Cardiotoxic (Arrhythmogenic) Effects of 1,1-Difluoroethane Due to Electrolyte Imbalance and Cardiomyocyte Damage.

Inhalant abuse is the intentional inhalation of chemical vapors to attain euphoric effects. Many common household products are abused by inhalation and one is 1,1-difluoroethane (DFE), which is a halogenated hydrocarbon used in refrigeration, dust-off spray, and airbrush painting. Although many human DFE abuse cases have been studied, the etiology and mechanism of sudden death is still unknown. In this study, an animal model was used to simulate the human conditions of DFE inhalation abuse that results in sudden death.Current research targets mechanistic studies involving electrolyte changes and cardiomyocyte damage after DFE administration in vivo. To investigate these changes, Sprague Dawley rats (N = 6) were exposed to 30 seconds of 20 L/min of DFE in multiple doses. Isoflurane acted as a control. Two additional groups, epinephrine and epinephrine + DFE, were included to simulate the clinical condition of DFE abuse. Plasma sodium, potassium, calcium, and magnesium levels were measured, followed by lactate dehydrogenase, creatine kinase, and cardiac troponin I levels. In addition, oxidative stress markers were also evaluated in all animal groups. Electrolyte levels showed a significant rise in plasma potassium and magnesium levels for the treated groups. In addition, lactate dehydrogenase, creatine kinase, and cardiac troponin I levels in DFE and epinephrine + DFE administered rats were significantly elevated as compared with control. Some oxidative stress makers were also elevated significantly in treatment groups. Furthermore, histopathological analysis showed hyperemia/congestion in treated rats.These results support cardiotoxic effects indicating that DFE results in fatal arrhythmias, and the study can be important during clinical cases involving inhalant abuse.

Structure elucidation and inhibitory effects on human platelet aggregation of chlorogenic acid from Wrightia tinctoria.

BACKGROUND: Interest in natural compounds as sources of potentially new treatment options is growing rapidly. Preliminary screening of many different plant extracts showed that Wrightia tinctoria acts as a potent human platelet aggregation inhibitor. The aim of the present study was to isolate and characterize the active compound responsible for potent inhibition of human platelet aggregation in vitro. METHODS: A 70% ethanolic extract derived from W. tinctoria seeds was fractionated with chloroform followed by ethyl acetate. The ethyl acetate fraction was further fractionated and purified through a series of three successive column chromatographic separations using silica gel, Sephadex LH-20, and C-18 columns. Liquid chromatography coupled to negative electrospray ionization tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) studies were performed in the structure determination of the active phenolic compound present in the ethyl acetate fraction of W. tinctoria seeds. RESULTS: A phenolic compound has been isolated and identified as chlorogenic acid by LC-MS/MS and NMR studies. Chlorogenic acid showed concentration-dependent inhibitory effect on collagen-induced platelet aggregation in vitro with an IC50 of 0.2363 µg/µl. CONCLUSION: The present data suggest that chlorogenic acid can be developed as potential antiplatelet agent in the treatment of cardiovascular diseases in diabetes mellitus.

The effects of taurine and thiotaurine on oxidative stress in the aorta and heart of diabetic rats.

This study has compared the actions of the sulfur-containing compounds taurine (TAU) and thiotaurine (TTAU) with those of insulin (INS) on the oxidative stress that develops in the aorta and heart as a result of diabetes. Diabetes was induced in male Sprague-Dawley rats with streptozotocin (60 mg/kg, i.p.). Starting on day 15, and continuing for the next 41 days, the diabetic rats received each day 2 mL of physiological saline or 2.4 mmol/kg/2 mL of TAU (or TTAU) p.o. or 4 U/kg of isophane INS s.c. Normal rats served as controls. The rats were sacrificed on day 57 to collect blood, heart and thoracic aorta samples. Untreated diabetic rats exhibited a lower body weight gain (by 34%), higher than normal plasma glucose (by ∼4-fold), cholesterol (by 66%) and triglycerides (by 188%) levels, and lower INS levels (by 76%). Also there was a marked increase in catalase activity (≥90%); and clear decreases in nitrite (≥40%), glutathione redox status (≥67%), and glutathione peroxidase (≥66%) and superoxide dismutase (≥51%) activities in both the aorta and heart. With only a few isolated instances (plasma lipids), TTAU was either markedly more effective (plasma glucose, plasma INS, aorta and heart glutathione, aorta redox status, and antioxidant enzymes) or marginally more effective (heart redox status) than TAU in attenuating the alterations brought about by diabetes. These results suggest that replacing the sulfonic acid group of TAU by thiosulfonic acid can lead to a greater potency against diabetes-related biochemical changes in the plasma, heart and aorta. However, except for effects on plasma lipids, these sulfur-containing compounds were less effective than INS in counteracting diabetes-related changes.

Effect of Wrightia tinctoria and Parthenocissus quinquefolia on blood glucose and insulin levels in the Zucker diabetic rat model.

The aim of this study is to evaluate the antidiabetic activity of two Indian Ayurvedic herbs using an oral glucose tolerance test and blood insulin levels to understand the mechanism of action using the Zucker diabetic rat model. Herbal extracts of Wrightia tinctoria and Parthenocissus quinquefolia at a dose of (250 mg/kg body weight) were used throughout the study. Following a glucose challenge of 2 gm/kg using oral gavage, a timed glucose tolerance test was used to determine the ability of these extracts to alter glucose levels in diabetic animal model. The glucose lowering activities of these extracts were then compared to the controls. Both tested herbal extracts have shown to exhibit significant (P < 0.05) hypoglycemic activity compared to the control. W. tinctoria and P. quinquefolia have an antidiabetic activity which reduced the blood glucose level in oral glucose tolerance test significantly compared with the control. To further understand their mechanism of action, blood insulin levels were also studied using an insulin Elisa assay. These studies revealed that the herbal extract of P. quinquefolia has direct correlation between glucose and insulin levels. However, W. tinctoria significantly lowered blood glucose levels (P< 0.05), while it did not show any correlation between blood glucose and insulin levels. Based on these findings, it can be concluded that hypoglycemic effects of W. tinctoria are more complicated than P. quinquefolia, and may involve other possible mechanism of action.

Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.

1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in products designed for dusting electronic equipment and air brush painting. When abused, inhaled DFE produces intoxication and loss of muscular coordination. To investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic exposure during abuse, a protocol which has not been conducted. Tissue collection (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120, 240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart 338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38, 0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively. All animals showed signs of intoxication within 20 s manifested as lethargy, prostration and loss of righting reflex. Marked intoxication continued for about 4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8 min, animals continued to show signs of sedation as evidenced by reduced aggression and excitement during handling. No discernable intoxication was evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg, respectively. Plots of concentration (log) versus time were consistent with a two compartment model. Initial distribution was rapid with average half life (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood, 110 s in brain and 168 s in heart. Late elimination half lives were longer with blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1), and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may underestimate these parameters if DFE is abused chronically due to continued uptake into lowly perfused tissues with repeated dosing.

Alpha-glucosidase inhibitory activity of Syzygium cumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats.

Syzygium cumini seed kernel extracts were evaluated for the inhibition of alpha-glucosidase from mammalian (rat intestine), bacterial (Bacillus stearothermophilus), and yeast (Saccharomyces cerevisiae, baker's yeast). In vitro studies using the mammalian alpha-glucosidase from rat intestine showed the extracts to be more effective in inhibiting maltase when compared to the acarbose control. Since acarbose is inactive against both the bacterial and the yeast enzymes, the extracts were compared to 1-deoxynojirimycin. We found all extracts to be more potent against alpha-glucosidase derived from B. stearothermophilus than that against the enzymes from either baker's yeast or rat intestine. In an in vivo study using Goto-Kakizaki (GK) rats, the acetone extract was found to be a potent inhibitor of alpha-glucosidase hydrolysis of maltose when compared to untreated control animals. Therefore, these results point to the inhibition of alpha-glucosidase as a possible mechanism by which this herb acts as an anti-diabetic agent.