Ipseeta Ray Mohanty

Histopathological and ultra structural effects of nanoparticles on rat testis following 90 days (Chronic study) of repeated oral administration

BackgroundNanoparticles (Ag NPs) have recently received much attention for their possible applications in biotechnology and biomedical. However, little is known about the toxicity in reproductive organs of animal model following exposure to nanoparticles.ObjectiveThis study therefore, tried to examine the effects of nanoparticles with a diameter range of 5-20 nm on the histology of the testis of wistar rats and correlate it with Transmission Electron Microscopy results.Materials and methodsSixteen wistar rats were randomly divided into two groups of 8 rats each. Each group received the following via gavage technique for 90 days: Control Group (Group-1)-tap water; Experimental group (Group 2) - nanoparticles (20ug/kg/day). After ninety days (chronic study), rats were sacrificed and testis tissues was processed for histology and transmission electron microscopic study.ResultsThere was significant difference between the observations of group-1 and group 2. The changes observed in the testis were disarray of the spermatogenic cells and disorientation of the testis. These changes were observed to have been disappearing from normal histological features. Detailed structural damages were observed with TEM analysis, such as depletion of germ cells, germinal cells necrosis, especially in spermatogonia and Leydig cells had an abnormal fibroblast-like appearance, abnormal space between neighboring sertoli cells, mitochondria, lost cristae and vacuolated (none energized) with those animals exposed to nanoparticles.ConclusionIt seems that nanoparticles have acute and significant effects on spermatogenesis and number of spermatogenic cells. More experimental investigations are necessary to elucidate better conclusion regarding the safety of nanoparticles on male reproduction system.

Bacopa monniera protects rat heart against ischaemia–reperfusion injury: role of key apoptotic regulatory proteins and enzymes

Objectives  Rat isolated hearts were perfused in a Langendorff model to study the cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian system of medicine, on cardiomyocyte apoptosis and antioxidant status following ischaemia–reperfusion (I‐R) injury.

Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

Myocardial Salvaging Effects of Berberine in Experimental Diabetes Co-Existing with Myocardial Infarction

INTRODUCTION Berberine, an isoquinoline alkaloid isolated from the Berberis aristata, has been shown to display a wide array of pharmacological activities (hypoglycaemic and hypolipidemic). AIM The present study was designed to investigate whether these pharmacological properties translate into the cardioprotective effects of Berberine in the setting of diabetes mellitus. MATERIALS AND METHODS Necessary approval from the Institutional Animal Ethics Committee was taken for the study. Experimental diabetes was produced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was induced by administering Isoproterenol (ISP): 85mg/kg, sc to rats on 35(th) & 36(th) day. After the confirmation of diabetes on 7(th) day (>200mg/dl), Berberine (100 mg/kg) was administered orally to experimental rats from day 8 and continued for 30 days thereafter. Various anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB), metabolic (lipid profile), safety {liver function (SGPT, kidney function (Creatinine)} and histopathological indices of injury were evaluated in Healthy Control, Diabetic Control and Berberine treated groups. RESULTS Administration of STZ-ISP resulted in a significant decrease in body weight (p<0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, SGPT, creatinine levels (p<0.001) in the diabetic control group rats as compared to healthy control. Berberine treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p<0.001) compared to diabetic control group. In addition, Berberine favourably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL). Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Berberine in setting of diabetes. In addition, Berberine was found to be safe to the liver and kidney. CONCLUSION Berberine treatment produced myocardial salvaging effects in the setting of diabetes challenged with ISP induced myocardial necrosis. Cardioprotection may be attributed to anti-diabetic and hypolipidemic activities.

Drug Utilization studies in Glaucoma patients at MGM medical College and Hospital

The present study evaluated the pattern of drug usage for glaucoma. A Proforma was designed specifically for the study factoring patients’ demographical profile, prescription regimen. A total of 100 prescriptions of patients suffering from glaucoma were analyzed. Maximum cases (36%) belonged of age group 40 to 50 years with a gender ratio (Male/female) of 2.3. All the patients were diagnosed as suffering from primary open angle glaucoma out of which 82% had bilateral glaucoma. The average number of drugs per prescription was 1.23. The total no. of drug prescribed was 123 and 18% of prescriptions showed polypharmacy practice. Most commonly prescribed drug was Timolol (41%), followed by Brimonidine 16.26%. Bimatoprost (12.19%), Dorzolamide (11.38%), Latanaprost (5.69%). Fixed dose combination (Latanoprost+Timolol) was encountered in 14% of the glaucoma patient’s prescription, who had high intraocular pressure. Prescription of drugs by brand names instead of the recommended generic names is a matter of concern. Drug Utilization studies in Glaucoma patients at MGM medical College and Hospital

Tribulus teresstris modulates heat shock protein and key anti-apoptotic proteins in the Langendorff model of myocardial ischemia and reperfusion injury

The cardioprotective effects of Tribulus teresstris (Tt), a medicinal herb, used in Indian system of medicine was evaluated in the Langendorff model of myocardial ischemia and reperfusion (I-R) injury. Tt (1, 2.5, 5, 10 mg/kg) was orally fed to healthy experimental rats once a day for 21 days followed by global ischemia and reperfusion injury. Biochemical parameters: lipid peroxidation product thiobarbituric acid reactive substances (TBARS), endogenous antioxidant: glutathione, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GSHPx)) and myocardial enzyme creatine phosphokinase (CPK) were evaluated. To correlate the biochemical derangement and altered cardiac performance during I-R, changes in the hemodynamic variables heart rate (HR) and coronary perfusion pressure (CPP) was measured. Myocardial apoptotic was quantified using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax, enzyme: Caspase 3 and heat shock protein (HSP) in cardiac myocytes was detected by immunohistochemistry. As compared with sham group, the CPP, TBARS levels, myocardial apoptosis, expression of Caspase 3, Bax, heat shock protein (HSP 72) proteins were increased significantly in I-R control group. Tt pre-treatment significantly restored the antioxidant network of the myocardium, reduced myocardial apoptosis, Bax, HSP 72 protein expression. These beneficial effects also translated into favourable hemodynamic effects. Histopathological studies and myocardial CPK content further confirmed the cardioprotective effects of Tt (2.5 mg/kg) in the experimental model of I-R injury.

Dipeptidyl peptidase IV Inhibitory activity of Terminalia arjuna attributes to its cardioprotective effects in experimental diabetes: In silico, in vitro and in vivo analyses

BACKGROUND The marketed synthetic (Dipeptidyl peptidase-IV) DPP-IV Inhibitors are expensive antidiabetic drugs and have been reported to cause unacceptable adverse effects such as pancreatitis, angioedema, thyroid and pancreatic cancers. In this scenario research to develop novel DPP-IV Inhibitors from alternative sources is the need of the hour. HYPOTHESIS/PURPOSE Terminalia arjuna, a medicinal herb with antidiabetic and cardioprotective activities may represent a natural DPP-IV Inhibitor, the DPP-IV Inhibitory activity of which may translate into demonstrable therapeutic benefits in setting of diabetes with cardiovascular co-morbidities. STUDY DESIGN The study type used for the present study was an experimental (In vitro, In vivo and In silico) design. METHOD The DPP-IV Inhibitory, antidiabetic and cardioprotective effects of Terminalia arjuna was evaluated in the experimental model of myocardial infarction co-existing with diabetes. To determine the active principle of Terminalia arjuna responsible for DPP-IV Inhibitory activity, the crystal structure of DPP-IV was considered as receptor which was docked against Arjunetin, Arjungenin, Arjunic acid, Arjunone, Ellagic acid, Gallic acid, Sitagliptin and Vildagliptin. The binding sites as well as affinity of various active ingredients of Terminalia arjuna for DPP- IV enzyme was elucidated using in silico studies and compared to Vildagliptin. RESULTS Terminalia arjuna demonstrated significant DPP-IV Inhibitory, antidiabetic (significant reduction in HbA1C) and cardioprotective effects (restoration of myocardial CPK-MB) in the experimental model of myocardial infarction co-existing with diabetes. The cardioprotective efficacy correlated to its DPP-IV Inhibitory activity. The active ingredients of Terminalia arjuna (Arjunetin, Arjungenin, Arjunic Acid Arjunone, Ellagic acid and Gallic acid) demonstrated significant inhibition of DPP-IV enzyme. Arjunic acid and Arjunone prefers the active site pocket of DPP-IV enzyme. Compounds like Arjunetin and Vildagliptin prefers to bind near the interface region of the DPP-IV as their biological active forms are homodimer. Sitagliptin binds near the α/β hydrolase domain. CONCLUSION The DPP-IV Inhibitory activity of Terminalia arjuna was found to be comparable to Vildagliptin. The DPP-IV Inhibitory activity translated into significant cardioprotective effects in the setting of diabetes. The active ingredient of Terminalia arjuna; Arjunetin, Arjungenin, Ellagic acid and Arjunic acid showed superior DPP-IV Inhibitory activity as compared to synthetic DPP-IV inhibitors (Sitagliptin and Vildagliptin) based on results of docking studies.

Natural dipeptidyl peptidase-IV inhibitor mangiferin mitigates diabetes- and metabolic syndrome-induced changes in experimental rats

Background Mangiferin (MNG) is known to possess antidiabetic and antioxidant activity. However, there is no experimental evidence presently available in the literature with regard to its ameliorating effects on diabetes mellitus coexisting with metabolic syndrome. Objective The present study was designed to evaluate the protective effects of MNG on various components of metabolic syndrome with diabetes as an essential component. Material and methods Adult Wistar rats were fed high-fat diets for 10 weeks and challenged with streptozotocin (40 mg/kg) at week three (high-fat diabetic control group). After the confirmation of metabolic syndrome in the setting of diabetes, MNG 40 mg/kg was orally fed to these rats from the fourth to tenth week. Results The treatment with MNG showed beneficial effects on various components of metabolic syndrome, such as reduced dyslipidemia (decreased triglyceride, total cholesterol, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol) and diabetes mellitus (reduced blood glucose and glycosylated hemoglobin). In addition, an increase in serum insulin, C-peptide, and homeostasis model assessment-β and a reduction in homeostasis model assessment of insulin resistance-IR were observed in MNG-treated group compared with high-fat diabetic control group. MNG was also found to be cardioprotective (reduction in creatine phosphokinase-MB levels, atherogenic index, high-sensitivity C-reactive protein). Reduction in serum dipeptidyl peptidase–IV levels in the MNG-treated group correlated with improvement in insulin resistance and enhanced β-cell function. Conclusion The present study has demonstrated antidiabetic, hypolipidemic, and cardioprotective effects of MNG in the setting of diabetes with metabolic syndrome. Thus, MNG has the potential to be developed as a natural alternative to synthetic dipeptidyl peptidase-IV inhibitors beneficial in this comorbid condition.