EFFECT OF OLMESARTAN AND LABETALOL ON OXIDATIVE STRESS AND ANTIOXIDANT STATUS IN SOUTH INDIAN HYPERTENSIVE PATIENTS

Objective: To evaluate the glutathione (GSH), lipid peroxidation, total antioxidant status levels (TAS), and liver function parameters such as serumaspartate transaminase (AST) and serum alanine transaminase (ALT) in South Indian hypertensive patients before and after olmesartan and labetaloltreatment.Methods: Total 69 subjects were selected for the study. Out of 69 subjects, 29 were healthy volunteers (HVs) and 40 subjects were hypertensivepatients. The patients both male and female within the age group of 20-65 years were selected. GSH, lipid peroxidation, TAS, AST, and ALT levelsin serum were estimated using reported methods. Individual methods were standardized, standard graphs were plotted, and the parameters weremeasured.Results: Significantly fewer levels of GSH and TAS and more levels of malondialdehyde were observed in untreated hypertensive patients as comparedwith HVs. After drug treatment, there was significant raise in the levels of GSH and TAS as compared with untreated patients. No significant changesin AST and ALT were observed in both olmesartan and labetalol group as compared with HVs.Conclusions: The antioxidant supplementation is warranted to protect from oxidative stress attack, and the drugs such as olmesartan and labetalolwere showing the significant protection against oxidative stress which can significantly reduce blood pressure and prevent possible complications inhypertensive patients.Keywords: Hypertension, Oxidative stress, Olmesartan, Labetalol, Antioxidant

Antioxidant, analgesic and anti-inflammatory activities of Leucas cephalotes (Roxb.ex Roth) Spreng

The whole plant of the methanolic extract from Leucas cephalotes was screened for invitro antioxidant (using the DPPH method), invivo analgesic (using hot plate test in mice) and anti-inflammatory (using rat paw edema test) activities. The methanolic extract of Leucas cephalotes (MELC) scavenged the DPPH radicals in a dose-dependent manner. The IC50 value to scavenge DPPH radicals was found to be 421.3µg/ml. A significant (pO extrato metanólico total de Leucas cephalotes foi submetido à triagem para as atividades antioxidante in vitro (utilizando o método DPPH), analgésica (utilizando teste da placa quente, em camundongos) e antiinflamatória (utilizando teste de edema da pata de rato), nas doses de 200 e 400 mg/kg. O extrato metanólico de Leucas cephalotes (MELC) inativou radicais difenil picril hidrazila (DPPH) de forma dose-dependente. O IC50 para essa atividade foi de 421,3 µg/mL. Observou-se atividade analgésica significativa (

CYTOTOXICITY EVALUATION OF CARBON NANOMATERIALS ON HUMAN CELL LINES USING MTT ASSAY

Objective: The aim of this study was to evaluate and compare the in vitro toxicity of three carbon nano particles on five different cell lines. Methods: Human alveolar epithelial (A549) cells, hepatocytes (Hep G2 cells), human embryonic kidney cells, HCT 116, and intestinal (P407 cells) cells were exposed to multi walled carbon nanotubes, carbon nano fibres and carbon nano rods. The adverse effects of carbon nano particles were analyzed after 48 h incubation with different cell lines using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. Results: Incubation of carbon nano particles with different cells produced a concentration-dependent inhibition of growth of the cells. The TC50 values (toxic concentration 50, i. e., concentration of particles inducing 50% cell mortality) of three nano particles was found to be in the range 28.29–46.35 µg/mL, and less than that of quartz (known toxic agent, 30.24-54.95 µg/mL). Conclusion: The results indicating the greater cytotoxic effect of carbon nano particles than quartz particles

Neuroprotective effect of derris indica seed extract attenuates amyloid beta plaques induce Alzheimer’s in mice model

The progression of Alzheimer's disease type dementia is carried on by the neurotoxic effects of amyloid beta (Aβ25-35) peptide accumulation. The hypothalamic-pituitary-adrenal(HPA) axis malfunctions and leads to higher levels of amyloid beta(Aβ) accumulation. In this work, we looked at how Derris indica extract affected mice brains that had undergone neurodegeneration caused by the Aβ. Derris indica seed extract(DISE) were administered to mice over the course of 21 days in two dosages (50 mg/kg and 100 mg/kg). On the 21st day, tests for spatial learning, habituation memory, short-and long-term memory, and stepdown inhibitory responses were carried out. Pro-and anti-inflammatory cytokines and antioxidants were assessed in brain tissues. A significant (p<0.01) improvement in habituation memory and the step-down inhibitory avoidance test was seen after receiving the DISE therapy, reduced escape delay considerably (p<0.01) enhanced cognitive progress in spatial learning. DISE may have an impact on neuroprotection as seen by the significant (p<0.01) decrease in proinflammatory and enhancement in IL-10 along with improved antioxidant indicators. According to investigations, the DISE enhance cognition by controlling neuro-inflammation and neuroimmune function, which are both controlled by the HPA axis, which mitigates stress. DISE might be promising therapeutics for neurodegeneration disorders such as AD

Fasting and Post Prandial Monitoring of Dipeptidyl Peptidase-Iv (Dpp-Iv) – A Biomarker To Assess Incretin Response In Type-2 Diabetes

Dipeptidyl peptidase-IV (DPP-IV) could serve as a potential biomarker in monitoring the disease progression and improvement on treatment. To investigate fasting & post prandial response of DPP-IV enzyme as indirect marker of incretin response failure after chronic treatment with metformin in type 2 diabetes. The study included twelve nondiabetic subjects, ten patients with glycosylated hemoglobin values (6-8 %) and fifteen patients with glycosylated hemoglobin greater than 8 % of type-2 diabetes patients of either sex with metformin treatment above 3 years were recruited. Fasting and post prandial DPP-IV levels were calculated. HbA1c was used to assess diabetes status. DPP-IV activity (fasting) in type 2 diabetic subjects with HbA1c> 8 % was significantly higher DPP-IV (44.67 ± 2.19 U/l) than in non diabetic subjects (24.39 ± 3.97 U/l). A significant correlation between DPP-IV (fasting / post prandial) and HbA1c (r = 0.821 & r = 0.732, P< 0.01) was observed in both diabetic (HbA1c 6-8, HbA1c < 8) patients. Hyperglycemia induces significant increase in serum DPP-IV activity in fasting condition and might contribute to the reduction in active glucagon like peptide-1(GLP-1) in type 2 diabetic subjects. In normal subjects during post prandial condition, there is sudden increase followed by decrease of GLP-1 due t

Population Pharmacokinetics of Pioglitazone in South Indian Type-II Diabetic Patients

Introduction: Population pharmacokinetics (PPK) is the study of this variability, its source and magnitude in populations. This information is usedto design dosage regimens that account for individual patient characteristics.Objective: The objective of this study was to perform a non-linear mixed-effects analysis of the pharmacokinetics of pioglitazone, indicated fortreating diabetes and to study the effect of covariates such as age, body surface area and creatinine clearance on the PPK of pioglitazone in SouthIndian diabetic patients.Materials and Methods: A simple, rapid, and sensitive isocratic high-performance liquid chromatography-ultra violet method for detection andquantification of pioglitazone in plasma had been developed. Intra- and inter-assay variations were <1 and <2% respectively. Recovery of pioglitazonewas 98-99%. A total of 137 blood samples for pioglitazone plasma concentration measurements following a single 15 mg dose of pioglitazone wereobtained from 43 subjects having age in between 18 and 75 years. The PPK model was built using NONMEM 7.2.0. The first-order (FO) and first-orderconditional estimation (FOCE) method was used to estimate base and covariate models for pioglitazone.Results: One-compartment model with FO absorption and elimination (ADVAN 2 TRANS 2) was best-fit to the plasma concentration-time dataof pioglitazone. A combined error model was best-described the pattern of residual and between subject variability. The final model estimates ofclearance (CL) and volume (V) estimated by FOCE method were 3.4 lt/hr and 43 L.Discussion: There were no past reports on PPK of pioglitazone. With covariate models, a significant decrease was observed in object function value,between and within subject variability when compared with base model. The model found to best describe the data following the FOCE method was:CL=CL=θ1*EXP ([η1] and V=θ2*EXP [η2]). These parameters are utilized for individualizing the loading and maintenance doses in diabetic patients.No factor was found as informative covariate of pioglitazone.Conclusion: In order to minimize the variability associated with drug exposure in Indian diabetic patients, the population parameter estimates weregiven without influence of covariates.Keywords: Covariate, Creatinine clearance, NONMEM, Pioglitazone, Residual variability

Anti-atherosclerotic effect of atorvastatin and clopidogrel alone and in combination in rats

698-703Atherosclerosis is a disease affecting arterial blood vessels due to the accumulation of macrophage white blood cells and low density lipoproteins. Effects of atorvastatin, a recently introduced lipid lowering statin was studied alone and in combination with clopidogrel in high fat diet fed atherosclerotic rats orally. Results showed significant reduction in total serum cholesterol and malondialdehyde levels and significant improvement in urine creatinine levels. Aortic cross sections of rats treated with clopidogrel alone showed reversal of atherosclerotic calcification. The same effect was observed with the combined treatment of clopidogrel and atorvastatin. Only atorvastatin treatment did not show any histological atheroprotective effect. Atorvastatin and clopidogrel alone and in combination have offered significant atheroprotective effect. No specific advantage was seen with combined treatment of atorvastatin and clopidogrel, moreover the advantages seen with independent drug administration also reduced with combined treatment

CYTOTOXICITY EVALUATION OF TITANIUM AND ZINC OXIDE NANOPARTICLES ON HUMAN CELL LINES

Objective: In vitro cytotoxicity evaluation of titanium dioxide, 20 nm (TNP 20) and zinc oxide, 20 nm (ZNP 20) nanoparticles (NP) were tested on different types of human skin (HaCat), lung (A549), liver (Hep G2) and colon (Caco-2) cell cultures in relevance to human risk assessmentMethods: The different concentrations of test TNP 20 and ZNP 20 1-300 µg/ml were exposed to determine the cell viability reduction on four human cell lines after 48 h post exposure using 3-(4, 5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The mitochondrial membrane activities of the viable cells were determined with intensity of formazon formation by interpreting ELISA absorbance values at 470 nm.Results: The percent of cytotoxicity was determined by comparing percentage of cell viability reduction of test with that of control. The ZNP 20 produced higher cytotoxicity at the doses 100 (p<0.05) and 300 (p<0.001) µg/ml significantly on tested four human skin (HaCaT), lung (A549), liver (Hep G2) and colon (Caco-2) cells compared to TNP 20. The tested NP induced lesser cytotoxicity at lower concentrations with 1 and 3µg/ml in all the tested four cell lines. The induced cytotoxicity was an indicator for increased intracellular reactive oxygen species which further cause's major cell damage and cell death.Conclusion: The tested NP were induced greater cytotoxicity in the colon, Liver, lung and skin cells at higher concentrations 100 and 300 µg/ml significantly. The cytotoxicity order of TNP 20 and ZNP 20 at the highest dose (300µg/ml) were concluded as Caco-2>Hep G2>A549>HaCaT for 48 h post exposed cells

PHARMACOKINETIC EVALUATION OF PLGA & PLA BASED LONG ACTING RELEASE (LAR) MICROSPHERE FORMULATIONS OF CETRORELIX IN RATS

Cetrorelix is one of the potent luteinizing hormone–releasing hormone (LH-RH) antagonist which is indicated in the treatment of preventing premature ovulation in IVF (in vitro fertilization) procedures. The objective of the study was to prepare different poly-lactic-coglycolic acid (PLGA) and Polylactic acid (PLA) based long acting release (LAR) microsphere formulations and to further evaluate the pharmacokinetics, invitro and invivo release of cetrorelix from these formulations. Microsphere 1 (MS1) and Microsphere 2 (MS2) formulations prepared with PLGA 50:50 and PLGA75:25 copolymers could sustain the release of drug for 14-28 days, whereas microsphere 3 (MS3) and microsphere 4 (MS4) formulations prepared with PLGA 85:15 copolymer and PLA could extend the release for 120days. On comparing the invitro and invivo release of the microsphere formulations it was observed that release under invivo conditions release was faster than under invitro conditions. It was observed that increase in the drug loading lead to higher rise in the initial cetrorelix plasma levels and further lead to shorter duration of release. On SC injection of MS1, MS2, MS3 & MS4 microspheres formulation to adult male Sprague Dawley rats at 0.25mg/kg lead to an initial rise in plasma cetrorelix levels which is of 23.812 ± 8.554 ng/mL, 150.701 ± 51.772 ng/mL, 57.581 ± 19.781 ng/mL and 164.466 ± 56.512 ng/mL at the median Tmax of 6hr for MS1-4 formulations respectively, where as a single subcutaneous (SC) administration of cetrorelix injection to rats at 0.25 mg/kg provided peak maximum concentration (Cmax) of 79.274 ± 17.734 ng/mL at 1.5 hr (Tmax). The exposure (AUC0-t) achieved by the microsphere formulations are of the order 628.059±127.706, 4814.86 ± 1729.582, 8324.062 ± 2859.633, 10414.69 ± 3577.844 and 15579.68 ± 5352.216 hr.ng/mL for Cetrotide® , MS1, MS2, MS3 and MS4 formulations respectively. When compared with Cetrotide® SC injection the exposures achieved by the microsphere formulations are of the order MS4 > MS3 > MS2 > MS1 formulations. Therefore based on the results of the study it can be concluded that PLGA and PLA microsphere formulations of cetrorelix can be of clinical relevance helping the patients to avoid multiple injections during their therapy. Keywords: Cetrorelix; Poly-lactic-coglycolic acid (PLGA); Polylactic acid (PLA); Subcutaneous; Pharmacokinetics; Long acting release (LAR