Effect of gliclazide on cardiovascular risk factors involved in split-dose streptozotocin induced neonatal rat model: a chronic study

Background: The present study aimed at evaluating the effect of gliclazide on cardiovascular risk factors involved in type 2 diabetes mellitus using n-STZ rat model on a long term basis.Methods: The diabetic model was developed using a split dose of streptozotocin (50 mg/kg) intraperitoneally on 2nd and 3rd postnatal days. The diabetic rats were treated orally with gliclazide suspension at the dose of 10 mg/kg for 90 days. Cardiovascular risk factors such as systolic blood pressure, heart rate, lipid profile, creatine kinase and lactate dehydrogenase were evaluated at regular intervals along with fasting blood glucose (FBG) and oral glucose tolerance test.Results: Gliclazide did not alter FBG however improved the impaired glucose tolerance. The gliclazide treated rats did not develop hypertension and there was a significant difference (p<0.001) at the end of treatment when compared to the diabetic group which could be due to free radical scavenging property of gliclazide. Gliclazide treatment in n-STZ model was found to be effective in preventing hypertension, creatine kinase and lactate dehydrogenase activity. Also gliclazide was found to have beneficial effects on the impaired glucose tolerance, dyslipidaemia, adiposity index and total fat pad weight.Conclusions: To improve and prevent the cardiovascular risk factors involved in Type II diabetic patients, gliclazide could be clinically beneficial

Pharmacodynamic and Pharmacokinetic Interactions of Propranolol with Garlic (Allium sativum) in Rats

Garlic 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−1 for 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−1 and 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

Erectogenic and Aphrodisiac Effects of Butea frondosa

Butea frondosa Koenig ex Roxb. (BF) is traditionally used to manage male sexual disorders including erectile dysfunction (ED). Methanol extract of BF (bark) inhibited Rho-kinase 2 (ROCK-II) enzyme activity in vitro with an IC50 of 20.29±1.83 μg/mL. The relaxant effect of methanol extract of BF (MEBF) was studied on phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) isolated from young rats. The effect of MEBF treatment on sexual behaviour of both young (5 month) and aged (24 month) rats was also studied in addition to the influence on smooth muscle, collagen (collagen-I and -III) level in penis, and sperm characteristics of young and aged rats. MEBF relaxed CCSM up to 21.77±2.57% and increased sexual behavior of young and aged rats. This increase in sexual function could be attributed to ROCK-II inhibition and increase in ratio of smooth muscle to collagen level in rat penile tissue. Increased sperm production and decreased defective sperms in young and aged rats corroborate the usefulness of Butea frondosa in male infertility in addition to ED

Communication: Effect of diperoxovandate on isolated rat heart

Diperoxovanadate (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

Abstract 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

Effect of conventional antihypertensive drugs on hypolipidemic action of garlic in rats

176-181The 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

In vitro antioxidant activity of new thiophene ring-based compounds

Free radicals are implicated in causation of various histo-pathological disturbances like myocardial ischemia injury, cancer, neurodegenerative diseases, hepatic disorders etc. Newer chemical entities (SMRK-1 and SMRK-10) of thiophene class were synthesized and tested for the antioxidant property by super oxide scavenging effect and lipid peroxidation inhibition activity. The results indicated that SMRK-1 and SMRK-10 had shown more than 50% inhibition in the formation of blue formazan in superoxide scavenging activity and inhibition of lipid peroxidation to the extent of 65% by preventing pink chromogens. These observations suggest that the newer compounds (SMRK-1 and SMRK-10) at the tested doses possess an antioxidant effect. Keywords: thiophene derivatives, synthesis, antioxidant, superoxide scavenging, lipid peroxidation inhibition Ethiopian Pharmaceutical Journal Vol. 23 2005: 53-5

IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms

Objectives: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. Methods: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM- 133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. Results: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM- 133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/ kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, β-sitosterol, nonaeicosanol, β-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. Conclusion: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders

Comparative evaluation of the potential anti-spasmodic activity of Piper longum, Piper nigrum, Terminalia bellerica, Terminalia chebula, and Zingiber officinale in experimental animals

Background: 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