Comparative Effectiveness of Defatted Hypotensive Crude Extract, Ethyl Acetate and Butanolic Fractions of Cassytha filiformis L. on Different Models of Hypertensive Rats

The hypotensive effectiveness of defatted crude ethanolic extract, ethyl acetate and butanolic fractions of Cassytha filiformis L. have been compared on anesthesized prednisone-saline-induced (PN) and Prednisone-saline-LNAME -induced (PNL) hypertensive rats. Extract/fractions were given at the dose of 5 mg/kg each while a group treated by 100 μmol/kg oftempol was used as comparison. Extract/fractions/vehicle were commence in 3 consecutive doses intravenously every one hour interval. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) of the animals were measured (Biopac® MP 150 Data Acquisition System). Data were presented as the percentage changes of those parameters and analyzed by three way ANOVA followed by Duncan’s Multiple Range Test. Results showed that the ethanolic defatted extract and tempol decreased animal SBP, DBP, MAP and HR significantly (p0.1). The average percentage decrease of animal SBP and MAP on PNL rats were higher (p0.1). Repeated dose of all samples tent to decrease animal SBP and HR (p0.1). These results indicated that the hypotensive effectiveness of the defatted ethanolic extract of Cassytha filiformis is better as compared to its ethyl acetate and butanolic fractions and these effects are greater on oxidative stress related hypertensive rats

The Relation between Fructose-Induced Metabolic Syndrome and Altered Renal Haemodynamic and Excretory Function in the Rat

This paper explores the possible relationships between dietary fructose and altered neurohumoral regulation of renal haemodynamic and excretory function in this model of metabolic syndrome. Fructose consumption induces hyperinsulinemia, hypertriglyceridaemia, insulin resistance, and hypertension. The pathogenesis of fructose-induced hypertension is dubious and involves numerous pathways acting both singly and together. In addition, hyperinsulinemia and hypertension contribute significantly to progressive renal disease in fructose-fed rats. Moreover, increased activity of the renin-angiotensin and sympathetic nervous systems leading to downregulation of receptors may be responsible for the blunted vascular sensitivity to angiotensin II and catecholamines, respectively. Various approaches have been suggested to prevent the development of fructose-induced hypertension and/or metabolic alteration. In this paper, we address the role played by the renin-angiotensin and sympathetic nervous systems in the haemodynamic alterations that occur due to prolonged consumption of fructose

Cystathione gamma lyase/hydrogen sulphide pathway up regulation enhances the responsiveness of ?1A and ?1B-adrenoreceptors in the kidney of rats with left ventricular hypertrophy

The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of ?1A and ?1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of ?1A and ?1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione ? synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of ?1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while ?1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of ?1A and ?1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development

Diuretic action of exogenous hydrogen sulfide in spontaneously hypertensive diabetic rats

Purpose: To examine the hypothesis that in hypertensive diabetic rats hydrogen sulphide (H2S) reduces blood pressure through diuretic action in addition to its vasodilating effect.Methods: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were used. SHR were divided into three groups: SHR (II), SHR diabetic (III), and SHR diabetic NaHS-Treated (IV) with a group of WKY (I) rats serving as normotensive nondiabetic control. Diabetes was produced in two SHR groups using intraperitoneal streptozotocin (STZ). One diabetic group received NaHS, a donor of H2S (56 μM/kg i.p.) daily for five weeks. Blood pressure was measured in conscious and anesthetized states in surgically prepared animals. Plasma and urinary H2S levels and electrolytes were measured weekly throughout the 35-day period.Results: SHR and diabetic SHR had higher blood pressure and lower plasma and urinary H2S levels compared to WKY controls (p &lt; 0.05). Moreover, the SHR diabetic group had higher plasma sodium, higher absolute and fractional sodium excretions (p &lt; 0.05) but with similar blood pressure compared to SHR controls. NaHS treatment reduced blood pressure and restored H2S and plasma sodium (p &lt; 0.05) levels. Moreover, SHR diabetic-NaHS treated group had higher urine output and absolute urinary sodium excretion compared to the untreated SHR diabetic group (p &lt; 0.05).Conclusion: These results suggest a possible diuretic effect of exogenous H2S in spontaneously hypertensive diabetic rats.Keywords: Spontaneously hypertensive rats, Diabetes, Hydrogen sulphide, Diuretic, Sodium excretion, Urine outpu

Interaction between nitric oxide and renal α1-adrenoreceptors mediated vasoconstriction in rats with left ventricular hypertrophyin Wistar Kyoto rats

Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of renal alpha(1)-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors are known to have antihypertrophic effects however their impact on responsiveness of renal alpha(1)-adrenoreceptors subtypes is unknown. This study investigated the impact of nitric oxide (NO) and its potential interaction with the responsiveness of renal alpha(1)-adrenoreceptors subtypes to adrenergic stimulation in rats with left ventricular hypertrophy (LVH). This study also explored the impact of NO donor on CSE expression in normal and LVH kidney. LVH was induced using isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L-arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal noradrenaline, phenylephrine and methoxamine responses were determined in the absence and presence of selective alpha(1)-adrenoceptor antagonists, 5- methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of cystathione Upsilon lyase was unaltered in the NO treated LVH rats (LVH-NO) group compared to LVH group. The responsiveness of renal alpha(1A), alpha(1B) and alpha(1D)-adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group. These findings suggest that exogenous NO precursor up-regulated the renal eNOS/NO/cGMP pathway in LVH rats and resulted in augmented alpha(1A), alpha(1B) and alpha(1D) adrenoreceptors responsiveness to the adrenergic agonists. There is a positive interaction between H2S and NO production in normal animals but this interaction appears absent in LVH animals

Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream

During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, anti-pyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery

Modification and Validation of an HPLC Method for Quantification of Piroxicam

Piroxicam is a NSAID that is widely used in the treatment of joint pain and osteoarthritis. The objectives of the study were to modify and validate HPLC method so as to obtain an accurate, sensitive and precise method to quantify piroxicam concentrations without interference from the other ingredients presence in the formulation. The method published by Owen et al. was adapted and modified to suit the above requirements. The modification was carried out on the mobile phase as the mobile phase used by the authors was not able to separate the drug peak from the interference of the formulation excipients. The modified mobile phase consisted of 5 mM of disodium hydrogen phosphate adjusted to pH 3 with concentrated ortho phosphoric acid, methanol, acetonitrile and glacial acetic acid at ratios of 27:20:52:1 respectively. The method was validated and found to be specific, precise, accurate and reproducible even when run at different times of the same day or on different times on different days. The limit of detection and quantification were determined to be 0.035 μg/ml and 0.0625 μg/ml respectively. It could be concluded that this method could be used to determine piroxicam concentration in the samples collected from in vitro study of permeability through the synthetic membrane and excised rat skin.Keywords: Piroxicam, HPLC, Quantification analysis, Modification

Stability Studies of Nano-Scaled Emulsions Containing Ibuprofen for Topical Delivery

Biphasic systems, like emulsions and nano-scaled emulsions, are naturally unstable. The extent and rate of the destabilization process differ from system to another. The stability of such systems upon storage is an important aspect to ensure their abilities to exert the expected effects and consequently render them pharmaceutically acceptable. In the present study, the stability of the nano-scaled emulsion containing newly synthesized palm oil esters (POEs) was assessed under different storage conditions and over specified durations. Three nano-scaled emulsion formulae were chosen for this investigation. They basically comprised ibuprofen as the active ingredient, triethanolamine aqueous solution pH 7.4 as the external phase, POEs as the oil phase, Tween 80 as an emulsifier, Carbopol® 940 as the rheology modifier and menthol or limonene as penetration promoters. The evaluation processes were carried out at several temperatures (4, 25 and 40 °C) with factors, such as droplets size, electrical conductivity, drug content, pH and flow properties were relatively held constant. The data collectively showed that all formulations were stable over an observation period of three months.Keywords: Ibuprofen, nano-scaled emulsion, palm oil esters, stabilit

Study of Pseudoternary Phase Diagram Behaviour and the Effect of Several Tweens and Spans on Palm Oil Esters Characteristics

Palm oil esters are high molecular weight esters oil that has been newly synthesized by University Putra Malaysia researchers. It has received a lot of attention for its pharmaceutical and chemical application. The aim of this study is to study the effects of the palm oil esters with different HLB surfactant mixture on the ternary diagrams behaviour and to confine the various systems resulted from these combinations. These systems include traditional emulsion, gel area, transpernat micro-emulsion area, O/W and W/O emulsions. In this study, pseudoternary phase diagrams of water, POEs and non-ionic surfactant mixture of several HLB values were constructed using water titration method. The resultant mixtures collected after each addition and mixing of water were analysed visually, along with conductivity, dilution in water and dye test (methylene blue) to classify them as O/W emulsion (transparent and opaque) or W/O (opaque) and liquid or gel. As a conclusion, palm oil esters were found to be suitable for the formulation of different types of emulsion. Additionally, different HLB value of non-ionic surfactant(s) exhibited different pseudoternary phase diagram characteristics.Keywords: palm oil esters, Tween, Span, Pseudoternary phase diagram, O/W emulsio