Therapeutic effects of the combination of moderate-intensity endurance training and MitoQ supplementation in rats with isoproterenol-induced myocardial injury: The role of mitochondrial fusion, fission, and mitophagy.

INTRODUCTION: Mitochondrial dysfunction causes myocardial disease. This study investigated the effects of MitoQ alone and in combination with moderate-intensity endurance training (EX) on cardiac function and content and mRNA expression of several proteins involved in mitochondrial quality control in isoproterenol (ISO)-induced heart injuries METHODS: Seven groups of CTL, ISO, ISO-EX, ISO-MitoQ-125, ISO-MitoQ-250, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 were assigned. Rats were trained on a treadmill, and the MitoQ groups received MitoQ in drinking water for 8 weeks, starting one week after the induction of heart injury. Arterial pressure and cardiac function indices, mRNA expression, protein content, oxidant and antioxidant markers, fibrosis, and histopathological changes were assessed by physiograph, Real-Time PCR, immunofluorescence, calorimetry, Masson's trichrome, and H&E staining, respectively. RESULTS: The impacts of MitoQ-125, EX+MitoQ-125, and EX+MitoQ-250 on arterial pressure and left ventricular systolic pressure were higher than MitoQ-250 or EX alone. ± dp/dt max were higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-MitoQ-125 and ISO-MitoQ-250 groups, respectively. Histopathological scores and fibrosis decreased in ISO-EX, ISO-MitoQ-125, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 groups. The restoration of MFN2, PINK-1, and FIS-1 changes was higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-EX, ISO-MitoQ-125 and ISO-MitoQ-250 groups. The expression of MFN2 and PINK-1 was lower in ISO-MitoQ-125 and ISO-EX+MitoQ-125 than ISO and CTL groups. The expression of FIS-1 in ISO-EX and ISO-EX+MitoQ-250 increased compared to CTL and ISO groups. MDA decreased in ISO-MitoQ-125 and ISO-EX+MitoQ-125 groups. CONCLUSION: Exercise and MitoQ combination have additive effects on cardiac function by modulating cardiac mitochondria quality. This study provided a possible therapy to treat heart injuries.

Treatment for Myocardial Infarction: In Vivo Evaluation of Curcumin-Loaded PEGylated-GQD Nanoparticles.

ABSTRACT: Curcumin (Cur) has been suggested as a complementary treatment for cardiovascular diseases. Its efficiency, however, is modest due to poor biocompatibility. This study examined the effects of curcumin loaded on polyethylene glycol-graphene quantum dots (Cur-PEG-GQDs) on hemodynamic and cardiac function in rats with myocardial infarction (MI). The study groups included control, MI, MI+Cur-3, MI + Cur-7, MI + Cur-15, MI + PEG-GQDs-5, MI + PEG-GQDs-10, MI + Cur-PEG-GQDs-5, and MI + Cur-PEG-GQDs-10. MI was established by left anterior descending artery ligation. Two weeks after intraperitoneal administration of vehicle, Cur, PEG-GQDs, and Cur-PEG-GQDs, blood pressure and heart contractility indices were measured. Triphenyl tetrazolium chloride, colorimetry, and clinical laboratory methods were used to measure the infarct size, the oxidant and antioxidant content, and the kidney and liver function parameters, respectively. In the MI animals, Cur-7, PEG-GQDs-10, Cur-PEG-GQDs-5, and Cur-PEG-GQDs-10 recovered systolic blood pressure, diastolic blood pressure, left ventricular systolic pressure, and ±dp/dt max disturbances and reduced myocardial infarct size, fibrosis, and left ventricular end-diastolic pressure. Curcumin lowered antioxidant markers and elevated 1 oxidant marker in the heart in a dose-dependent manner. Although Cur-PEG-GQDs-5 and Cur-PEG-GQDs-10 reduced curcumin's oxidative stress effects, the superoxide dismutase, glutathione peroxidase, and total antioxidant capacity levels were significantly lower in Cur-PEG-GQDs-5 and Cur-PEG-GQDs-10 groups compared with the MI group. Malondialdehyde levels were lower in Cur-PEG-GQDs-5 and -10 groups compared with the Cur-3, Cur-7, and Cur-15 groups. The glutathione/glutathione disulfide ratio improved in the groups treated by Cur-7, PEG-GQDs-10, Cur-PEG-GQDs-5, and Cur-PEG-GQDs-10. The findings indicated that Cur-PEG-GQDs mitigated MI-induced cardiac dysfunction. However, because of the increase in oxidative stress in the heart, nonclassic mechanisms may be involved in the beneficial effect of Cur-PEG-GQDs on MI-induced cardiac dysfunction.

Effect of an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. on oxidative stress, memory impairment and withdrawal syndrome induced by morphine.

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats.Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting.Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level.Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.

Trends in the Prevalence and Incidence of Opium Abuse and its Association with Coronary Artery Risk Factors in Adult Population in Iran: Findings from Kerman Coronary Artery Disease Risk Factors Study.

Background: The prevalence of opium addiction in Iran is high probably due to the belief that opium has preventive effects against cardiovascular diseases. In the second phase of Kerman coronary artery disease risk factors study, the prevalence, incidence rate, and the association between opium use and other coronary artery disease risk factors (CADRFs) were assessed. Methods: In a cross-sectional study (2014-2018), 9996 inhabitants of Kerman, southeastern Iran, aged 15-80 years were recruited to the study. After taking fasting blood samples, the participants were examined or interviewed for demographic data and CADRFs, including opium use. The participants were categorized into "never", "occasional", and "dependent" users. The association between opium use and CADRFs was assessed with adjusted regression analysis (Stata v.11 software). Results: The overall prevalence of opium consumption was lower than that of five years earlier (P<0.01). The prevalence was currently higher in men than women and decreased in men between the two phases (P<0.001). There was a positive correlation between opium use and depression (P<0.001), anxiety (P<0.05), and a negative association with the level of physical activity (P<0.001). The five-year incident rate of dependent and occasional opium use was 4.2 and 3.9 persons/100 person-years, respectively. The incidence of opium use was higher in diabetic, hypertensive, depressed, anxious, and obese subjects. Conclusion: The study did not demonstrate any protective effects of opium on CADRFs. Considering the higher rate of opium use in subjects with hypertension, diabetes, obesity, and psychological disorders, the health authorities should implement educational programs to warn and correct the unsafe belief.

The effects of methanolic extract of Glycyrrhiza glabra on the prevention and treatment of bleomycin-induced pulmonary fibrosis in rat: experimental study.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by dyspnea and progressive loss of lung function. In this study, the preventive and therapeutic effects of methanolic extract of Glycyrrhiza glabra on pulmonary fibrosis were investigated. Pulmonary fibrosis was induced by administration of bleomycin (BLM) into the left lung of rats. Methyl-prednisolone (M-pred, 4 mg/kg) and methanolic extract of G. glabra (500 mg/kg) were injected intraperitoneally from the 1st to 14th days in the preventive group and from the 14th to 28th days in the therapeutic group once every day. Pulmonary inflammatory and fibrotic indices were evaluated by hematoxylin and eosin (H&E) and Masson's trichrome, respectively. The level of hydroxyproline as an index of pulmonary fibrosis and malondialdehyde (MDA) as an oxidative stress biomarker and catalase were measured by the related ELISA Kits. Pulmonary inflammatory and fibrotic indices in the G. glabra and M-pred groups significantly reduced compared with BLM group. G. glabra decreased the level of hydroxyproline in pulmonary tissue similar to M-pred. MDA reduced in G. glabra and M-pred groups compared with BLM group. The activity of catalase increased in the G. glabra preventive group. According to the results, G. glabra prevented and treated pulmonary fibrosis and inflammation in rats. Therefore, G. glabra may be suggested for the prevention and treatment of pulmonary fibrosis and inflammation.

Anti-Inflammatory and Anti-Oxidative Effects of Myrtenol in the Rats with Allergic Asthma.

The aim of the present study was to investigate the effect of Myrtenol, the active ingredient of Myrtle on the oxidant and anti-oxidant indices and cytokines in the allergic asthma. Allergic asthma was induced by ovalbumin (OVA) sensitization and inhalation in four groups of rats; Control, Asthma, Asthma + Dexamethasone and Asthma + Myrtenol. Myrtenol (50mg/kg) or Dexamethasone (2.5mg/kg) was administered intraperitoneally for 7 consecutive days after OVA inhalation. At the end, histopathological parameters, and interleukins (Interleukin-10 (IL10), Interferon gamma (IFN-γ) , interleukin-1ß (IL-1ß), Tumor Necrosis Factor α (TNF-α)), and oxidative stress biomarkers, Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the lung and serum were measured by hematoxylin and eosin staining and ELISA method, respectively. Myrtenol reduced the pathological changes in the lungs and airway endothelium (P < 0.01), (P < 0.5). The level of IL-1ß (P < 0.05) and MDA in the serum and lung tissue (P < 0.01), (P < 0.05), and also the level of TNF-α (P < 0.05) in the lung tissue decreased in the Myrtenol group compared to the asthma group. Myrtenol increased the level of IL-10 (P < 0.05) and the activity of GPX in the lung tissue and serum (P < 0.001). Myrtenol may improve asthma by increasing the ratio of antioxidants to oxidants and reducing the ratio of pro-inflammatory to anti-inflammatory interleukins in the lung. Myrtenol is presented as a potent herbal medicine ingredient for the treatment of asthma.