BackgroundAn area of ongoing controversy is the role adenosine to regulate vascular tone in conduit vessels that regulate compliance, and the role of nitric oxide (NO), potassium channels and receptor subtypes involved. The aim of our study was to investigate adenosine relaxation in rat thoracic aortic rings, and the effect of inhibitors of NO, prostanoids, Kv, KATP channels, and A2a and A2b receptors.MethodsAortic rings were freshly harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, 11 mM glucose, pH 7.4, 37 °C. Isolated rings were pre-contracted sub-maximally with 0.3 μM norepinephrine (NE), and the effect of increasing concentrations of adenosine (1 to 1000 μM) were examined. The drugs L-NAME, indomethacin, 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined in intact and denuded rings. Rings were tested for viability after each experiment.ResultsAdenosine induced a dose-dependent, triphasic relaxation response, and the mechanical removal of the endothelium significantly deceased adenosine relaxation above 10 μM. Interestingly, endothelial removal significantly decreased the responsiveness (defined as % relaxation per μM adenosine) by two-thirds between 10 and 100 μM, but not in the lower (1–10 μM) or higher (>100 μM) ranges. In intact rings, L-NAME significantly reduced relaxation, but not indomethacin. Antagonists of voltage-dependent Kv (4-AP), sarcolemma KATP (glibenclamide) and mitochondrial KATP channels (5-HD) led to significant reductions in relaxation in both intact and denuded rings, with ouabain having little or no effect. Adenosine-induced relaxation appeared to involve the A2a receptor, but not the A2b subtype.ConclusionsIt was concluded that adenosine relaxation in NE-precontracted rat aortic rings was triphasic and endothelium-dependent above 10 μM, and relaxation involved endothelial nitric oxide (not prostanoids) and a complex interplay between smooth muscle A2a subtype and voltage-dependent Kv, SarcKATP and MitoKATP channels. The possible in vivo significance of the regulation of arterial compliance to left ventricular function coupling is discussed.

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Background. Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. Objective. This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and Methods. Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. Results. The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p<0.05). The average blood pH was 7.36 ± 0.02 and base excess was −5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p<0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion. Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.

Introduction: Antituberculosis drugs are associated with hepatic and renal toxicities due to drug’s radical metabolites. Kleinhovia hospita L extract possesses a potent antioxidant capacity that can be beneficial in eradication of oxidative-induced cell damage. This study aimed to evaluate the effects of K. hospita hydro-alcoholic extract on biomarkers and structure changes in liver and kidney induced by a combination of antituberculosis drugs (CAD), comprising isoniazid, rifampicin, pyrazinamide and ethambutol in Wistar rats. Methods: Thirty-five male Wistar rats were assigned into one of the five groups: control, CAD, and CAD with K. hospita extract in three different doses (125, 250 and 500 mg/kg). The extract was administered three hours prior to CAD and all treatments were carried out for 28 days. Following the last day of treatment, blood samples and organs were collected for biomarker analysis and histopathological examinations. Results: Twenty-eight days of CAD treatment in rats induced marked elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum creatinine and urea levels compared to controls. K. hospita extract at higher doses (250 mg/kg and 500 mg/kg) significantly improved ALT, urea and creatinine levels in the rats treated with CAD (P<0.05), although it did not significantly reduce AST. Furthermore, liver and renal tissue damages induced by CAD were restored with K. hospita extract treatment, especially at higher doses. Conclusion: Kleinhovia hospita extract treatment has the potential to protect the liver and renal damage induced by toxic doses of CAD.

Background Cycling is a physical exercise that is widely performed to improve physical fitness. Regular physical exercise will lead to adaptations to exercise. This adaptation is useful in suppressing the production of reactive oxygen stress (ROS) generated in response to cellular metabolism that uses oxygen. Transforming growth factor beta-1 (TGF-β1) plays a role in increasing the production of ROS, thus, when the concentration is low, it would lead to an improvement in physical fitness. This study aims to compare levels of TGF-β1 between recreational cyclists and sedentary groups. In addition, this research also compares several other parameters, which are fasting blood sugar levels and lipid profiles (triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol) between cyclists and sedentaries. Methods This was an observational analytical study with a cross-sectional design. The research subjects consisted of 2 groups, each consisting of 21 participants, namely the recreational cyclist and the sedentary group. Anthropometric examinations were carried out, including body weight, height, body mass index, waist circumference, and body fat percentage. Fasting blood glucose concentration and lipid profile (Triglyceride – TG , Total Cholesterol – Total C , HDL Cholesterol – HDL-C , and LDL Cholesterol – LDL-C ) were determined by the enzymatic colorimetric methods, and TGF-β1 levels were determined using the fluorescence of specific antibodies for TGF-β1 (pg/ml) using ELISA method. Statistical analysis was performed using IBM SPSS v. 25. Results The anthropometric variables, other than body height, did not differ significantly between the two groups, so did the fasting blood glucose concentration. Nevertheless, the lipid profile (TG, Total C, HDL-C and LDL-C) were found to be significantly better in the cyclist group (p < 0.05). The mean level of TGF-β1 in recreational cyclists was 8, 908.48 pg/ml, lower than the control group, 10, 229.28 pg/ml. The results of the unpaired t -test showed significant mean differences between the two groups, (p = 0.001; p < 0.05). Conclusion The levels of TGF-β1 in the recreational cyclist group were lower than the sedentary group. Regular physical exercise will trigger exercise adaptations that can suppress latent TGF-β1 activation.