Mohammed Naseeruddin Inamdar

The potential for interaction of hydrochlorothiazide with garlic in rats.

The present study was undertaken to determine the pharmacokinetic and pharmacodynamic interaction of hydrochlorothiazide (HCTZ) with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of HCTZ was studied by HPLC method, while pharmacodynamic interaction was studied using diuretic activity, ECG and BP changes and isoproterenol (ISO) induced myocardial injury. HCTZ was given orally at 10mg/kg and GH was administered at three different doses of 125, 250 and 500 mg/kg, p.o. The CK-MB, LDH, SOD, catalase and histopathological studies were carried out. The administration of HCTZ in GH pretreated rats found to decrease the QRS duration, RR interval, QT segment, systolic blood pressure, heart rate, serum potassium level, serum LDH and serum CK-MB activities significantly. The diuretic effect of HCTZ was significantly increased in presence of GH; however, kaliuresis was significantly reduced in presence of GH 250 mg/kg. Histopathological studies of heart tissue reveal the protective effect of GH 250 mg/kg in presence or absence of HCTZ during ISO stress to myocardium. The pharmacokinetic studies show that GH increases the bioavailability and half-life, along with decrease in clearance and elimination rate of HCTZ when administered orally. It was concluded that careful addition of garlic in moderate doses might result in beneficial effect during treatment of hypertension in patients with myocardial stress as garlic causes substantial fall in excretion of potassium when compared to HCTZ alone treatment in rats. This could be important in reducing the dose of HCTZ to achieve enhanced therapeutic effect with minimal adverse effect.

Pharmacodynamic interaction of captopril with garlic in isoproterenol-induced myocardial damage in rat.

It is known that various preparations of garlic and angiotensin‐converting enzyme (ACE) inhibitor such as captopril (CAP) have beneficial effects on the left ventricular function and cardiovascular events after myocardial infarction (MI) when used individually. There is no reported interaction between garlic homogenate (GH) and CAP during and after acute MI. Thus the purpose of the current study was to evaluate the possible pharmacodynamic interaction of GH with CAP on isoproterenol (ISO)‐induced myocardial damage in rat. Female Wistar albino rats were treated with GH at three different doses of 125; 250 and 500 mg/kg orally for 30 days and CAP (30 mg/kg, p.o.) was incorporated in the interactive groups during the last seven days of GH treatment. Myocardial damage was induced by administration of ISO (150 mg/kg, s.c.) for two consecutive days. Biochemical parameters were studied in serum and heart tissue homogenate of all animals. The GH 250 mg/kg was found to dislodge the effect of ISO on superoxide dismutase and catalase and retained the activities of LDH and CK‐MB. Incorporation of CAP during GH treatment provided further protection to myocardium from injury. However, higher dose of GH alone or with CAP failed to prevent damaging effect of ISO. Histopathological determinations confirmed biochemical findings. Thus it is concluded that the combination needs to be used carefully when garlic is consumed at high doses. Copyright

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.

Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction.

Background: Diabetes induced sexual dysfunction is a leading cause of male sexual disorder and an early indicator of cardiovascular complication. Reactive oxygen species generated in body during diabetes is a main causative factor for erectile dysfunction, a sexual dysfunction. Adjuvant antioxidant therapy along with phosphodiesterases type 5 enzyme inhibitor (PDE5i) is more effective than PDE5i alone. Objective: The aim of the study was to investigate efficacy of ellagic acid a known antioxidant and sildenafil in diabetes induced erectile dysfunction. Materials and Methods: Type 1 diabetes was induced in male rats and rats were treated with ellagic acid (50 mg/kg, p.o.) and a combination of ellagic acid (50 mg/kg, p.o.) and sildenafil (5 mg/kg, p.o.), a PDE5i for 28 days. Sexual function was observed in diabetic rat and compared with those of treatment group and normal rats. Effect of ellagic acid was studied on advanced glycation end products (AGE) and isolated rat corpus cavernosum in vitro. Results: Sexual function of diabetic rats was found to be reduced and ellegic acid treatment could preserve sexual function of diabetic rats to some extent. Ellagic acid + sildenafil treatment was more efficient in management of diabetes induced sexual dysfunction. Ellagic acid inhibited (AGE) in vitro implying its role in reducing oxidative stress in diabetes. The polyphenol could not increase sexual function in normal rats and relax isolated rat corpus cavernosum smooth muscle significantly. Conclusion: The study proves usefulness of adjuvant antioxidant therapy in the management of erectile dysfunction in diabetes.

Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats.

Introduction Diabetes-induced sexual dysfunction is associated with an increase in oxidative stress. Scavengers of reactive oxygen species (ROS) have been shown to reduce oxidative stress and aid in the management of sexual dysfunction in diabetes. Aim The aim of the study was to test the hypothesis that antioxidant, which scavenge ROS and reduce formation of advanced glycation end products (AGEs), can potentiate efficacy of phosphodiesterase type 5 inhibitors in diabetes-induced sexual dysfunction that is associated with oxidative stress. Materials and Methods Effect of phloroglucinol and sildenafil on serum glucose level, sexual function, penile smooth muscle : collagen ratio, and phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) was studied. The ability of phloroglucinol to reduce the formation of AGEs and its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) was also evaluated. Main Outcome Measures Antioxidant potential of phloroglucinol was studied in addition to its effect on diabetes-induced sexual dysfunction in presence and absence of sildenafil. Results Phloroglucinol (50 mg/kg, p.o.) significantly decreased serum glucose level and increased sexual function in streptozotocin-induced diabetic rats when compared with diabetic control rats. Sildenafil (5 mg/kg, p.o.) had no effect on glycemia but significantly increased sexual function of diabetic rats. Coadministration of phloroglucinol increased the efficacy of sildenafil by improving sexual function. Treatment of diabetic rats with phloroglucinol + sildenafil maintained smooth muscle : collagen levels similar to that of normal rat penile tissue. Phloroglucinol decreased formation of AGEs and significantly scavenged DPPH radical activity in vitro. Sildenafil relaxed isolated CCSM of normal rat and diabetic rat significantly, but phloroglucinol did not show any significant effect. Phloroglucinol also inhibited human CYP3A4 enzyme activity in vitro. Conclusion Phloroglucinol coadministration increases efficacy of sildenafil in diabetes-induced sexual dysfunction. However, further studies are required to ascertain the benefits of phloroglucinol owing to its undesirable CYP3A4 inhibition activity.

Effect of Cinnamomum cassia Methanol Extract and Sildenafil on Arginase and Sexual Function of Young Male Wistar Rats

INTRODUCTION Herbs have been used as an aphrodisiac since ages. Cinnamomum cassia is an important ingredient of many Ayurvedic formulations to treat male sexual disorder including erectile dysfunction (ED). AIM The objective of the present study was to evaluate erectogenic and aphrodisiac activity of methanol extract of C. cassia bark in young male rats. METHODS Methanol extract of C. cassia was screened in vitro for arginase inhibition potential and IC50 was determined. Effect of the extract was observed in vitro on phenylephrine pre-contracted isolated rat corpus cavernosum smooth muscle (CCSM) at 0.1, 1, 10, and 100 μg/mL. Young male Wistar rats were dosed with extract at 100 mg/kg body weight for 28 days and its effects on sexual behavior and penile smooth muscle : collagen level were observed. MAIN OUTCOME MEASURE Effect of C. cassia was studied on arginase activity in vitro and sexual behavior of young male rats. RESULTS C. cassia inhibited arginase activity in vitro with an IC50 of 61.72 ± 2.20 μg/mL. The extract relaxed phenylephrine pre-contracted isolated rat CCSM up to 43% and significantly increased (P < 0.05) sexual function of young male rats. Treatment with the extract also increased smooth muscle level and decreased collagen level in rat penile tissue. CONCLUSION The study proves usefulness of methanol extract of C. cassia bark for increasing sexual function.

Modulation of haemodynamics, endogeneous antioxidant enzymes, and pathophysiological changes by selective inhibition of angiotensin II type 1 receptors in pressure-overload rats : cardiovascular topics

Background Constriction of the thoracic or abdominal aorta provides an experimental model of pressure-overload cardiac hypertrophy. Blockade of AT1 receptors is beneficial in preventing target-organ damage in hypertension. Objective To examine the effect of angiotensin II receptor antagonists on blood pressure, endogenous antioxidant enzyme and histopathological changes in pressure-overload rats. Methods Pressure overload was produced by abdominal aortic banding (AAB) using a blunt 22-guage needle in male rats as a model of cardiac hypertrophy. After surgery, the AAB-induced hypertension (AABIH) rats were treated with losartan 40 mg/kg/day, candesartan 10 mg/kg/day, irbesartan 10 mg/kg/day per os for 16 weeks. At 16 weeks of surgery, the rats were observed for general characteristics and mortality, and we determined non-invasive blood pressure (NIBP), endogenous antioxidant enzyme catalase and superoxide dismutase (SOD) activities, and histology of the target organs. Results In the AABIH group, significant increase in systolic blood pressure was observed from weeks 3 to 16 compared with the control group, along with reduced serum catalase and SOD activities. The treated groups showed significant reduction in systolic BP and increase in serum SOD and catalase activities. The histological changes induced in the target organs, namely heart, liver, kidneys and thoracic aorta in the AABIH rats were attenuated in the treated rats. Conclusion Blockade of the AT1 receptor caused an improvement in the myocardial antioxidant reserve and decreased oxidative stress in the hypertensive rats, which was evidenced by the protection observed in the treatment groups.

Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of Soluble Epoxide Hydrolase Enzyme

Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile erection; therefore, sEH could be useful for management of erectile dysfunction. Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for their sEH inhibition potential. Fifteen extracts showed >50% inhibition when screened at 50 µg/mL in sEH inhibition assay. Methanolic extract of Moringa oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 ± 0.1 µg/mL and was selected for in vitro studies on isolated rat corpus cavernosum smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats. Rats were divided into five groups, each containing six animals and treated orally with either water, vehicle (1% Tween‐20), MEMO (45 and 90 mg/kg/day for 21 days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of female rats were used, and the effect of MEMO and sildenafil was compared with that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth muscle at 0.1–100 µg/mL in vitro and significantly increased (p < 0.05) sexual activity, intracavernous pressure/mean arterial pressure in normal and diabetic rats. The increase in erectile function of rats by MEMO could be because of its sEH inhibitory activity. Copyright

The critical steps for successful research: The research proposal and scientific writing

An interactive workshop on ‘The Critical Steps for Successful Research: The Research Proposal and Scientific Writing’ was conducted in conjunction with the 64th Annual Conference of the Indian Pharmaceutical Congress-2012 at Chennai, India. In essence, research is performed to enlighten our understanding of a contemporary issue relevant to the needs of society. To accomplish this, a researcher begins search for a novel topic based on purpose, creativity, critical thinking, and logic. This leads to the fundamental pieces of the research endeavor: Question, objective, hypothesis, experimental tools to test the hypothesis, methodology, and data analysis. When correctly performed, research should produce new knowledge. The four cornerstones of good research are the well-formulated protocol or proposal that is well executed, analyzed, discussed and concluded. This recent workshop educated researchers in the critical steps involved in the development of a scientific idea to its successful execution and eventual publication.