Pathophysiological Significance And The Role Of Exogenous Hydrogen Sulfide (H2S) In A Combined State Of Hypertension And Diabetes And Its Effect On Renal Excretory And Haemodynamic Functions

Hypertension and diabetes is a common co-morbidity that often coexists. Both diseases serve to induce and exacerbate each other. Hypertension and diabetes predispose the development of cardiovascular disease (CVD) and renal disease as their major complications. Coexistence of hypertension and diabetes results in rapid development of nephropathy. Endogenous H2S is recognized as a novel gaseous transmitter. Vascular tissues are capable of generating the measurable amounts of H2S with a concentration of ~46μM in the rat serum. H2S is involved in the regulation of blood pressure and also implicated in controlling the renal glomerular (vascular) and tubular functions. Present study was undertaken to test the hypothesis that exogenous H2S lowers the blood pressure and decreases the progression of nephropathy in hypertensive diabetic rats. SHR and DOCA-salt hypertension rat models were used in this study. DOCA-salt hypertension was produced from WKY rats. Diabetes was induced with a single injection of streptozotocin (STZ) at a dose of 40 mg/kg in freshly prepared ice cold sodium citrate buffer (0.1 mol/L, pH 4.5), intraperitoneally. One set of diabetic groups received NaHS, a H2S donor, at a dose of 56μmol/kg intraperitoneally in saline at the same time daily for 5 weeks. Blood pressure was measured in conscious rats and at the end of the treatment period in surgically prepared anesthetized rats. In addition, pulse wave velocity (PWV) and renal cortical blood perfusion were also observed. Metabolic data collection for renal function study was performed on days 0, 21 and 33 of a 35-day study. Plasma and urinary H2S levels, creatinine concentrations and electrolytes were measured on three different occasions throughout the 35-day period. Plasma and urinary H2S and creatinine concentrations were measured spectrophotometrically. Data, mean±SEM were analyzed using ANOVA and statistical significance was set at p < 0.05. Diabetic hypertensive groups of rats had higher blood pressure, low plasma and urinary H2S levels and renal dysfunction as evidenced by increased plasma creatinine, creatinine clearance and decreased urinary sodium to potassium ratio and renal cortical blood perfusion. In addition diabetic hypertensive rats had higher pulse wave velocity. Moreover diabetic rats exhibited increased creatinine clearance, plasma sodium, absolute sodium excretion and fractional sodium excretion. NaHS, a donor of exogenous H2S reduced the blood pressure and pulse wave velocity, increased the H2S levels in hypertensive diabetic rats and reversed the STZ-induced renal dysfunction. In addition, exogenously administered H2S decreased the plasma sodium and increased the creatinine clearance and absolute sodium excretion in treated rats. The findings of the present study suggest that exogenously administered hydrogen sulfide lowers the blood pressure and significantly reverses the STZ-induced increase in plasma creatinine, decrease in urinary sodium potassium ratio and reduced renal cortical blood perfusion, thereby conferring the protection against the progression of STZ-induced nephropathy in hypertensive rats

ADIPONECTIN VERSUS THIAZOLIDINEDIONES AND ANGIOTENSIN RECEPTOR BLOCKERS

Adipose tissue has gained great attention during the last decade. It represents not only a depot for energy stores, but also releases adipocytokines regulating energy disposal and can therefore be considered from therapeutic point of view. Hypoadiponectemia is an independent threat for development of metabolic syndrome. When subjects treated with antidiabetic (Thiazolidinediones) and antihypertensive (angiotensin receptor blocker) agents , the plasma concentration of adiponectin, the only component of adipocytokines, directly proportional to plasma values of these drugs. The prevalance of hypertension and T2DM is mounting with unprecedented degree in both developing and advanced countries, therefore, there is a dire need to find safer and economical therapeutic regimes for the treatment of these ailments, and intensive research is also underway for this purpose. PPARγ serves as a common link in the actions of ADN, TZDs and ARBs when exerting their effects, and it is responsible for stimulation of adiponectin receptors, thus ultimately enhancing the levels of adiponectin in plasma. This review aims to elucidate the role, link and use of ARBs, ADN and TZDs as a safer and convenient approach for the treatment of these co-morbidities as a unanimous or single remedy from comparative point of view

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

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08-206.4 ± 2.26 nm, zeta potential was -17.8 ± 1.26 to -24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site

Frequency and predictors of anxiety and depression among pregnant women attending tertiary healthcare institutes of Quetta City, Pakistan

Abstract Background Anxiety and depression (A&D) are commonly reported among pregnant women from all over the world; however, there is a paucity of workable data from the developing countries including Pakistan. The current study, therefore, aims to find out the frequency and predictors of A&D among pregnant women attending a tertiary healthcare institutes in the city of Quetta, in the Balochistan province, Pakistan. Methods A questionnaire based, cross-sectional survey was conducted. The pre-validated Hospital Anxiety and Depression Scale (HADS) were used to assess the frequency of A&D among study respondents. Anxiety and depression scores were calculated via standard scoring procedures while logistic regression was used to identify the predictors of A&D. SPSS v. 20 was used for data analysis and p < 0.05 was taken as significant. Results Seven hundred and fifty pregnant women responded to the survey. The majority of the respondents belonged to age group of 26–35 year (424, 56.4%) and had no formal education (283, 37.6%). Furthermore, 612 (81.4%) of the respondents were unemployed and had urban residencies (651, 86.6%). The mean anxiety score was 10.08 ± 2.52; the mean depression score was 9.51 ± 2.55 and the total HADS score was 19.23 ± 3.91 indicating moderate A&D among the current cohort. Logistic regression analysis reported significant goodness of fit (Chi square = 17.63, p = 0.030, DF = 3), indicating that the model was advisable. Among all variables, age had a significant association when compared with HADS scores [adjusted OR (odds ratios) = 1.23, 95% CI = 1.13–1.62, p < 0.001]. Conclusion Moderate A&D was reported among the study respondents. Furthermore, age was highlighted as a predictor of A&D. The evidence from this study provides a motion of support programs for anxious and depressed pregnant women. The benefits of implementing good mental health in antenatal care have long-lasting benefits for both mother and infant. Therefore, there is a need to incorporate A&D screening in the existing antenatal programs

A multidirectional phytochemical profiling, antimicrobial, antioxidant and toxicity studies of Neurada procumbens L.: A desert medicinal plant

Objectives: Neurada procumbens L. (Neuradaceae) is a Cholistani desert plant traditionally employed in fever, inflammations, diabetes and hepatitis. The purpose of this study was to determine the chemical composition, anti-bacterial, antibiofilm and antioxidant activities of various extracts of this important medicinal plant; separately for its aerial and floral parts. Methods: The phytochemical screening (by HPLC analysis), antioxidant (by DPPH assay), antibacterial (by disc diffusion test and MIC) and anti-biofilm potential against seven bacterial strains (E. coli, K. pneumoniae, S. aureus, S. aureus MDR, P. aeruginosa, P. aeruginosa MDR and P. vulgaris) were determined by aqueous, methanol, n-butanol, ethyl acetate, n-hexane and dichloromethane extracts of floral and aerial parts of N. procumbens. Results: The floral MetOH and DCM extracts were found to contain higher polyphenolic contents including 2,3-di methoxy benzoic acid (38.21 µg/mg), chlorogenic acid (26.59  µg/mg) and catechin (14.24 µg/mg) and exhibited a comparatively higher antioxidant (IC50 13.5 mm zone of inhibition and MICs 62.5–125 µg/ml) against P. aeruginosa MDR and S. aureus in anti-bacterial activity. In an anti-biofilm assay, MetOH and DCM floral extracts showed a promising potential (>85 % biofilm inhibition) with IC50 < 150 μg/ml against P. aeruginosa MDR and S. aureus MDR better than moxifloxacin and was further confirmed by light and scanning electron microscopy. Moreover, the floral-MetOH extract of N. procumbens has been found to be safe up to 2 g/kg BW with its lethal dose (LD50) as 3872.98 mg/kg BW in rats. Conclusion: Hence, due to presence of essential medicinal compounds with low toxicity effects, the plant is recommended to be safely employed in various pharmaceutical preparations

Antioxidant and anti-inflammatory potentials of aerial and floral parts of Neurada procumbens extracts: In vitro and in vivo studies

Neurada procumbens (Neuradaceae) is an importent plant of the Cholistan desert and is traditionally been used for the treatment and control of diabetes, fever, inflammations and jaundice. The aim of the current project is to investigate the bioactive compounds, free radical scavenging capacity and the anti-inflammatory potential of Neurada procumbens separately for its aerial and floral parts in six different extracts. The phytochemical profile (total bioactive contents, HPLC polyphenolic quantification), anti-oxidant (DPPH and FRAP assays), anti-inflammatory (HRBC stabilization) activities of the Aqu, MetOH, n-But, EtAc, n-Hex, and DCM extracts from the aerial and floral parts of Neurada procumbens were quantified. Based on the current results, the aerial and floral parts of N. procumbens extracts have found to contain a significant amount of active metabolites including polyphenolic compounds such as 2,3 di MeO benzoic acid, p-coumaric acid, chlorogenic acid, quercetin dihydrate and t-ferrulic acid. The total phenolic and total flavonoid contents of the plant were found to range from 28.13 to 78.9 GAE mg/g of plant and 17.23 to 68.23 RE mg/g of plant, respectively. DCM and n-But extracts of floral part exhibited comparatively higher antioxidant potential in DPPH (IC50 < 100 μg/ml) and FRAP (IC50 < 55 μg/ml) assays compared to aerial part. The dichloromethane floral extract demonstrated impressive anti-inflammatory activity in the hemolytic red blood cell lysis assay, with 83 % protection of HRBC lysis at an IC50 of 469.6 µg/ml (p < 0.01). In vivo, a 300 mg/kg body weight of DCM floral extract reduced carrageenan-induced paw oedema by 8.51 ± 0.35 mm to 7.65 ± 0.38 mm, a highly significant difference (p < 0.001).The toxicity studies revealed that the floral-DCM dose extract was found to be safe up to 2000 mg/kg BW, while its lethal dose (LD50) was found to be 4472.13 mg/kg BW in rats. Due to quite low toxicity effects, the floral part of the plant could be recommended as a safe pharmacological agent for various therapeutic applications