Lauro Figueroa-Valverde

Synthesis and evaluation of the cardiovascular effects of two, membrane impermeant, macromolecular complexes of dextran-testosterone

The incidence of cardiovascular disease is greater in men than in premenopausal women. Testosterone has been considered a significant risk factor for cardiovascular disease, but testosterones mechanism of action and its cellular site of action are still not clear. However, it is likely that non-genomic extracellular effects of the hormone are involved. With the aim of providing further information about this phenomenon, two membrane impermeant, macromolecular complexes of testosterone were synthesized and their cardiovascular effects were evaluated. We covalently bound testosterone (through carbon 3 or C-17 functional groups) to dextran (2 MDa) and evaluated its effects on isolated and perfused rat hearts (Langerdorff model). Our results showed that the macromolecular complexes increased vascular resistance similarly to free testosterone and blocked adenosine-induced vasodilatation. These effects were exerted rapidly and possibly through a non-genomic mechanism. Blockade of C-3 or C-17 functional groups by binding to macromolecular dextran induced no qualitative and/or quantitative changes in testosterone-induced effects.

Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats.

AIM The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model. METHODS The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used. RESULTS The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative. CONCLUSIONS The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

Effect of progesterone-carbachol derivative on perfusion pressure and coronary resistance in isolated rat heart: via activation of the M2 muscarinic receptor.

AIM The present study was designed to investigate the effects of progesterone-carbachol derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved. METHODS The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after progesterone-carbachol derivative alone and after the following compounds; mifepristone (progesterone receptor blocker), yohimbine (α2 adreno-receptor antagonist), ICI 118,551 (selective β2 receptor blocker), atropine (non-selective muscarinic receptor antagonist), methoctramine (antagonist of M2 receptor) and L-NAME (inhibitor of nitric oxide synthase). RESULTS The results show that progesterone-carbachol derivative [10(-9) mM] significantly decreased perfusion pressure (P=0.005) and coronary resistance (P=0.006) in isolated rat heart. Additionally, the effect of progesterone-carbachol on perfusion pressure [10(-9) to 10(-4) mM] was only blocked in the presence of methoctramine and L-NAME. CONCLUSIONS These data suggest that progesterone derivative exert its effect on perfusion pressure via activation of the M2 muscarinic. In addition, this phenomenon involves stimulation of nitric oxide synthase (NOS).

Biological activity exerted by omega-3 fatty acids on body mass index, glucose, total cholesterol and blood pressure in obese children

Background: Obesity is risk factor to development cardiovascular diseases. There are several studies which indicate that fatty acids can exert changes in body fat in children. However, the results found relatively are few and have generally been conducted over short time periods with small sample sizes, making it difficult to draw definitive conclusions. Objective: In this study the effect induced by omega-3 fatty acids on some biological parameters such as glucose, total cholesterol and body mass index levels in obese children were evaluated. Methods: A dietary intake of gummies with omega-3 fatty acids at dose (100-350 mg) was administered to obese children. Then, glucose, total cholesterol and body mass index levels were determinate using an apparatus (accutrend pluss) and enzyme-immunoassay techniques. Results: The results showed that dietary intake of gummies with omega-3 fatty acids induces significantly changes on total cholesterol and body mass index levels in obese girls compared with obese boys. Conclusions: All these data suggest that dietary intakes of omega-3 fatty acids could be used for the treatment of degree of obesity in obese girls. However, it is important to mention that it is also necessary to evaluate the beneficial effect of omega-3 fatty acids on other biological parameters involved in the degree of obesity as well as the possible toxicity involved in its administration. great controversy about the effect exerted by intake dietary of omega-3 fatty acids against obesity. Therefore, in this study the effect produced by omega-3 fatty acids on some factors associated with obesity such as glucose, body mass index, total cholesterol, and blood pressure levels was evaluated on obese children. Material and Methods Fifth and sixth graders (n=300) in two San Francisco de Campeche Mexico schools were invited to participate in a dietary intake gummy with omega-3 fatty acids at dose of 100 to 350 mg. The parents were informed about the nature and the purpose of this study, and a consent form was signed by parents. In addition, the protocol of this research was previously approved by the ethical committee at the University Autonomous of Campeche. Correspondence to: Lauro Figueroa-Valverde, Laboratory of PharmacoChemistry at the Faculty of Chemical Biological Sciences of the University Autonomous of Campeche, Av. Agustín Melgar s/n, Col Buenavista C.P.24039 Campeche Cam., México, E-mail: lauro_1999@yahoo.com Received: January 31, 2018; Accepted: February 28, 2018; Published: March 05, 2018 García-Cervera E (2018) Biological activity exerted by omega-3 fatty acids on body mass index, glucose, total cholesterol and blood pressure in obese children Integr Obesity Diabetes, 2018 doi: 10.15761/IOD.1000199 Volume 4(1): 2-4 Anthropometric measures Body mass index. Subjects were weighed without shoes. Standing height was measured without shoes to the nearest 0.5 cm with the use of a commercial stadiometer. Body mass index (BMI) was calculated by dividing weight (kg) by height squared (m2). Blood Parameters Measured. A fasting blood sample was obtained for determination of glucose, triglyceride and total cholesterol concentrations were determined using Accutrend Pluss (Hoffmann-La Roche, Grenzach-Wyhlen, Germany) [19]. Evaluation of insulin levels. Insulin assay was performed by enzyme-immunoassay (Human Insulin ELISA kit, Sigma-Aldrich company) according to the manufacturer’s instruction [20]. Statistical analysis The obtained values are expressed as average ± SE [21]. Results Evaluation of Body Mass Index Body Mass Index (BMI) differences in BMI levels for obese boys after of a dietary intake from gummies with omega-3 fatty acids at a dose of 100 mg (31.00 ± 1.2 Kg/m2), 150 mg (30.04 ± 1.2 Kg/m2), 200 mg (29.00 ± 1.2 Kg/m2), 210 mg (29.29 ± 1.2 Kg/m2), 280 (28.13 ± 1.2 Kg/m2) and 350 mg (25.00 ± 1.7 Kg/m2) in comparison with control (31.48 ± 1.7 Kg/m2). Other results indicate that an intake from gummies with omega-3 fatty acids in obese girls at different doses 100 mg (29.00 ± 1.2 Kg/m2), 150 mg (28.50 ± 1.2 Kg/m2), 200 mg (28.00 ± 1.2 Kg/m2), 210 mg (28.71 ± 1.2 Kg/m2), 280 (27.57 ± 1.2 Kg/m2) and 350 mg (24.00 ± 1.7 Kg/m2) exert changes on BMI levels compared with control (30.40 ± 1.8 Kg/m2). Determination of Glucose levels Administration of dietary intake from gummies with omega-3 fatty acids to obese boys at dose of 100 (102.00 ± 1.7 dg/ml), 150 (110.00 ± 1.7 dg/ml), 200 (115.02 ± 1.7 dg/ml), 210 mg (98.04 ± 1.7 dg/ml), 280 mg (102.00 ± 1.3 dg/ml) and 350 mg (108.00 ± 1.4 dg/ml) was no significant differences. Also, the dietary intake with omega-3 fatty acids in obese girls at dose of 100 (98.00 ± 1.6 dg/ml), 150 (100.00 ± 1.4 dg/ ml), 200 (104.02 ± 1.5 dg/ml), 210 mg (110.00 ± 1.6), 280 mg (107.00 ± 1.3) and 350 mg(102.16 ± 1.2 ) was no significantly changes in the glucose levels compared control conditions (100 .02 ± 1.6). Evaluation of insulin levels The data found showed that insulin levels was not significantly difference in obese boys after of a dietary intake of gummies with omega-3 fatty acids at dose of 100 (14.00 ± 1.5 μU/L), 150 (14.40 ± 1.4 μU/L), 200 (14.60 ± 1.5 μU/L), 2 10 mg (14.80 ± 1.2 μU/L), 280 mg (14.88 ± 1.3 μU/L) and 350 mg (14.08 ± 1.2 μU/L) compared with conditions control (14.0800 ± 1.4 μU/L). Additionally, other results showed that dietary intake of gummies with omega-3 fatty acids in obese girls at doses of 100 (14.50 ± 1.4 μU/L), 150 (14.88 ± 1.3 μU/L), 200 (14.00 ± 1.5 μU/L), 210 mg (13.98 ± 1.1 μU/L), 280 mg (14.20 ± 1.5 μU/L) and 350 mg (14.88 ± 1.4 μU/L) was no significant differences compared with control (13.88 ± 1.5 μU/L). Cholesterol total The results showed significantly variations in cholesterol total levels for obese boys after of a dietary intake of gummies with omega-3 fatty acids at dose of 100 (202.00 ± 1.6 mg/dl), 150 (194 ± 1.5 mg/dl), 200 (190.00 ± 1.7 mg/dl), 210 mg (188.14 ± 1.6 mg/dl), 280 mg (172.12 ± 1.8 mg/dl) and 350 mg (152.10 ± 1.9 mg/dl) in comparison with obese boys without treatment. Other data showed in the Figure 2 indicated that dietary intake with omega-3 fatty acids in obese girls at dose of 100 (186.00 ± 1.6 mg/dl), 150 (182.00 ± 1.5 mg/dl), 200 (180.00 ± 1.7 mg/dl), 210 mg (176.00 ± 1.6 mg/dl), 280 mg (170.00 ± 1.6 mg/dl) and 350 mg (144.10 ± 1.9 mg/dl) exert changes on cholesterol total levels compared with conditions control (188.75 ± 1.5 mg/dl). Blood pressure On the other hand, other results from a dietary intake of gummies with omega-3 fatty acids in obese boys showed significant changes on blood pressure at dose of 100 mg (114.00 mg/dl ± 12.0), 150 mg (108.00 mg/dl ± 14.0), 200 mg (116.00 mg/dl ± 17.0) 210 mg (114.20 mg/dl ± 15.0), 280 mg (118.02 mg/dl ± 13.0) and 350 mg (110.200 mg/dl ± 14.0) with relation to control (116.00 mg/dl ± 13.0). Finally, other data showed that dietary intake with omega-3 fatty acids in obese girls at dose of 100 (106.00 ± 1.4 mg/dl), 150 (104.00 ± 1.4 mg/dl), 200 (102.00 ± 1.7 mg/dl), 210 mg (99.00 ± 1.4 mg/dl), 280 mg (102.00 ± 1.5 mg/dl) and 350 mg (102.04 ± 1.6 mg/dl) produce changes on blood pressure compared with conditions control (112.02 ± 1.4 mg/dl). Discussion There are some reports which indicate that obesity is a factor risks to development several cardiovascular diseases [2,3]. To reduce this clinical pathology some strategies have been used; for example, an intake dietary with high-fiber [22], fruit and vegetable [23] or use of drugs such as Orlistat, sibutiramine, rimonabant and others; however, some of these treatment may produce some adverse effects [24]. Evaluation of effect produced by omega-3 fatty acids on Body Mass Index (BMI) In the search of some therapeutic alternative to reduce the obesity, the effect exerted by a dietary intake of gummies with omega-3 fatty acids on some parameters clinical such as body mass index glucose, cholesterol and blood pressure in an obese children population was evaluated. The results showed that effect produced by a dietary intake of gummies with omega-3 fatty acids decreased BMI levels in obese girls compared to obese boys and control (obese girls without treatment) at different doses (Figure 1); these data are supported by some studies previously reported [25], which indicate that administration of omega-3 fatty acids decreased the BMI in obese girls. Determination of biological activity exerted by omega-3 fatty acids on Cholesterol total concentration Analyzing the data above mentioned and other studies which suggest that intake diet of n-3 polyunsaturated fatty acids can produce changes on total cholesterol levels [26], in this study, the effect exerted by omega-3 fatty acids on total cholesterol concentration in obese children was evaluated. The results found indicated that omega-3 fatty acids significantly reduce the total cholesterol concentration in obese girls compared with obese boys and controls (Figure 2). However, it is noteworthy that some studies indicate that omega-3 fatty acids, in addition of alterations of total cholesterol also may exert changes in blood pressure levels [27]. Evaluation of effect produced by omega-3 fatty acids on Blood Pressure In this study, the biological activity of by dietary intake of gummies with omega-3 fatty acids on blood pressure in obese children was García-Cervera E (2018) Biological activity exerted by omega-3 fatty acids on body mass index, glucose, total cholesterol and blood pressure in obese children Integr Obesity Diabetes, 2018 doi: 10.15761/IOD.1000199 Volume 4(1): 3-4 evaluated. The results showed (Figure 3) that omega-3 fatty acids decreased the blood pressure in a dependent-dose manner compared with obese boys and controls (obese children, without treatment). These data are similar to other studies that indicate that omega-3 fatty acids can induce changes in blood pressure in hypertensive patients [28]. It is important to mention that this phenomenon also may also be conditioned by changes