cardio protective potential of esculetin against isoproterenol induced myocardial toxicity in rats. Methods The treatment schedule was fixed for 28 days and the rats were divided into five groups of six each. Rats of group I received the normal saline and served as normal control, group II was received ISO (100mg/kg body weight) for last two consecutive days of the study and served as disease control. Groups III and IV received esculetin 10 and 20 mg/kg body weight respectively once a day per oral for 28 days along with ISO for last two consecutive days of the study. Cardiac biomarkers such as CK-MB and LDH, membrane bound Na+ /K+ ATPases activity, myocardial lysosomal enzymes activity and tissue antioxidants status were estimated in the heart tissue samples. The histopathological changes in the myocardium were also assessed. Further, DPPH assay was done to evaluate the free radicals scavenging potential of esculetin. Cytoxicity assay, intracellular ROS levels by DCFDA assay and m-RNA expression of TNF-α, IL-6 and NF-κB by quantitative RT-PCR in H9c2 cell lines.ResultsThe increased levels of CK-MB, LDH, LPO, myocardial lysosomal enzymes and membrane bound Na+ /K+ ATPase levels by ISO administration was significantly increased with concomitant decrease in tissue antioxidant enzymes such as GSH, Catalase, and SOD. Pre-treatment with esculetin for 28 days has significantly decreased the levels of cardiac bio-markers, lysosomal enzymes, membrane bound Na+ /K+ ATPase levels as well as Lipid peroxides which is in contrary to the ISO group. Amelioration of the antioxidant levels were also found in esculetin treated groups. Histopathological examination of heart reveals that myocardial degeneration, mononuclear cell infiltration was noticed in ISO treated rats, whereas the same was restored with esculetin treatment. In H9C2 cell lines esculetin could effectively reduced intracellular ROS inhibition and m-RNA expression of pro-inflammatory cytokines including TNF-α, IL-6 and NF-κB to prevent apoptosis or cell necrosis. Conclusion The study provides the evidence of cardioprotective potentials of esculetin against isoproterenol induced myocardial infarction by antioxidant and myocardial membrane stabilization along with in vitro protection from arsenic induced ROS cell necrosis or apoptosis in H9C2 cells.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Nakanishi ◽  
K Kaikita ◽  
M Ishii ◽  
Y Oimatsu ◽  
T Mitsuse ◽  
...  

Abstract Background Rivaroxaban, a direct activated factor X (FXa) inhibitor, has been established for prevention and treatment of arterial and venous thrombosis. Although FXa plays an important role in thrombosis, FXa also involves in inflammation via the protease-activated receptor (PAR)-1 and PAR-2 pathway. We assessed the hypothesis that rivaroxaban might protect cardiac remodeling after myocardial infarction (MI) in mice. Methods MI was induced in wild-type mice by permanent ligation of the left anterior descending coronary artery. At 1 day after MI, mice were randomly assigned to the rivaroxaban and vehicle groups. In the rivaroxaban group, the mice were provided with regular chow diet including rivaroxaban (2400ppm) after the randomization. We evaluated the cardiac function by echocardiography, expression of mRNA and protein in the infarcted and non-infarcted area 7 days after MI. Furthermore, we measured infarct size, infiltration of inflammatory cells by pathological analysis 7 days after MI. Results The fractional shortening (%FS) and Interventricular Septal thickness in diastole (IVSTd) was significantly improved 7 days after MI in the rivaroxaban group compared with the vehicle group (%FS, p=0.01; IVSTd, p=0.013). As for pathological analysis, rivaroxaban decreased infarct size (p=0.026) and the number of infiltrated macrophages in the non-infarcted area (p=0.011) compared with vehicle. The mRNA expression in tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β in the infarcted area and atrial natriuretic peptide (ANP) in the non-infarcted area was significantly lower in the rivaroxaban group compared with the vehicle (TNF-α, p=0.015; TGF-β, p=0.019; ANP, p=0.012). PAR-1 and PAR-2 mRNA expression in the infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (PAR-1, p=0.005; PAR-2, p=0.037). Furthermore, western blot analysis demonstrated that the phosphorylation of Extracellular Signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) in the non-infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (ERK, p=0.015; JNK, p=0.002). Conclusions The present study showed that rivaroxaban protected against cardiac dysfunction, probably due to the suppression of PAR-mediated increase of pro-inflammatory cytokines post-MI. Rivaroxaban might be potentially effective for improving the cardiac remodeling after MI. Acknowledgement/Funding This study was supported in part by trust-research grant from Bayer Yakuhin, Ltd.


Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 39
Author(s):  
Sahar Youssef ◽  
Marwa Salah

Olanzapine is an antipsychotic drug effective in the treatment of stress-associated psychiatric illnesses, but its effect on the spleen remains unclear. Vitamin C is essential for the optimum function of the immune system. We aim to investigate the effect of Olanzapine on spleen structures and to assess the protective effect of vitamin C. Forty adult male albino rats were divided into four groups: group (I), a control; group (II), rats were given vitamin C at 40 mg/kg body weight; group (III), rats were given Olanzapine at 2 mg/kg body weight; and group (IV), rats were given vitamin C and Olanzapine at the same dose of group (II) and group (III) for one month. The hematoxylin and eosin (H&E) of the olanzapine treated group showed focal areas of cellular depletion and a decrease in the size of the white pulp. The red pulp was expanded and showed marked congestion and dilatation of blood sinusoids. Cluster of differentiation 3 (CD3) was significantly reduced, however both tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were significantly higher. The administration of vitamin C repaired structural and immunohistochemical changes via increased CD3 and decreased TNF-α and VEGF. Therefore, the oxidative and the inflammatory pathways may be the possible mechanisms underlying olanzapine immunotoxicity. Vitamin C exerted immune modulator and antioxidant effects against olanzapine.


2016 ◽  
Vol 48 (2) ◽  
pp. 578-582 ◽  
Author(s):  
L. García-Covarrubias ◽  
C. Pliego ◽  
L. Bermudez ◽  
A. Cicero ◽  
J. Cancino ◽  
...  

1980 ◽  
Vol 37 (12) ◽  
pp. 2266-2271 ◽  
Author(s):  
Donald R. Gunderson

Theory on r-K selection is used as a basis for examining correlations between instantaneous rate of natural mortality (M), gonad-body weight index, age at maturity, longevity, and Bertalanffy growth parameters (k, L∞) for 10 species of marine fish. All correlations were consistent with r-K selection theory. The gonad-body weight index was found to be more highly correlated with M than any of the other life history parameters examined (r2 = 0.62), and stepwise multiple regression showed that additional variables added little to the predictive ability of the model. The gonad-body weight index appears to be quite useful in predicting M, and development of an analogous index on an energetics basis might enhance its utility in this regard.Key words: natural mortality, r-K selection, life history parameters


Author(s):  
Amir Reza Karamibonari

Introdution: Crataegus oxycanta (hawthorn) is used in herbal and homeopathic medicine as a cardiotonic.The present study was done to investigate the effect of the Crataegus oxycanta on antioxidant status in induced myocardial infarction in rat. Methods: In this experimental study, four groups of wistar rats (200-220g) each comprising 10 animals, were selected for this study. Group I, rats served as control. Group II rats were given isoperternol (85mg/kg body weight) subcutaneously on 15th and 16th days. Group III rats were given Crataegus oxycanta (100mg/kg/day), orally for 30 days.  Group IV rats were given Crataegus oxycanta (100mg/kg/day), orally for 30 days and isoperternol (85mg/kg body weight, subcutaneously) was given on 15th and 16th days. At the end of the experimental period, the rats were anaesthetized and blood obtained from the heart then rats were sacrificed and the hearts were removed for biochemical and histological analysis. The activity of malondialdehyde (MDA), catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidants was studied. Descriptive one-way analysis of variance (ANOVA) was used in different group. Significance was defined as P ≤ 0.05. Statistical analysis was performed using SPSS software version 16. Results: Crataegus significantly reduced plasma and heart tissue MDA levels (p<0.05) and significantly increased catalase, SOD, GPX and total antioxidant levels versus the group that received only isoperternol (p<0.05 ). Crataegus also decreased the rate of edema, inflammatory cell infiltration and heart tissue necrosis compared to the group that received only isoperternol. Conclusion: The study confirms the protective effect of Crataegus oxycanta against tissue damage and  oxidative stress caused by  isoperternol induced myocardial infarction


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