ATP releasing channels and the ameliorative effects of high intensity interval training on diabetic heart: a multifaceted analysis.

Type 2 diabetes (T2D) can cause severe cardiac complications at functional, histologic and molecular levels. These pathological complications could be mediated by ATP-releasing channels such as Panx1 and ATP receptors, in particular P2X7. The aim of our study was to investigate the effect of high-intensity interval training (HIIT) on T2D-induced cardiac complications at the functional, histopathological and molecular levels, with a particular focus on ATP-releasing channels. 48 male Wistar rats at the age of 8 weeks were randomly allocated into four groups: control (Con), Diabetes (T2D), Training (TR), and Diabetes + Training (T2D + TR). T2D was induced by a high-fat diet plus a low dose (35 mg/kg) of STZ administration. Rats in the TR and T2D + TR groups underwent an 8-weeks training program involving intervals ranging from 80 to 100% of their maximum running speed (Vmax), with 4-10 intervals per session. Protein expression of Interleukin 1ß (IL1ß), Interleukin 10 (IL-10), Pannexin 1 (Panx1), P2X7R (purinergic P2X receptor 7), NLRP1 (NLR Family Pyrin Domain Containing 1), BAX, and Bcl2 were measured in the heart tissue. Additionally, we assessed heart function, histopathological changes, as well as insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). In contrast to the T2D group, HIIT led to increased protein expression of Bcl2 and IL-10 in the heart. It also resulted in improvements in systolic and diastolic blood pressures, heart rate, ± dp/dt (maximum and minimum changes in left ventricular pressure), while reducing protein expression of IL-1ß, Panx1, P2X7R, NLRP1, and BAX levels in the heart. Furthermore, left ventricular diastolic pressure (LVDP) was reduced (P ≤ 0.05). Moreover, heart lesion scores increased with T2D but decreased with HIIT, along with a reduction in fibrosis percentage (P ≤ 0.05). The results of this study suggest that the cardioprotective effects of HIIT on the diabetic heart may be mediated by the modulation of ATP-releasing channels. This modulation may lead to a reduction in inflammation and apoptosis, improve cardiac function, and attenuate cardiac injury and fibrosis.

Exercise Training Attenuates Cardiac Vulnerability and Promotes Cardiac Resistance to Isoproterenol-Induced Injury Following Hookah Smoke Inhalation in Male Rats: Role of Klotho and Sirtuins.

Hookah smoking is on the rise around the world. Present study investigated the heart resistance to harmful stress following long-term waterpipe tobacco smoking (WTS) and moderate-intensity exercise training intervention in male Wistar rats. Animals were randomly divided into a non-ischemic heart control group and four ischemic heart groups including ISO (isoproterenol-treated), Ex + ISO (subjected to exercise plus ISO), S + ISO (exposed to hookah smoke plus ISO), and Ex + S + ISO (subjected to exercise along with hookah smoke plus ISO). After eight weeks of training and WTS, heart ischemia induced by isoproterenol injections. Then, cardiac functional indices and some biochemical and histopathological parameters were assessed. WTS + ISO reduced systolic pressure, ± dP/dt max, and contractility indices (P < 0.001 vs. ISO group) and increased end diastolic pressure and Tau index (P < 0.001 vs. ISO) of the left ventricle. Also, WTS + ISO was associated with an increase in Bax protein level and Bax/Bcl-2 ratio (P < 0.05 and P < 001, respectively, vs. ISO group) as apoptotic markers of heart tissue. Hookah smoke significantly decreased SIRT1 (P < 0.05 and P < 0.001, respectively, vs. ISO) and klotho (P < 0.01 and P < 0.001, respectively, vs. ISO) in serum and heart, and SIRT3 and pS9-GSK-3ß (P < 001 and P < 0.05, respectively, vs. ISO) in heart tissue. Combination of exercise with WTS prevented the hookah smoke-induced alterations in apoptotic markers, cardiac functional indices, and SIRT1, SIRT3, klotho, and pS9-GSK-3ß proteins. The findings demonstrated that hookah smoke inhalation intensifies ventricular dysfunction and decreases heart resistance to harmful stresses. Moderate-intensity exercise training attenuated these complications partly through recovering the klotho and sirtuins levels and apoptosis-survival balancing.

Involvement of Sirtuins and Klotho in Cardioprotective Effects of Exercise Training Against Waterpipe Tobacco Smoking-Induced Heart Dysfunction.

Despite its negative effect on the cardiovascular system, waterpipe smoking (WPS) is currently popular worldwide, especially among youth. This study investigated the effects of moderate endurance exercise on heart function of rats exposed to WPS and its possible mechanism. The animals were randomly divided into four groups: control group (CTL), the exercise group (Ex) which trained for 8 weeks, the waterpipe tobacco smoking group (S) exposed to smoke inhalation (30 min per day, 5 days each week, for 8 weeks), and the group that did exercise training and received waterpipe tobacco smoke inhalation together (Ex + S). One day after the last session of Ex and WPS, cardiac pressures and functional indices were recorded and calculated. The levels of SIRT1, SIRT3, Klotho, Bax, and Bcl-2 in the serum and heart, the expression of phosphorylated GSK3ß of heart tissue, and cardiac histopathological changes were assessed. WPS reduced systolic pressure, +dP/dt max, -dP/dt max, and heart contractility indices (P < 0.001 vs. CTL) and increased cardiac tissue lesions (P < 0.05 vs. CTL) and end diastolic pressure and Tau index (P < 0.001 vs. CTL) of the left ventricle. Exercise training normalized the left ventricular end diastolic pressure, +dP/dt max, and contractility index. Also, exercise improved the levels of SIRT1, SIRT3, Klotho, and Bcl-2 and reduced Bax level in the heart. The findings showed that WPS causes left ventricular dysfunction. Moderate exercise prevented WPS-induced heart dysfunction partly through its anti-apoptotic features and activation of the sirtuins and Klotho pathways.

Exposure to GSM 900-MHz mobile radiation impaired inhibitory avoidance memory consolidation in rat: Involvements of opioidergic and nitrergic systems.

The use of mobile phones is increasing, and the main health concern is the possible deleterious effects of radiation on brain functioning. The present study aimed to examine the effects of exposure to a global system for mobile communication (GSM) with mobile phones on inhibitory avoidance (IA) memory performance as well as the involvement of endogenous opioids and nitric oxide (NO) in this task. Male Wistar rats, 10-12 weeks old, were used. The results showed that four weeks of mobile phone exposure impaired IA memory performance in rats. The results also revealed that post-training, but not pre-training, as well as pre-test intracerebroventricular (i.c.v.) injections of naloxone (0.4, 4 and 40 ng/rat), dose-dependently recovered the impairment of IA memory performance induced by GSM radiation. Additionally, the impairment of IA memory performance was completely recovered in the exposed animals with post-training treatment of naloxone (40 ng/rat) plus pre-test i.c.v. injections of L-arginine (100 and 200 nmol/rat). However, pre-test i.c.v. injections of L-NAME (10 and 20 nmol/rat), impaired IA memory performance in the animals receiving post-training naloxone (40 ng/rat). In the animals receiving post-training naloxone treatment, the impairment of IA memory performance due to pre-test i.c.v. injections of L-NAME was recovered by the pre-test co-administration of L-arginine. It was concluded that the recovery from impairment of IA memory in GSM-exposed animals with post-training naloxone treatment was the result of blockade of the opioidergic system in early memory consolidation as well as activation of the nitrergic system in the retrieval phase of memory.

Protective effects of Echium amoenum Fisch. and C.A. Mey. against cerebral ischemia in the rats.

BACKGROUND: This study was designed to evaluate the protective effect of Echium amoenum total anthocyanin extract (ETAE) on partial/transient cerebral ischemia in the rats. MATERIALS AND METHODS: Rats received ETAE (50, 100 and 200 mg/kg, i.p.) 30 min before the induction of cerebral ischemia. Cerebral ischemia was induced by bilateral common carotid arteries occlusion (BCCAO) for 30 min, followed by 72 h reperfusion. The neurological deficit, brain performance, and sensory motor function were assessed 48 h and 72 h after surgery. After sacrification, the brains were evaluated for myeloperoxidase (MPO) activity and histopathological changes. RESULTS: Our results showed that motor function significantly decreased in ischemia/reperfusion (I/R) group as compared to the sham group. Histopathological analysis exhibited the shrinkage and atrophy of the neurons in I/R group. ETAE at the dose of 200 mg/kg improved spontaneous activity and memory induced by cerebral ischemia compared to the control group and also decreased brain MPO activity following cerebral ischemia. However, it could not affect the ability to climbing, body proprioception, vibrissae touch and brain water content. In addition, pretreatment with ETAE at higher doses significantly reduced ischemia-induced neuronal loss of the brain. CONCLUSION: The anthocyanin rich fraction from E. amoenum was found to have protective effects against some brain damages postischemic reperfusion. However, further researches are required for investigating the exact mechanisms of the effect of this plant in the prevention of cerebral ischemia in human.

The Validity and Reliability of the Persian Version Test of Mobile Phone Dependency (TMD).

OBJECTIVE: Despite the fact that the mobile phone has become a pervasive technology of our time, little research has been done on mobile dependency. A valid and reliable assessment instrument corresponding to the Persian culture is essential. This study aimed to describe the construction and validation of the Persian version of TMD (Test of Mobile phone Dependency) to assess the addictive use of mobile phone. METHODS: This was a cross- sectional study, for which data were collected from 350 students who were studying at Tehran universities. Sampling method was quota sampling. The participants anonymously completed the demographic questionnaire, and CPDQ as a valid questionnaire and gold standard. Finally, clinical interview [based on DSM-IV-TR] was performed. To analyze the data, concurrent validity, factor analysis, internal consistency (Cronbachα), split half; test-retest and ROC Curve by SPSS18 Software were used. RESULTS: As a result of the reliability analysis and factor analysis by principal component and Varimax rotation, three factors ("salient", "preoccupation" and "Spend a lot of time and money") for both male and female participants were extracted. Internal consistency (Cronbach's alpha) of the TMD was .92 (Cronbach alpha of the factors is .88, .82, and .84, respectively). The test-retest correlation of the TMD was .56.The best cut off point for this questionnaire (TMD) is 38. CONCLUSION: The TMD proved to have an acceptable internal consistency with adequate factor models to assess the extent of problems caused by the "misuse" of the mobile phone in the Iranian society. Therefore, it can be concluded that the Persian version of the test was reliable and valid; however, further analysis is needed. .