Open Access Original Research Article

Alterations in Biochemical Indices and Antioxidant Status in Rats Following Treatment with Gatifloxacin

Ebenezer Tunde Olayinka, Ayokanmi Ore, Oluwatobi Adewumi Adeyemo

Journal of Pharmaceutical Research International, Page 293-305
DOI: 10.9734/BJPR/2015/16210

Aim: Gatifloxacin (GTX) - an 8-methoxy fluoroquinolone antibacterial agent has been considered very effective in the treatment of respiratory and urinary tract infections. This study investigates the toxic potentials of GTX in Wistar rats.
Methodology: Twenty male rats (180-220 g) were randomised into four groups: I-Control, II-4 mg/kg body weight (b.w.) GTX, III-8 mg/kg b.w GTX, and IV-16 mg/kg b.w GTX.
Results: After seven days of GTX administration, the levels of plasma creatinine, urea and bilirubin were increased significantly (P<0.05) in GTX-treated rats compared to control. ALP, ALT, AST and GGT activities were also elevated significantly in the plasma of the treated animals relative to control. Similarly, hepatic malondialdehyde level increased significantly in the GTX-treated groups relative to control. Hepatic levels of ascorbic acid, reduced glutathione as well as activities of hepatic GST, catalase, and SOD were reduced significantly in a dose dependent manner in the GTX-treated animals compared to control. Besides, histopathological studies revealed very mild, moderate and severe hepatic portal congestion and cellular infiltration by mononuclear cells by the three doses of GTX.
Conclusion: Overall, three different doses of Gatifloxacin (half-therapeutic, therapeutic and double-therapeutic) induced renal and hepatic damages, as well as oxidative stress in rats.

Open Access Original Research Article

Strong Protein Glycation Inhibitory Potential of Clove and Coriander

H. K. I. Perera, D. C. R. Wijetunge

Journal of Pharmaceutical Research International, Page 306-312
DOI: 10.9734/BJPR/2015/16190

Aims: Protein glycation mediates almost all chronic diabetic complications associated with hyperglycaemia. In view of searching for safe antiglycating agents from nature, the protein glycation inhibitory potential of three spices was determined using a novel, electrophoresis based method.
Study Design: Dry plant parts, standard inhibitor, extraction, in vitro glycation model, gel electrophoresis.
Place and Duration of Study: Department of Biochemistry, Faculty of medicine, University of Peradeniya, Sri Lanka, between June 2012 and December 2013.
Methodology: Methanolic extracts of dried Coriandrum sativum (Coriander) seeds, Cinnamomum zeylanicum (Cinnamon) bark and Syzygium aromaticum (Clove) flower buds were used. Bovine serum albumin (BSA) was incubated with fructose in phosphate buffer (pH 7.4) at 37ºC for 30 days in the presence or absence of the extracts. Corresponding blanks, controls and the standard glycation inhibitor aminoguanidine were included. Aliquots were collected at intervals and analyzed using polyacrylamide gel electrophoresis under non denaturing conditions (PAGE). Antiglycating effects of the extracts were assessed based on the decrease in migration of BSA.
Results: Previously, we have demonstrated using PAGE, that the increase in BSA migration, in comparison to the blank is proportionate to the degree of glycation. In presence of C. sativum and S. aromaticum,migration of BSA was reduced with extract concentrations as low as 10 µg/ ml, compared to its migration in absence of the extract (positive control), indicating strong glycation inhibitory effects of the extracts. C. zeylanicum showed antiglycating effects at 5 mg/ ml but not at 0.5 mg/ ml.
Conclusion: This study revealed strong protein glycation inhibitory effects in C. sativum and S. aromaticum. C. zeylanicum showed a comparatively lower inhibition.

Open Access Original Research Article

Extractive Ion-Pair Spectrophotometric Assay of Amodiaquine

F. A. Onyegbule, C. J. Eboka, S. A. Adelusi

Journal of Pharmaceutical Research International, Page 313-321
DOI: 10.9734/BJPR/2015/15084

The quality of antimalaria drugs is a concern in malaria treatment and management. The quality of these drugs can be monitored and assured if simple, sensitive and accurate methods are available for routine use. Thus this extractive ion-pair spectrophotometric method was developed. Ion-pair was formed from equimolar concentration (10-4 M) of amodiaquine (5 ml) and bromocresol green (10 ml) in phthalate buffer (pH 5, 10 ml). The ion-pair was extracted into chloroform; re-extracted into 0.1 M sodium hydroxide; and determined spectrophotometrically. International Standard Requirements validation parameters were determined to evaluate the method applicability. The recovery data of the method was statistically compared with those obtained using nonaqueous titration. The extract absorbed maximally at 620 nm. The extract showed a stoichiometry of 1:2. Beer's law was obeyed in the concentration range of 1-50x 10-4 M of amodiaquine with good linearity (R> 0.99). A good accuracy was obtained from recovery studies. The extract was stable over 48 hours. The method complied with International Standard Requirements. The method compared positively with nonaqueous titration. Thus the method is good for amodiaquine analysis, with increased sensitivity from re-extraction into 0.1M sodium hydroxide. The method is simple; equipment and materials are readily available and no significant interference from common excipients.

Open Access Original Research Article

A Validated Bioanalytical Method for Quantification of Ziprasidone in Rabbit Plasma by LC-MS/MS: Application to a Pharmacokinetic Study

Khagga Bhavyasri, V. Murali Balaram, R. Nageswarao, D. Rambabu, M. Ajitha, Bala Sekhara Reddy Challa

Journal of Pharmaceutical Research International, Page 322-332
DOI: 10.9734/BJPR/2015/12137

A Liquid-liquid extraction method was developed for quantification of Ziprasidone in Rabbit plasma by a suitable bio-analytical method with LC-MS/MS. Ziprasidone d8 was used as an internal standard for Ziprasidone. Hypurity C18, 150 x 4.6 mm, 5 µm column used for chromatographic separation of analyte followed by detection with mass spectrometry. The total run time was 4.0 minutes. The proposed method has been validated with the linear range of 0.05 – 200.00 ng/mL for Ziprasidone. The intra-run and inter-run precision values were within 0.625 to 0.947% and 2.182 to 3.198% for Ziprasidone. The overall recovery for Ziprasidone and Ziprasidone d8 was 92.57% and 95.70% respectively. This validated method was successfully applied into the pharmacokinetic study of Rabbit plasma.

Open Access Original Research Article

Antidiabetic Activity and Toxicity Evaluation of Aqueous Extracts of Spondias mombin and Costus afer on Wistar Rats

Moke Emuesiri Goodies, Ilodigwe Emeka Emmanuel, Okonta Jemefuna Matthew, Emudainohwo Joseph Oghenebrorie Tedwins, Ajaghaku Daniel Lotanna, Erhirhie Oghenesuvwe Earnest, Chinwuba Paul, Ahante Ejiroghene

Journal of Pharmaceutical Research International, Page 333-342
DOI: 10.9734/BJPR/2015/17519

Aims: To evaluate the antidiabetic efficacy of the aqueous extracts of Spondias mombin leaf and Costus afer stem, both individually and in combination ratios, as well as the acute and subchronic toxicities of the most effective antidiabetic combination ratio.
Study Design: Antidiabetic study was carried using diabetic animals grouped into seven of five animals each.
Place and Duration of Study: Department of Pharmacology and Toxicology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria, between May 2013 and June 2014.
Methodology: Alloxan-induced diabetic rats received 100, 200 and 400 mg/kg of the extracts orally; control groups received glibenclamide (5 mg/kg, oral) and normal saline. Blood glucose was measured 2-hourly for 6 hours and weekly for 28 days. The LD50 of both plants was estimated using the modified Lorke’s method.
Results: The toxicity of the 1:1 mixture on body weight, haematological indices (RBC, WBC, PCV, and haemoglobin), and liver enzymes (AST, ALT, and ALP) were assessed for 60 days. The aqueous extracts of Spondias mombin and Costus afer showed significant (p>0.05) hypoglycaemic effect, with the 1:1 ratio having the best antidiabetic effects among the ratios when co-administered. There were non-significant (p>0.05) variations in weight change, RBC, WBC, PCV, and hemoglobin concentration, as well as in AST, ALT, and ALP levels of the test groups.
Conclusion: This study justifies the antidiabetic activity of the aqueous extracts of Spondias mombin and Costus afer, both individually and as mixtures of various ratios, especially when combined in equal proportions (1:1).

Open Access Original Research Article

Evaluation of Short Term Effect of Atorvastatin on Myocardial Performance and Its Pleiotropic Effects on Ischemic Heart Failure

Alaa El-Sisi, Sahar K. Hegazy, Mahmoud K. Ahmed, Manal A. Hamouda

Journal of Pharmaceutical Research International, Page 343-357
DOI: 10.9734/BJPR/2015/17441

Background: statins are used routinely in patients with coronary artery disease for their lipid lowering effects. Some clinical studies have found that statins do not affect clinical outcomes in patients with chronic heart failure (CHF), while others have found that statins have many beneficial effects. The aim of this study was to evaluate the pleiotropic effects of atorvastatin on patients with chronic heart failure of ischemic etiology (IHF) using conventional echocardiography and tissue doppler imaging.
Patient & Methods: Forty-eight patients with (CHF) were divided randomly into two equal groups; Atorvastatin group (received conventional therapy of HF plus atorvastatin 20 mg/d orally) and Control group (received conventional therapy only) for 3 months. Patients were examined both before and after treatment for biochemical tests; serum tumor necrosis factor α (TNF-α), serum high sensetive c reactive protein (hs-CRP), oxidized low density lipoprotein (ox- LDL), noradrenaline, adrenaline, renin, brain naturetic peptide (BNP-32), Troponin-I, total lipid profile and malondialdehyde. Conventional Echocardiography including left ventricle (LV) dimensions & wall thickness, ejection fraction (EF), E/A ratio, and tissue Doppler imaging (TDI) including Isovolumic contraction (IC), mitral annulus systolic velocity(S-peak), early (E) and late (A) diastolic peak velocities and Tei index were performed.
Results: Atorvastatin group showed statistically significant decreased in TNF- α, hs-CRP, ox-LDL, BNP-32 and noradrenaline compared to their baseline values before the study. Conventional echo failed to detect significant changes in each group except for significant increase in E/A ratio in atorvastatin group. DTI demonstrated that atorvastatin group showed significant improvement in systolic function [significant increase in S wave & isovolumic contraction (IC) peak velocities and better diastolic function [E peak velocity increased & E/E' ratio decreased significantly]. Tei index and heart rate improved significantly in atorvastatin group.
Conclusion: Atorvastatin improved cardiac function, decreased inflammatory and oxidative stress parameters as well as modulated the neurohormonal imbalance in CHF patients.

Open Access Original Research Article

Acetyl and Butyrylcholinesterase Inhibiting Constituent from Morinda lucida Benth (Rubiaceae)

Taiwo Olayemi Elufioye, Efere Obuotor, Joseph Morounfolu Agbedahunsi, Saburi Adejimi Adesanya

Journal of Pharmaceutical Research International, Page 358-365
DOI: 10.9734/BJPR/2015/16491

Aims: This study identified the cholinesterase inhibitory principle in Morinda lucida, one of the plants used in Nigerian ethnomedicine as memory enhancer.
Study Design: In vitro anti cholinesterase assay and spectroscopic analysis of isolated compound.
Place and Duration of Study: Department of Pharmacognosy, Obafemi Awolowo University, Nigeria between 2010 and 2012.
Methodology: Activity directed phytochemical analysis using Thin Layer Chromatography (TLC) bioautographic assay and repeated Vacuum Liquid Chromatography followed by Preparative Thin Layer Chromatography (PTLC) on silica gel was used to isolate one compound from the most active fraction of the plant.
Results: Spectroscopic analysis (Hand 13C NMR) and comparison with literature data identified this compound as phytol (3, 7, 11, 15-tetra methyl- 2-hexadecen-1-ol), with an IC50 of 12.93 µg/ml acetyl cholinesterase (AChE) and 24.90 µg/mlbutyryl cholinesterase (BuChE).
Conclusion: Isolation of compound with cholinesterase inhibitory activity has to some extent validated the ethnomedical use of the plant as memory enhancer and has provided new information on the chemistry of the plant.