10 research outputs found
Communication: Effect of diperoxovandate on isolated rat heart
No full textDiperoxovanadate (DPV), a product of vanadate is gaining importance as a biologically active vanadium compound. The aim of the present study was to evaluate the chronotropic and inotropic activity of DPV using isolated rat heart and to determine the concentration at which it is toxic to the heart. The study was carried out using modified Langendorff\'s setup. DPV was injected at varying concentrations (from 10-9 to 10-4) either as bolus (0.1 ml) or the heart was perfused continuously with varying concentrations of DPV for 10 min. Low concentration of DPV did not produce any significant effect on chronotropy and on developed tension. However, as the dose of DPV was increased, tension developed and heart rate was enhanced to significant extent (P < 0.05) and both were found to be maximum at a dose of 10-7M. Further increase in DPV dose did not show either an increase in force or rate of contraction of heart but instead produced a relative decrease in both of these parameters when compared with the 10-7 M dose. When heart was perfused with a dose of 10-7 M DPV continuously for 10 min there was a significant increase in heart rate and developed tension (P < 0.01). It was also found that at a dose of 10-5M, DPV showed not only further increase in developed tension but also produced marked disturbances in the rhythm indicating cardiac toxicity. This was further confirmed by lactate dehydrogenase (LDH) activity determination.
Keywords: diperoxovanadate, reperfusion, isolated rat heart, hydrogen peroxide, lactate dehydrogenase
Ethiopian Pharmaceutical Journal, vol. 22 (2004): 47-5
Interaction of Propranolol with Garlic on Biochemical and Histological Changes in Rat
No full textAbstract The current study dealt with the interaction of garlic homogenate (GH) with propranolol (PRO) in rat, and to determine whether this effect is associated with biochemical and histological changes. Albino rats were treated with GH at three different doses of 125 mg/kg (GH-125), 250 mg/kg (GH-250) and 500 mg/kg (GH-500) orally for 30 days and PRO was incorporated in the interactive groups during the last seven days of GH treatment. Blood was withdrawn under ether anesthesia from the retroorbital route and serum was separated. Heart tissue homogenate (HTH) of the excised heart was also prepared. Both serum and HTH were used for biochemical estimation. Histopathological studies were carried out subsequently for confirmation of biochemical findings. GH-125 and GH-250 were found to significantly augment the endogenous antioxidant synthesis whereas, GH-500 was found to significantly diminish the synthesis of superoxide dismutase (SOD) and catalase. Toxicity of GH-500 cannot be reversed by the addition of PRO in the therapy. However, incorporation of PRO in GH-125 or GH-250 treatment showed significant synergistic effect in terms of increasing antioxidant synthesis. Mild and moderate doses of GH were also shown to keep the integrity of myocardium intact, whereas GH-500 damages the myocardium. The findings of the present study indicate that it is safe to administer garlic in low to moderate doses in cardiac patients receiving propranolol. However, high doses of GH are found to be toxic to myocardium and hence care should be taken for proper selection of doses
Pharmacodynamic and Pharmacokinetic Interactions of Propranolol with Garlic (<i>Allium sativum</i>) in Rats
No full textGarlic preparations and propranolol (PRO) are agents recognized as cardioprotective and potent antihypertensive agents when they are used individually. However, there is no report available to explain the role of combined therapy during simultaneous hypertension and myocardial damage in rats. We aimed to determine the pharmacokinetic and pharmacodynamic interaction of PRO with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of PRO was determined by HPLC method; while pharmacodynamic interaction was studied in animals with hypertension (10% fructose) and myocardial damage (isoproterenol, 175 mg kg−1, s.c. 2 days). PRO was given orally at 10 mg kg−1for 1 week, whereas, GH was administered at three different doses of 125, 250 and 500 mg kg−1, p.o. in their respective groups during fourth to sixth week of high fructose (HF) period, once daily. Systolic blood pressure (SBP), heart rate, cholesterol, triglycerides, glucose, creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase and catalase were measured and histopathological studies were carried out. The bioavailability and half life of PRO were significantly enhanced by 2- and 3-fold, respectively, in animals pretreated with garlic (250 mg kg−1). Administration of PRO and low to moderate doses of GH (125, 250 mg kg−1), either alone or together showed fall in fluid intake and body weight. The combined therapy of GH 250 mg kg−1and PRO was found to be most effective in reducing SBP, cholesterol, triglycerides and glucose. These observations suggest that careful addition of garlic in moderate doses in PRO regimen might result in beneficial effect during treatment of hypertensive animals with myocardial damage.</jats:p
The potential benefits of a garlic and hydrochlorothiazide combination as antihypertensive and cardioprotective in rats
No full textEffect of conventional antihypertensive drugs on hypolipidemic action of garlic in rats
No full text176-181The present study was undertaken to determine the possible alteration in hypolipidemic actions of garlic homogenate (GH) in presence of conventional antihypertensive drugs, propranolol (PRO), hydrochlorothiazide (HYD) and captopril (CAP). Albino rats fed with normal fat diet (NFD) or high fat diet (HFD) were treated with GH at three different doses (125, 250 and 500 mg/kg) orally for 30 days or in combination with PRO (10 mg/kg, po), HYD (10 mg/kg, po) and CAP (30 mg/kg, po) during last 7 days of GH treatment. After the treatment, total cholesterol (TC), LDL-cholesterol, triglyceride (TG) and HDL-cholesterol were measured in serum and antiatherogenic index was calculated. The result showed that moderate and high doses of GH possessed potential antiatherosclerotic property that was significantly attenuated by PRO and HYD. However, GH antihyperlipidemic activity was augmented by CAP. It was concluded that administration of PRO and HYD decrease the hypolipidemic effect of GH and administration of GH along with CAP augmented the hypolipidemic effect of GH in rats
Comparative evaluation of the potential anti-spasmodic activity of Piper longum, Piper nigrum, Terminalia bellerica, Terminalia chebula, and Zingiber officinale in experimental animals
No full textBackground: Spasm of muscle is one of the frequent complaints seen by most of the population worldwide. The present study evaluated the efficacy of some of the commonly used herbal extracts against known spasmogens, such as histamine and 5-hydroxytryptamine (5-HT). Material and methods: The study was conducted on isolated guinea pig ileum and rat uterus preparations using histamine and 5-HT, respectively. Five herbal extracts such as Piper longum (P.L), Piper nigrum (P.N), Terminalia bellerica (T.B), Terminalia chebula (T.C), and Zingiber officinale (Z.O) were tested. Herbal extracts at doses 50, 150, 500, 1500, and 5000 mcg/ml were pretreated to the isolated tissue preparation, and the contractile response of histamine and 5-HT was recorded. The efficacy and the inhibitory concentration (IC50) were calculated and statistically analyzed by one-way ANOVA. Results: The study indicated that all five herbal extracts produced a concentration-dependent suppression of histamine and 5-HT-induced responses. A significant (p < 0.05) non-competitive antagonism was observed against the known spasmogen induced smooth muscle contraction for P.L, P.N, T.B, and Z.O in both guinea pigs and rat uterus preparation. Moreover, P.L and P.N completely abolished (100%) the contractile response induced by histamine and 5-HT. Although, T.C produced a concentration-dependent reduction in known spasmogen-induced contraction but the response was found to be statistically non-significant (p greater than 0.05). Conclusion: The finding suggested that P.L. and P.N. have better activity in terms of reducing the spasmogenic contractions compared to other extracts. Additionally, T.B. and Z.O. can lessen the uterine and intestinal contractions brought on by spasmogens. Although P.L and P.N demonstrated better efficacy against the spasmogenic activity of histamine and 5-HT, more research, particularly on isolated phytochemicals of the extracts and involving different experimental models, is required before establishing the precise safety and efficacy against spasmogenic-induced disorders
New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels
No full textCardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds
Evaluation of solid-lipid nanoparticles formulation of methotrexate for anti-psoriatic activity
No full textBackground & Objectives: Methotrexate (MTX) is commonly used to manage psoriasis. The drug has erratic absorption characteristics and shows several complications. The present study uses different experimental models to evaluate the solid-lipid nanoparticles of MTX (SLN-MTX) for the anti-psoriatic effect. Methods: A prepared SLN-MTX formulation was used and its permeability studies were conducted on Wistar rat abdominal skin. The organ-level distribution of the drug in the formulation was tested in mice and the in-vitro anti-psoriatic activity was determined in CL-177; XB-2 keratinocytes cell lines. The efficacy of SLN-MTX formulation was compared with standard MTX and marketed MTX preparations. The results are analyzed statistically using the student’s t-test. Results: The data suggested that MTX from the formulation was slowly released and completely (80.36%) permeated through the skin. The flux and permeation data were found to be maximum for SLN-MTX compared to marketed and standard preparations. MTX in the formulation was found to be distributed more in the liver (67.5%) and kidney (2.34%). Further, SLN-MTX formulation showed dose-dependent inhibition on the growth of keratinocytes, and the cytotoxic concentration (CTC50) was found to be the least (518 mcg/ml). Interpretation & Conclusion: The findings suggested that MTX in solid-lipid nanoparticles could be a promising formulation for the management of psoriasis since the drug was slowly released, progressively inhibited the growth of keratinocytes, and distributed mostly in organs meant for elimination. More studies in this direction might establish the precise safety and efficacy of SLN-MTX formulation in psoriasis
Head-down tilt lithotomy position and well-leg compartment syndrome: An international survey of current practice
No full textAim: Well-leg compartment syndrome (WLCS) is a serious complication of prolonged surgery in the head-down tilt lithotomy (HDTL) position associated with increased postoperative morbidity and mortality. However, there is a lack of awareness and clinical guidance regarding prevention of WLCS. The aim of this study was to assess current HDTL-related practices and occurrence of WLCS among a global cohort of clinicians. Method: An international online survey of clinicians was conducted between July and December 2023. Data analysis involved descriptive statistics, machine learning techniques and qualitative content analysis. Results: A total of 595 clinicians from 71 countries and 14 specialities participated. Most (98%) reported routine use of HDTL, 27% of whom did not implement any preventive strategies. 'Leg rest' was the most reported preventive measure (41%), commonly initiated after 2 or 3 h of HDTL (79%), for 10-15 min (56%). Overall, 170 cases of WLCS were reported by 21% of respondents. The majority reported unilateral WLCS (81%) following a laparoscopic procedure (63%) performed in HDTL (64%). Only 28% of respondents discussed WLCS during consent for operations in HDTL. Machine learning identified 'duration of uninterrupted HDTL' as a positive predictor of the occurrence of WLCS (p < 0.001). Content analysis demonstrated that clinician perspectives and practices regarding WLCS are significantly influenced by personal experience, mostly due to a poor evidence base and lack of standardized institutional policies. Conclusion: Perioperative practices during procedures in HDTL vary substantially, and are primarily informed by clinician experience and preferences. There is a need for evidence-based consensus on best practices to enhance safety during procedures in HDTL
