Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training.

BACKGROUND: Type 2 diabetes (T2D) leads to serious respiratory problems. This study investigated the effectiveness of high-intensity interval training (HIIT) on T2D-induced lung injuries at histopathological and molecular levels. METHODS: Forty-eight male Wistar rats were randomly allocated into control (CTL), Diabetes (Db), exercise (Ex), and Diabetes + exercise (Db + Ex) groups. T2D was induced by a high-fat diet plus (35 mg/kg) of streptozotocin (STZ) administration. Rats in Ex and Db + Ex performed HIIT for eight weeks. Tumor necrosis factor-alpha (TNFα), Interleukin 10 (IL-10), BAX, Bcl2, Lecithin, Sphingomyelin (SPM) and Surfactant protein D (SPD) levels were measured in the bronchoalveolar lavage fluid (BALF) and malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured in lung tissue. Lung histopathological alterations were assessed by using H&E and trichrome mason staining. RESULTS: Diabetes was significantly associated with imbalance in pro/anti-inflammatory, pro/anti-apoptosis and redox systems, and reduced the SPD, lecithin sphingomyelin and alveolar number. Performing HIIT by diabetic animals increased Bcl2 (P < 0.05) and IL10 (P < 0.01) levels as well as surfactants components and TAC (P < 0.05) but decreased fasting blood glucose (P < 0.001), TNFα (P < 0.05), BAX (P < 0.05) and BAX/Bcl2 (P < 0.001) levels as well as MDA (P < 0.01) and MDA/TAC (P < 0.01) compared to the diabetic group. Furthermore, lung injury and fibrosis scores were increased by T2D and recovered in presence of HIIT. CONCLUSION: These findings suggested that the attenuating effect of HIIT on diabetic lung injury mediated by reducing blood sugar, inflammation, oxidative stress, and apoptosis as well as improving pulmonary surfactants components.

A review on plants and herbal components with antiarrhythmic activities and their interaction with current cardiac drugs.

This paper aimed to compile information on plants or their compounds which have experimentally shown antiarrhythmic effect and to scrutinize the efficacy and potency of them and their potential interaction with conventional cardiac drugs. Literature searches were accomplished by using numerous electronic databases, and the available knowledge on different parts of herbs and their ingredients with antiarrhythmic effects up to 2019 were identified and collected. The results indicate that 36 herbs or their derivatives can be effective in the treatment of arrhythmias, especially in animal and cellular models. They affect various ionic channels in different action potential phases. The alterations in ionic currents lead to changing in the amplitude and duration of the action potential, effective refractory period, maximum velocity, resting membrane potential, channel trafficking, or intracellular calcium concentration. The agents that prolong action potential duration and effective refractory period such as dauricine and sophocarpine seem to be more beneficial if more comprehensive studies confirm their efficacy and safety. It is noteworthy that the consumption of some herbal agents for cardiovascular (e.g. Hawthorn and Ginseng) or other (e.g. Ginseng and Licorice) therapeutic purposes may boost the pro-arrhythmogenic effect of current cardiovascular drugs such as cardiac glycosides. This study accentuates known plants or their derivatives with anti-arrhythmic effects, potential interaction with other cardiac drugs, and the possible mechanisms involved. It can assist clinicians and scientists in research and therapeutic approaches to the management of cardiac arrhythmias.

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers.

CONTEXT: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system. OBJECTIVE: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats. MATERIAL AND METHODS: Animals were randomized into control, kernel extract (100 and 200 mg/kg/d, orally), dexamethasone (0.03 mg/kg/d, subcutaneously), dexamethasone + kernel (100 and 200 mg/kg/d, separately), and dexamethasone + captopril (25 mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX). RESULTS: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128 ± 7 vs. 105 ± 3 mmHg, p < 0.05 and 0.2 ± 0.046 vs. 0.08 ± 0.02, p < 0.05). Combination of dexamethasone and walnut (200 mg/kg) prevented the dexamethasone-induced diastolic hypertension (109 ± 3 vs. 128 ± 7 mmHg; p < 0.05), increased the GPX level (14.8 ± 1.46 vs. 5.1 ± 0.64 unit/mg, p < 0.05), reduced the MDA/GPX ratio (0.16 ± 0.015 vs. 0.2 ± 0.046) and improved serum NO level. CONCLUSION: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.

The promising effect of barberry (Zereshk) extract against experimental pulmonary microvascular remodeling and hypertension: A comparison with sildenafil.

CONTEXT: Despite the beneficial effects of barberry (Berberis integerrima Berberidaceae) on decreasing systemic hypertension, its influence has not been investigated on pulmonary hypertension. OBJECTIVE: The objective of this study is to examine the effect of barberry fruit, on monocrotaline-induced pulmonary hypertension. MATERIALS AND METHODS: Nine groups were arranged as follows: the control group, the monocrotaline (M) group, the barberry groups with doses of 50, 100, and 200 (mg/kg), the M plus barberry groups, and the M plus sildenafil group. Two weeks after a single injection of monocrotaline (60 mg/kg, s.c.), barberry water extracts or sildenafil (30 mg/kg/d) were gavaged daily for 2 weeks. At the end of the 4th week, hemodynamic, biochemical, and histopathological parameters were assessed. RESULTS: In comparison with the M group, barberry (200 mg/kg) or sildenafil significantly reduced the right ventricular systolic pressure (RVSP) (22.95 ± 1.78 mm Hg and 30.71 ± 1.64 mm Hg, versus 41.28 ± 1.5 mm Hg), right ventricular hypertrophy (RVH) (0.39 ± 0.03 and 0.42 ± 0.02, versus 0.57 ± 0.02), and the medial wall thickness (MWT) (4.56 ± 0.15 µm and 5.97 ± 0.19 µm, versus 7.02 ± 0.43 µm). Barberry or sildenafil had no significant effect on the plasma level of endothelin-1, glutathione peroxidase, and the malondialdehide of lung. CONCLUSION: 200 mg/kg of barberry has an improving effect on the monocrotaline-induced pulmonary hypertension. This effect was stronger than that of the sildenafil's and may have been mediated through mechanisms other than the modulation of the endothelin-1 or redox system.

The effects of Melissa officinalis (lemon balm) pretreatment on the resistance of the heart to myocardial injury.

CONTEXT: The antihyperlipidemic, antiarrhythmic, neuroprotective and hepatoprotective effects of Melissa officinalis L. (Lamiaceae) have been reported. However, no study has examined its effects on the resistance of the heart to stressful conditions. OBJECTIVE: The objective of this study is to evaluate the effects of aqueous extract of M. officinalis aerial parts on Wistar rat heart with/without cardiac injury. MATERIALS AND METHODS: Animals were grouped as control, isoproterenol (ISO), M. officinalis without (M50, M100, and M200) and with isoproterenol (M50 + ISO, M100 + ISO, and M200 + ISO). The aqueous extract of M. officinalis was orally administered at dosages of 50, 100, and 200 mg/kg/d, respectively, for 7 consecutive days. On the 6th and 7th day, ISO, M50 + ISO, M100 + ISO, and M200 + ISO groups received 85 mg/kg of isoproterenol for myocardial injury induction. On day 8, hemodynamic parameters were recorded and samplings were done. RESULTS: The extract (50, 100, and 200 mg/kg) significantly reduced the heart rate (264 ± 5, 259 ± 5 and 281 ± 3 versus 377 ± 13 in control group, p < 0.01). Blood pressure was significantly decreased in M50 + ISO (75 ± 5) versus M50 (110 ± 6) and M100 + ISO (72 ± 6) versus M100 (105 ± 5 mmHg, p < 0.01). The malondialdehyde levels of the injured hearts were lower in M50 + ISO and M100 + ISO groups than in the ISO group (p < 0.05). Serum cardiac troponin I was higher in the M200 + ISO group (5.1 ± 1.7) than in the ISO group (2.7 ± 0.7 ng/ml, p < 0.05). CONCLUSION: The lower dose of extract, by improving the balance of the redox system and by reducing the heart rate, may increase the heart resistance to injury. However, the higher doses of extract may intensify the injury of ischemic heart.

Potential mechanisms involved in the anticonvulsant effect of walnut extract on pentylenetetrazole-induced seizure.

OBJECTIVE: It was the aim of this study to determine the potential effect of walnut kernel extract (WKE) on experimentally induced seizures in rats and to evaluate the role of benzodiazepines and ethosuximide (ESM) within these pathways. MATERIALS AND METHODS: Male Wistar rats were selected and divided into eight groups. Seizures were evoked by intravenous infusion of pentylenetetrazole (PTZ; 2 mg/ml/min). In combination with PTZ, animals were treated with vehicle or WKE (100 mg/kg i.p.), with or without cotreatment with either flumazenil (FMZ; 5 mg/kg i.p.), ESM (150 mg/kg i.p.) or diazepam (DPZ; 0.5 mg/kg i.p.). RESULTS: WKE administration significantly increased the PTZ dose needed to induce the first myoclonic jerk (13.09 ± 1.29 vs. 49.71 ± 12.03 mg/kg; p < 0.001), decreased the severity of seizure grades and reduced the mortality rate to 0%. FMZ did not significantly reduce the anticonvulsant effect of WKE. The combination of DPZ and WKE showed a synergic anticonvulsant effect, whereas ESM had no significant influence (p > 0.05) on the WKE effects. CONCLUSION: These findings indicated that WKE was effective at reducing seizure severity, at increasing the dose to the first myoclonic jerk and highly efficacious at preventing mortality, because 100% of animals were protected. It seems that this positive effect could apply through signaling pathways other than benzodiazepine-mediated γ-aminobutyric acid receptors and may at least in part be similar to ESM.

Efficacy of Melissa officinalis in suppressing ventricular arrhythmias following ischemia-reperfusion of the heart: a comparison with amiodarone.

OBJECTIVE: We aimed to assess the influence of Melissa officinalis (lemon balm), a well-known herbal drug with numerous applications in traditional and modern medicine, on cardiac conduction and susceptibility to lethal ventricular arrhythmia. MATERIALS AND METHODS: Forty-two male Wistar rats were divided into a control group (CTL), an M. officinalis group that received the aqueous extract of M. officinalis L. intraperitoneally (i.p.) at dosages of 50, 100, 200 and 400 mg/ml/kg, respectively, and an amiodarone group (Amio group) that received 30 mg/ml/kg i.p. of amiodarone. Heart ischemia/reperfusion was induced by the ligation and release of the left anterior descending branch of the left coronary artery. RESULTS: There were no statistical differences between the groups in the basal heart rate and blood pressure. PR, corrected QT (QTc) and QRS intervals increased in the M. officinalis and Amio groups. PR and QTc were statistically significant only in the Amio group and QRS was significant only in the group receiving 400 mg of M. officinalis (M400 group) in comparison with the CTL group. During the reperfusion period, the decrease in ventricular fibrillations was statistically significant in all groups (except the M400 group) when compared with the CTL group. The score of arrhythmia severity also decreased, but was statistically significant only in the Amio group (p < 0.05 vs. CTL group). CONCLUSIONS: Our findings suggest that M. officinalis extract has a mild protective effect against reperfusion-induced lethal ventricular arrhythmias in rats.

Cardioprotective effect of mumie (shilajit) on experimentally induced myocardial injury.

This study assessed the effects of mumie (shilajit) pre-treatment, a traditional drug which is well known in the ancient medicine of both east and west, on cardiac performance of rats subjected to myocardial injury. Animals were divided into control, M250, and M500 (received mumie at dosages of 250 and 500 mg/kg/day, orally for 7 days, respectively) main groups each consisting of two subgroups-with and without heart injury. On the 6th and 7th days, isoproterenol (ISO) (85 mg/kg i.p.) was injected (s.c.) to half of the animal subgroups to induce myocardial damage. On the 8th day, after hemodynamic parameter recordings, hearts were removed for further evaluation. Mumie pre-treatment had no significant effects on hemodynamic and cardiac indices of normal animals. When the cardiac injury was induced, mumie maintained the ±dp/dt maximum, attenuated the serum cardiac troponin I, and reduced the severity of cardiac lesions. Despite the mild positive effects of mumie on total antioxidant capacity and lipid proxidation index, no significant difference was observed among animal groups. The findings suggest the prominent cardioprotective effect of mumie against destructive effects of ISO. It seems that other mechanisms than reinforcements of antioxidant system are involved in this beneficial effect.

Assessment of Safety and Therapeutic Efficacy of Rosa damascena L. and Quercus infectoria on Cardiovascular Performance of Normal and Hyperlipidemic Rabbits: Physiologically Based Approach.

According to the use of Quercus infectoria (QI) and Rosa damascena L. (RD) for therapeutic purposes and lack of adequate information about their cardiovascular effects, we investigated the cardiovascular indices of rabbits which chronically pretreated with these agents. Animal groups were control group (CTL), RD and QI groups with normal chow plus 1.5 g RD and QI extracts, respectively, in each kg of the diet for 45 days; Hyperlipidemic (H) group received high-fat diet for 45 days; H+RD and H+QI groups received high fat diet plus QI and RD extracts, respectively. Blood pressure was greater in H+RD group than CTL, RD, and H groups. Left ventricular developed pressure and left ventricular systolic pressure increased significantly in H+RD group versus CTL and RD groups (P < 0.05 and P < 0.0001, resp.) and in H+QI groups (P < 0.01 versus QI groups). Left ventricular end diastolic pressure (LVEDP) showed significant reduction in H+QI group versus H group. QI attenuated the values of total cholesterol, LDL, TG, and atherogenic indices of plasma when coadministrated with a high-fat diet. The results suggest the antilipidemic and antiatherogenic effects of QI. In addition, the use of RD along with a high-fat diet may increase the risk of hypertension in rabbits.

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: a potential anti-arrhythmic agent.

CONTEXT: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations. OBJECTIVE: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat. MATERIALS AND METHODS: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200 mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30 mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery. RESULTS: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p < 0.05). Ventricular tachycardia (VT)/VF numbers (3.2 ± 1.2), durations (4.9 ± 2.6) and also arrhythmia severity (1.9 ± 0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4 ± 11.6, 52 ± 31 and 3.3 ± 0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p < 0.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval. CONCLUSION: The results suggest that pretreatment with saffron, especially at the dosage of 100 mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.

Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury

The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect (AU)

Combination of opium smoking and hypercholesterolemia augments susceptibility for lethal cardiac arrhythmia and atherogenesis in rabbit.

Opium consumption is increasing in some eastern societies, where it is grown. We investigated the effect of opium smoking on plasma atherogenic index and incidence of lethal cardiac arrhythmia, i.e. ventricular tachycardia (VT) and ventricular fibrillation (VF) in rabbits. Animals were divided into two-, normo- and hyper-cholesterolemic main groups fed with normal or high cholesterol diet prior and during short-term and long-term exposure to opium smoke. Then, isoproterenol (3mg/kg, i.p.) was injected to induce cardiac ischemia and animals were followed for 3h for counting of lethal arrhythmia incidence. Long-term opium smoking significantly increased the plasma atherogenic index. In ischemic hearts, opium smoking along with hypercholesterolemia significantly enhanced the incidence of fatal arrhythmia. This vulnerability was not mediated by changes in QT interval. These data suggest that opium smoking, especially in hypercholesterolemic conditions, can be a predisposing factor for atherogenesis and lethal arrhythmia.

Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury.

The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect.

The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction.

This study was designed to assess the effects of saffron (Crocus sativus) on rats' heart with isoproterenol-induced myocardial injury. Animals were divided randomly into four groups: vehicle-control group (CTL); ISO group, administrated with Isoproterenol 85 mg/kg s.c.; saffron group; and finally combined Saffron + ISO group. Basal and final serum levels of heart troponin I, heart tissue antioxidants and histopathological indices were assessed in all groups. Isoproterenol administration significantly increased serum level of troponin I when compared to control group (3.46 +/- 0.77 vs. 0.53 +/- 0.35 ml in ng/ml, P < 0.001) and reduced significantly the glutathione peroxidase activity of heart muscle (1.63 +/- 0.21 vs. 4.01 +/- 0.64 nmol/mg protein, P < 0.05). The grade of heart muscle damages was severe in more than 70% of ISO group animals. Saffron + ISO group showed remarkably decreased intensity of tissue destruction and significantly decreased serum levels of heart troponin I, when compared to ISO group (1.25 +/- 0.23 vs. 3.46 +/- 0.77 ng/ml, P < 0.05). The level of glutathione peroxidase activity in Saffron + ISO animals did not have significant decline compared to saffron alone. These results suggest the protective role of saffron on ischemic hearts by biochemical and histopathological findings.

Passive opium smoking does not have beneficial effect on plasma lipids and cardiovascular indices in hypercholesterolemic rabbits with ischemic and non-ischemic hearts.

BACKGROUND: To scientifically test a traditionally belief of some Asian countries residents that opium may prevent or have ameliorating effects on cardiovascular diseases (CVD) we investigated the effect of passive opium smoking (POS) on plasma lipids and some cardiovascular parameters in hypercholesterolemic rabbits with ischemic and non-ischemic hearts. METHODS: 40 rabbits were fed for 2 weeks with cholesterol-enriched diet and divided to control (CTL), short-term opium (SO) and long-term opium (LO) groups. SO and LO groups were exposed to POS for 3 days and 4 weeks respectively. ECG, blood pressure (BP) and left ventricular pressure recorded and serum lipid and cardiac troponin I levels were measured. Isoproterenol (ISO) injected for induction of cardiac ischemia and after 4h the above variables were measured along with cardiac histopathology assessment. RESULTS: HDL cholesterol decreased significantly in LO compared to CTL group (35+/-5 vs 53+/-5mg/dl). Groups treated with ISO showed significantly higher increments in troponin I level (P<0.05) except for LO group and reduction of BP was higher in ISO and SO+ISO groups compared to CTL and SO groups respectively (-38+/-6 vs -23+/-4 and -37+/-11 vs -11+/-3 percent respectively, P<0.05). Reduction in BP was significantly lower in LO+ISO compared to ISO group. Opium exposure caused a trend of increase in blood pressure, LDL cholesterol and ECG disturbances, attenuated ISO induced myonecrosis but augmented tissue congestion and hemorrhage. CONCLUSION: POS can be considered as a CVD risk factor. Opium does not reduce BP or cholesterol level, as is anticipated by its users.