Evaluation of the Effects of High Intensity Interval Training on Cytokine Levels and Clinical Course in Treatment of Opioid Use Disorder. / Opioid Kullanim BozukluguTedavisinde Yüksek Yogunluklu Aralikli Egzersizin Sitokin Düzeyleri ve Klinik Seyir Üzerine Etkileri.

OBJECTIVE: Opioid use disorder (OpUD) is a biological and psychosocial disorder with limited treatment options. Addition of physical exercise to the pharmacological treatment has been proposed to be effective on reducing substance use and improving the quality of life. In this study we aimed to investigate the effects of a high-intensity interval training (HIIT) program on the serum levels of cortisol, insulin-like growth factor1 (IGF-1), interferon-gamma (IFN-γ), interleukin 17 (IL-17) and the clinical progress of inpatients with OpUD. METHOD: Our study enrolled 22 male inpatients diagnosed with OpUD on the basis of the DSM-5 criteria. Two groups of 11 individuals were formed as the exercise (EG) and the control (CG) groups. The EG conducted 5 sessions of a HIIT. Participant data were collected with Sociodemographic Questionnaire, the Addiction Profile Index (API), and the Barratt Impulsiveness Scale (BIS-11). Also, the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A) and the Substance Craving Scale (SCS) were used before and after the treatment program in order to evaluate the clinical progress. Blood samples were collected on the 5th and the 21st days for estimation of the serum cortisol, IGF-1, IFN-γ and the IL-17 levels. RESULTS: Comparison of the pre- and the post- treatment performances of the two groups on the HAM-D, the HAM-A and the SCS indicated a significant drop in the respective scores of the EG. Also, a significant increase was observed in the post-treatment IGF-1 level of the EG as compared to the CG. No differences were observed between the cortisol, IFN-γ and IL-17 levels of the EG and the CG. CONCLUSION: HIIT resulted in significant reduction in the symptoms of depression, anxiety and substance craving, and increased the serum IGF-1 levels. HIIT did not change serum cortisol, IFN-γ and IL-17 levels. We believe this research will contribute to the literature on the treatment of opioid depencence by emphasising the effects of HIIT on patients treated for OpUD.

The Effects of Irisin on Nω-Nitro-L-arginine Methyl Ester Hydrochloride-Induced Hypertension in Rats

Background: The cause of about 95% of hypertension, an important public health problem, is unknown. Intensive studies are underway to understand the physiopathology of hypertension. Irisin, a newly discovered hormone, has been reported to dilate vascular smooth muscle and lower blood pressure acutely. Aims: To investigate the effects of chronic irisin treatment on blood pressure and renal functions in a hypertension model established by nitric oxide synthase inhibition by treatment with Nω-nitro-L-arginine methyl ester hydrochloride. Study Design: Animal experimentation. Methods: Male Sprague−Dawley rats were divided into four groups (n=8). Control and irisin groups received an intravenous saline injection, hypertension and hypertension + irisin (hypertension + irisin) groups received 1.5 mg/100 g Nω-nitro-L-arginine methyl ester hydrochloride. Nω-nitro-L-arginine methyl ester hydrochloride (150 mg/L) was added to the drinking water of rats in groups hypertension and hypertension + irisin for three weeks. In the second week of the experiment, irisin (50 nmol/day) was given to rats in groups irisin and hypertension + irisin, and saline was administered to rats in groups control and hypertension for two weeks through subcutaneously placed osmotic minipumps. Blood pressure was measured by the tail-cuff plethysmography method. On the twenty-first day of the experiment, 24-hour urine, blood, and both kidneys of the rats were collected. Results: The hypertension group had elevated systolic, diastolic, and mean arterial blood pressure values compared with the control group, with decreased glutathione levels in tissue and serum, but an increase in serum oxidized glutathione level (p<0.05). Histopathologically, increased tubular injury, cast formation, glomerular sclerosis, and peritubular fibrosis levels were observed (p<0.05). Irisin treatment did not cause any significant change in blood pressure, renal functions, and injury scores. However, renal nitric oxide levels significantly increased, and endothelial nitric oxide synthase immunoreactivity was determined to be reduced (p<0.05). Conclusion: Treatment with chronic irisin at a physiological dose does not reduce blood pressure in an experimental model of hypertension. In different models of experimental hypertension, the effects of irisin administration at different doses and at different periods should be thoroughly investigated.

Alteration in cardiac PI3K/Akt/mTOR and ERK signaling pathways with the use of growth hormone and swimming, and the roles of miR21 and miR133.

Athletes misuse recombinant human growth hormone (r-hGH) to enhance their performance. Although r-hGH is known to increase cardiac hypertrophy, the underlying molecular mechanism remains unclear. The aim of the present study was to investigate the role of r-hGH in cardiac intracellular signaling pathways and of miR-21 and miR-133 expression in rat hearts during exercise. A total of 36 adult male Sprague-Dawley rats were divided into sedentary control (SC, n=9), swimming exercise (SE, n=8), r-hGH (GH, n=10) and swimming exercise plus r-hGH (SE-GH, n=9) groups. The exercise groups completed a 1-h swimming exercise 5 times a week for 8 weeks. Subcutaneous r-hGH was administered as 0.3 mg/kg/day. Phosphoinositide-3-kinase (PI3K), serine/threonine protein kinase 1 (AKT1), extracellular signal-regulated kinase (ERK), microRNA (miR)-21 and miR-133 expression was evaluated in ventricular muscle by real-time quantitative polymerase chain reaction. Protein expression of PI3K, AKT1, ERK and mechanistic target of rapamycin (mTOR) was also assessed by immunohistochemistry. Statistical differences were analyzed by two-way ANOVA. PI3K and AKT1 expression and the gene and protein levels was notably increased in the SE-GH group compared with in SC ventricular tissues (P<0.05). mTOR protein expression was higher in the GH, SE and SE-GH groups compared with in the SC group (P<0.05, <0.05 and <0.001, respectively). ERK gene/protein expression was similar across all groups. miR-21 and miR-133 levels in ventricular muscle were higher in the SE and GH groups than those in the SC group. In summary, growth hormone application coupled with swimming exercise appeared to affect the PI3K/AKT/mTOR signaling pathway in the left ventricular tissue of rats; however, ERK signaling pathway appeared inactive in physiological left ventricular hypertrophy caused by swimming and GH administration over 8 weeks. Furthermore, GH treatment resulted in increased miR-21 and miR-133 expression. Future study by our group will aim to assess the effects of higher dose GH treatment.