Evaluation of the effect of Exercise Trainings and CGRP receptor antagonist (BIBN 4096) on mitochondrial dynamic in the hippocampus of male Wistar rats.

BACKGROUND: Exercise training showed beneficial effects on brain. The purpose of the present study is to evaluate the effect of six weeks of high-intensity interval training (HIIT) and Endurance training (ET) with calcitonin gene-related peptide (CGRP) receptor antagonist on the expression of genes involved in mitochondrial dynamics and apoptosis in hippocampal tissue of male Wistar rats. METHODS: In this study, forty-two healthymale Wistar rats (8-week) were randomly divided into 6 groups (n = 7) as follow; 1) Control; 2) HIIT which performed 6 weeks of HIIT; 3) ET which performed 6 weeks of endurance training; 4) CGRPi received 10 mg/kg CGRP receptor antagonist every day at the last 2 weeks; 5) CGRPi-HIIT performed HIIT and received CGRP receptor antagonist; 6) CGRPi-ET performed ET and received CGRP receptor antagonist. Real-time PCR (2-ΔΔCT) and western blotting were employedto measure the expression of genes and protein, respectively. RESULTS: HIIT and ET significantly increased Bcl-2, Pgc-1α, Sirt3, and Nrf-1 gene expression in the hippocampal tissue (p < 0.05, p < 0.01, p < 0.01, and p < 0.001, respectively). ET-CGRPi and HIIT-CGRPi significantly increased Sirt3, Pgc-1α, and Nrf-1 gene expression compared to the control group (p < 0.05, p < 0.01, and p < 0.05, respectively). CONCLUSION: ET and HIIT-induced physiological alterations in the hippocampus. In fact, this modulation showed protective properties in the hippocampusvia up regulation of Bcl-2, Pgc-1α, Nrf-1, and Sirt3 gene expression. CGRPi did not cause gene or protein changes harmful to mitochondrial dynamic balance and apoptosis in the hippocampus of rats.

Effect of Pistacia Atlantica Resin Oil on Anti-Oxidant, Hydroxyprolin and VEGF Changes in Experimentally-Induced Skin Burn in Rat.

BACKGROUND: Severe burn damage and its consequences are life threatening which can complicate patients' health. Medicinal and traditional plants are considered as safe, natural and inexpensive source of treatment for wide variety of diseases. This study assessed beneficial effect of Pistacia atlantica oil on rats burn wound healing and its potential effects on malondialdehyde (MDA), vasculoendothelial growth factor (VEGF), hydroxyprolin and antioxidant status in wound area. METHODS: Thirty male rats weighing 200±10 g were randomly divided into three groups (n=10) as follows. Group 1 underwent just burn injury, Group 2 underwent burn injury and received 150 mg/kg/day P. atlantica oil topically, and Group 3 underwent burn injury and received 150 mg/kg/day sulfadiazine cream topically. At the end of the study (day 14), wounded areas were measured and then skin in the burn damage were dissected and anti-oxidative parameter, MDA, VEGF and hydroxyprolin were evaluated. RESULTS: P. Atlantica oil significantly increased antioxidant defense, VEGF, hydroxyprolin and reduced MDA levels. It could remarkably reduce wound size compared to burn control group. P. Atlantica oil showed more beneficial effects than sulfadiazine. CONCLUSION: P. atlantica resin oil could be considered as a new therapeutic agent for treatment of injuries.

The effect of different digoxin concentrations on heart tissue and antioxidant status in iron-overloaded rats.

BACKGROUND: Thalassaemia is a hereditary disorder and has an economic burden on patients and the government. The most prevalent complication in these patients is iron overload which is followed by cardiomyopathy. Digoxin is considered as a treatment against heart failure in thalassaemia. The present study evaluated the effect of two digoxin concentrations on iron content and antioxidative defense in cardiac tissue of iron-overloaded rats. METHODS: The study was conducted on 48 rats which were divided into 6 groups. Group 1 was the control group and did not receive any treatment and group 2 was the iron overload group. In addition groups 3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS) were assessed in cardiac tissues. RESULTS: Co-administration of iron-dextran and digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P < 0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron overload groups. GPX levels significantly reduced in groups 5 and 6 (iron + digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron control group. CONCLUSION: Digoxin remarkably facilitates iron uptake by cardiomyocytes by affecting other channels such as L-type and T-type Ca2+ channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model deteriorated antioxidative parameters and increased iron entry into heart tissue at higher doses. Therefore, in patients with beta thalassaemia major, digoxin must be administered with great care and serum iron and ferritin must be regularly monitored.

B12 and Folate Concentrations in Opium Addicts Compared to Healthy Subjects: A Case Control Study from Kerman Coronary Artery Disease Risk Study.

BACKGROUND: Opium addiction is a global problem which has implicated many societies. Opium addiction and drug abuse is related to harmful consequences which affect life style, biochemical factors, and vitamins values, and also is considered as a risk for heart diseases. Folate and B12 levels are related to homocysteine and studies about their levels in opium addicts are controversial; therefore, we designed this study to evaluate B12 and folate values in opium addicts. METHODS: From the Kerman Coronary Artery Disease Risk Study (KERCADRS) which is a population-based study, we randomly selected 340 men and entered them into two groups: case (n = 170) and control group (n = 170). Then vitamin B12 and folate levels were measured. FINDINGS: Opium addiction did not change B12 and folate levels significantly in opium addicts compared to non-addict control subjects. However, only some variables including blood pressure (BP) and diabetes positively and cigarette smoking, triglyceride (TG), alcohol, and cardiovascular disease (CVD) history negatively affected folate, and none of clinical and demographic variables influenced the B12 levels (P > 0.050). TG had significant effects on B12 and folate levels although opium addiction did not show any impact. CONCLUSION: High TG levels were accompanied by low levels of B12 and folate. Reduced B12 and folate values are accompanied by serum homocysteine elevation. As TG elevates in opium addicts, it can be considered as an important factor which affects vitamins levels and reduces their absorption. Opium addiction elevates homocysteine level, since we can conclude that homocysteine elevation in opium addicts is independent of B12 and folate levels.

Ameliorative Effects of Endurance Exercise with Two Different Intensities on Nandrolone Decanoate-Induced Neurodegeneration in Rats: Involving Redox and Apoptotic Systems.

Despite the importance of this issue, less has been paid to the influence of exercise on the neural side effects of anabolic androgenic steroids and mechanisms. We investigated the effects of two levels of endurance exercise on neurodegeneration side effects of nandrolone. The study period was 8 weeks. Wistar rats were divided into nine groups including the control (CTL) group, mild exercise (mEx) group, and vehicle (Arach) group which received arachis oil intramuscularly, nandrolone (Nan) group which received nandrolone decanoate 5 mg/kg two times weekly, mEx+Arach group which treated with arachis oil along with mild exercise, mEx+Nan group which treated with nandrolone along with mild exercise, severe exercise (sEx) group, sEx+Arach, and sEx+Nan groups. Finally, brain samples were taken for histopathological, biochemical, and western blot analysis. Nandrolone significantly decreased the intact cells of the hippocampus, total antioxidant capacity (TAC) (P < 0.05 versus CTL and Arach groups), TAC to malondialdehyde ratio (TAC/MDA), and Bcl-2. Nandrolone increased the Bax/Bcl-2 ratio of the brain tissue (P < 0.01 versus CTL and Arach groups). Combination of mild exercise and nandrolone rescued the intact cells to some extent, and this effect was associated with the improvement of Bcl-2 level and Bax/Bcl-2 ratio of brain tissue. Combination of severe exercise and nandrolone rescued the intact cells and improved the TAC, TAC/MDA, and Bax/Bcl-2 ratios. The findings suggest that low- and high-intensity endurance exercise decreased the risk of neurodegeneration effect of nandrolone in the hippocampus of rats. This effect can be explained by the regulation of the redox system and cell homeostasis.

miR-33 inhibition attenuates the effect of liver X receptor agonist T0901317 on expression of liver X receptor alpha in mice liver.

BACKGROUND: microRNAs play pivotal roles in metabolism and other aspects of cell biology. microRNA-33 and liver X receptor (LXR) affect lipid metabolism and cholesterol trafficking. In this study, we evaluated effects of co-administration of miR-33 inhibitor and LXR activator on LXR-α and adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression in mice liver. METHODS: Twenty-four mice were randomly allocated into four groups (n = 6). Group 1 mice received standard chow diet without any treatment, group 2 received 30 mg/kg/48 hour LXR agonist (T0901317), group 3 received 1 mg/kg/48 hour in vivo locked nucleic acids (LNA) anti-miR-33 and group 4 received both T0901317 and in vivo LNA anti-miR-33. All treatments were administrated through intraperitoneal injection (IP). After 7 days and at the end of the study, mice were sacrificed, liver tissues were excised and blood samples were collected. LXR-α and ABCA1 genes and protein expression were quantified by real-time polymerase chain reaction (PCR) and western blotting, respectively. RESULTS: LXR activation caused LXR-α and ABCA1 mRNA (P < 0.050) and protein elevation as compared to control (P < 0.001). miR-33 inhibition attenuates T0901317 effect on LXR-α expression in group IV. Co-administration of T0901317 and anti-miR-33 remarkably elevated high-density lipoprotein cholesterol (HDL-C) levels, compared to control group (P = 0.001). Separate administration of T0901317 and anti-miR-33 also elevated HDL-C levels (P < 0.010). CONCLUSION: Co-administration of T0901317 and anti-miR-33 can be considered as a good therapeutic alternative for atherosclerosis because miR-33 inhibition reduced lipogenic effects of LXR-α activator and also helps LXR-α agonist to increase reverse cholesterol transport (RCT) and also HDL-C as antiatherogenic effects.

Effects of digoxin on cardiac iron content in rat model of iron overload.

BACKGROUND: Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca2+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood. METHODS: We assessed the effect of different concentrations of digoxin on cardiac iron content in rat model of iron overload. Digoxin had been administrated intraperitoneally (IP) for one week before main study began to assure increased digoxin levels. Group 1 received four IP injections of iron-dextran (12.5mg/100g body weight) every 5 days evenly distributed over 20 days. Groups 2-4 received 0.5, 1 and 5 mg/kg/day IP digoxin, respectively. Last three groups 5-7 received iron-dextran as group 1 and digoxin concentrations 0.5, 1 and 5 mg/kg/day, respectively. RESULTS: Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (0.5, 1 and 5 mg/kg/day) of digoxin than their counterparts in control groups and this pattern was also observed in pathology assessment. CONCLUSION: It seems that digoxin plays an important role in iron transport into heart in iron overload state but exact mechanism of this phenomenon is not clear. L-type Ca2+ channels are good candidates that probably could be involved in iron accumulation in cardiomyocytes. Thus it would be better to reconsider digoxin administration in thalassemia and iron overload conditions.

The effect of opium addiction on serum adiponectin and leptin levels in male subjects: a case control study from Kerman Coronary Artery Disease Risk Factors Study (KERCADRS).

OBJECTIVES: Serum adiponectin and leptin levels have been shown to be related to obesity, insulin resistance and cardiovascular diseases (CVD). Opium addiction has a positive association with endocrine system disorders. The relationship between adipokines and opium addiction is unclear. In the present study, we aimed to determine serum adiponectin and leptin levels in opium addicted subjects. METHODS: 176 men, 88 opium addicts and 88 non- addicts were randomly selected from subjects who participated in Kerman Coronary Artery Disease Risk factors Study (KERCADRS); a population-based study. Serum adiponectin and leptin levels were measured using ELISA and compared between two groups. We adjusted the effect of some confounding factors such as the patients' demographic, clinical and medical history in multivariate analysis model. RESULTS: The serum level of adiponectin in opium addicts was significantly lower than control group (6.5±3.6 vs. 9.8±8.1 µg/ml, P<0.001). There was no significant difference in serum leptin level between two groups (11.8±10.3 ng/ml in control group vs. 11.5±10.8 ng/ml in opium addicts, p = 0.80). In the multivariate analysis, after adjusting for age, cigarette smoking, body mass index, type 2 diabetes, hypertension, cholesterol, triglyceride and high and low density lipoproteins, the negative association between opium addiction and decreased adiponectin level was still present (ß = -0.144, P value = 0.005). CONCLUSIONS: The results showed that opium addiction reduces serum adiponectin level. Since adiponectin has been shown to have anti-diabetic and anti-atherogenic effects, its reduction may account for increase in the risk of metabolic disorders such as insulin resistance and CVD amongst opium addicted patients.

Ameliorative effect of black tea on nicotine induced cardiovascular pathogenesis in rat.

Regarding the role of nicotine in the development of cardiovascular complications of smoking, we investigated whether black tea has a modulatory effect on cardiovascular pathogenesis of nicotine in rat. Animals were randomized to control, tea, nicotine and tea plus nicotine groups. Test groups received black tea brewed (adding 400 ml boiling water to 10 g Lipton black tea for 5 min) orally alone or with nicotine 2 mg/kg/day, s.c. separately or combined for four weeks. On 28th day, lipids profile of blood and also malondialdehyde (MDA) level, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) of heart tissue were measured. Nicotine administration caused a significant increase in total cholesterol, TG and HDL-C and also atherogenic index of plasma (log TG/HDL-C). Moreover, nicotine increased MDA level of heart. Black tea alone increased the antioxidant capacity of heart tissue without significant effect on lipid profile and MDA levels. Concomitant use of black tea and nicotine significantly attenuated the hyperlipidemic and atherogenic effects of nicotine but was unable to attenuate the MDA. Our findings suggest that black tea consumption reduces hyperlipidemia and atherogenesis as two cardiovascular risk factors and complications of nicotine, in rat. If these results can be extrapolated to human, smokers who daily drink black tea may be less at risk of cardiovascular disease.