Open Access Original Research Article

Comparative Effects of Antidiabetic Drug, Metformin and Deferoxamine, on the Hepatotoxic and Nephrotoxic Side Effects of Streptozotocin-induced Diabetes Mellitus in Rats

P. O. Okonkwo, Z. S. C. Okoye

Journal of Pharmaceutical Research International, Page 1820-1832
DOI: 10.9734/BJPR/2014/11812

Aims: The present study compared the effects of metformin (met) and deferoxamine (DFX) on the hepatotoxic and nephrotoxic side effects of streptozotocin experimental diabetes in rats using serum biochemical and histopathological indicators.
Study Design: Following induction of diabetes, animals were randomly and evenly distributed into four groups A, B, C and D of six rats each (n=6). Experimental diabetes was induced in overnight fasted rats by a single dose i.p each of nicotinamide and, 15min after, STZ followed by administration of the antidiabetic drug, met (os, 250mg/kgb.wt) and iron chelating drug, DFX (i.p,150mg/kgb.wt), daily for 14 days. Blood and histological samples were collected and prepared for biochemical and histopathological analysis of indicators of cytotoxic side effects.
Results: STZ caused cytotoxic effects on the liver and kidney of experimental rats, indicative of cellular leakage and loss of the functional integrity of the cell membranes. Metformin and deferoxamine both effectively reversed the hepatotoxic side effects of STZ-induced diabetes as determined by serum activities of ALP, AST and ALT and histopathological presentation. However, whereas metformin effectively reversed the STZ induced side effects on the kidney as determined by serum creatinine level and histopathological indicators, DFX did not.
Conclusion: It is concluded that metformin has a markedly higher potency than DFX in mitigation of hepatic and renal tissue derangement, as determined by both serum biomarkers and tissue histology.

Open Access Original Research Article

Erythropoietic Effects of Eremomastax polysperma Leaf Extracts on Female Prepubertal and Pubertal Wistar Rats

O. E. Mboso, M. O. Odey, F. E. Uboh, N. M. Essien, O. Chidinma, E. U. Eyong

Journal of Pharmaceutical Research International, Page 1833-1839
DOI: 10.9734/BJPR/2014/9603

This study assessed the erythropoietic effect of Eremomastax polysperma leaf extracts in female albino Wistar rats. Method: Twenty eight (28) female rats were divided into two major groups based on their weight and age. The duration of administration of E. polysperma extracts lasted for twenty one (21) days. This study was carried out in the Department of Biochemistry University of Calabar, between February and March 2013. A significant increase (P<0.05) in red blood cell count (RBC) (8.17±0.48, 6.46±0.37) and Haemoglobin (Hb) count (15.13±1.03, 13.27±0.7) was observed in the prepubertal group compared to the control, while packed cell volume (PCV) was significantly increased (P<0.05) in the pubertal group compared to the control (55.40±4.40, 48.63±2.33 respectively). This suggests that E. polysperma leaf extract can be used as a haematinic and a therapy for anaemic conditions.

Open Access Original Research Article

Potential Interactions of Herbal Extracts of St. John´s Wort with Metabolites of Diazepam in an Organotypical Sandwich Culture of Primary Porcine Hepatocytes

Ali Acikgöz, Angelika Langsch, Augustinus Bader, Shibashish Giri

Journal of Pharmaceutical Research International, Page 1840-1860
DOI: 10.9734/BJPR/2014/9602

Extracts of St. John’s Wort (Hypericum perforatum) are known to cause interactions with certain conventional drugs. Herein, we focus on two clinically relevant concepts. First, St. John´s Wort has been used by people of all ages as an herbal treatment for depression without medical prescription. Second, diazepam-like substances called endogenous benzodiazepines are found in cases of acute liver failure without previous exposure to diazepam. Currently diazepam has over 500 brands name and well marketed throughout the world and became one most frequently prescribed medication in different form (oral, injectable, inhalation and rectal forms) for four decades. Based on this concept, we investigated diazepam biotransformation by incubation of a widely accepted in vitro organotypical culture model with Hypericum methanolic extract, powdered drug, infusion, oil, and with the pure Hypericum compounds hyperforin and hypericin. The amounts of the preparations and compounds were chosen according to the recommended daily medication doses. We measured the activities of ethoxyresorufin-O-deethylase (EROD), ethoxy coumarin O-deethylase (ECOD) and the potential induction of diazepam metabolites (desmethyldiazepam, temazepam and oxazepam) during biotransformation. None of the preparations or substances induced EROD or ECOD. However, different preparations did induce the formation of desmethyldiazepam and temazepam. The strongest activity was caused by the extract, followed by the powdered drug and hyperforin. All preparations and compounds increased the formation of the diazepam metabolite oxazepam, but only the extract, the drug powder and the pure compounds had marked effects. Therefore, we report here the potential interference of St. John´s Wort with all three metabolites of diazepam in an organotypical sandwich model that can be utilized to study potential interaction of metabolites of many drugs with herbal ingredients in preclinical stage of drug discovery process.

Open Access Original Research Article

In vitro- In vivo Correlation Studies of Modified Release Tolterodine Tablet Dosage form in Rabbits

P. Srinivasa Babu, S. K. Rihana Parveen, K. B. Chandrasekar, B. R. Challa

Journal of Pharmaceutical Research International, Page 1861-1872
DOI: 10.9734/BJPR/2014/9950

Tolterodine is an antimuscarnic drug that is used for sympathetic treatment of urinary incontinence. Tolterodine modified release tablet, was investigated in rabbit for pharmacokinetic and in vitro–in vivocorrelation studies. Tablets were prepared and in vitro release was studied in simulated gastric fluid at 150RPMs. New Zealand albino male rabbits have been used as animal model for in vivo study. A sensitive and simple HPLC method was developed for the determination of Tolterodine content in rabbit plasma. In vitro release studies showed that release patterns followed zero order for around 24h. The in vivo–in vitro correlation coefficients obtained from point-to-point analysis were greater than 99% between concentrations at certain time points obtained from release study in simulated gastric fluid and HPLC analysis of rabbit’s plasma.
From the in vitro–in vivo correlation prediction it was evident that the Tolterodine matrix assisted tablet is a good for controlled delivery of Tolterodine.

Open Access Original Research Article

Iodine-125-Chlorambucil as Possible Radio Anticancer for Diagnosis and Therapy of Cancer: Preparation and Tissue Distribution

A. M. Amin, N. S. Farrag, A. AbdEl-Bary

Journal of Pharmaceutical Research International, Page 1873-1885
DOI: 10.9734/BJPR/2014/10520

Chlorambucil (CLB) is an aromatic nitrogen mustard and an alkylating agent. It has been mainly used in the chemotherapy. A method for radiopharmaceutical preparation of [125I]-iodo-Chlorambucil a potential cancer therapeutic agent is described. The method is based on direct electrophilic radioiodination of Chlorambucil with [125I] in the presence of chloramine-T (CAT) as oxidizing agent. The reaction conditions were optimized in order to obtain a radiochemical yield higher than 98% of [125I]-iodo chlorambucil. Different chromatographic techniques (electrophoresis, and high pressure liquid chromatography (HPLC)) were used to evaluate the radiochemical yield and purity of the labeled product. Biodistribution studies of 125I- chlorambucil were carried out in both normal and tumor bearing Albino Swiss mice. The results revealed that this new tracer, 125I-chlorambucil, has a high affinity to be localized in the tumor site for a long period which indicates the specificity of this tracer to the tumor cells. The results indicate the possibility of using [125I]-iodo chlorambucil for imaging and treatment of cancer.

Open Access Original Research Article

The Role of Losartan and Oral Magnesium Sulfate in Cisplatin Induced Nephrotoxicity in Female Rats

Farzaneh Razmjoo, Nepton Soltani, Mehdi Nematbakhsh, Ardeshir Talebi, Fatemeh Eshraghi-Jazi, Mansooreh Ghayyomi

Journal of Pharmaceutical Research International, Page 1886-1899
DOI: 10.9734/BJPR/2014/10164

Hypomagnesemia is one of the nephrotoxicity signs. In addition, renin-angiotensin system may be involved in pathophysiology of kidney diseases. Therefore, the present study was designed to investigate the possible role of losartan plus oral magnesium sulfate (MgSO4) to reduce CP-induced nephrotoxicity in female rats. The animals were divided into twelve groups: Group 1-6 received saline, MgSO4 (3g/l), MgSO4(10g/l), losartan, MgSO4 (3g/l) plus losartan, MgSO4 (10g/l) plus losartan, respectively. The animals received MgSO4 via drinking water for 9 days. In addition, losartan (10mg/kg/day; i. p.) was accompanied with MgSO4from day 3. Groups 7-12 followed the same regimen of above groups, but CP (2.5mg/kg/day; i. p.) was added to regimen from day 3. At the end of day 9, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were measured. The kidneys were removed rapidly for histopathological study. The Co-administration of losartan and MgSO4 (3g/l) decreased serum Cr and BUN levels in CP treated animals. Also, that was partially attenuated the kidney tissue damage. It was concluded that combination of losartan and MgSO4 (3g/l) may ameliorate kidney function against CP-induced failure.

Open Access Original Research Article

Acute Toxicity of Chloroform Extract of Artemisia macivera Linn in Swiss Albino Mice

A. C. Ene, S. E. Atawodi, M. Y. Fatihu

Journal of Pharmaceutical Research International, Page 1900-1908
DOI: 10.9734/BJPR/2014/7865

The acute toxicity of chloroform extract of Artemisia maciverae Linn was studied in Swiss albino mice. The mice were randomly distributed into four groups of three animals each. The groups were respectively administered both intraperitoneally and orally chloroform extract of Artemisia maciverae at 0, 10, 100 and 1000mg/kg in a single dose and monitored frequently for 24h and daily for 13 days in the first phase of the experiment. In the second phase of the experiment, the animals were administered single doses of the extract at 0, 200, 400 and 800mg/kg both intraperitoneally and orally and monitored frequently for 24h and 13 days respectively. The number of deaths in a group was recorded. The results of the second phase experiment were used to calculate the LD50 of the plant extract. All surviving animals were sacrificed after 14 days. Selected organs of the animals i.e. heart, lungs, liver, kidney, spleen, stomach and intestine of both the dead and sacrificed animals were removed and stored in 10% formal saline ready for histopathological analysis. Tissue specimens of the organs were examined histopathologically after processing and staining with haematoxylin and eosin. Lesions were observed in the liver, kidney and intestine of mice administered 800 and 1000mg/kg of chloroform extract of Artemisia maciverae. From this result, the LD50 of the chloroform extract of Artemisia maciverae was calculated to be 566 mg/kg. The results indicate that the extract may be toxic at a high dose and short term exposure.

Open Access Original Research Article

Development of a Validated HPLC Method for the Estimation of Metformin HCl and Propranolol HCl

Venkata Srikanth Meka, Janaki Ram Battu, Senthil Rajan Dharmalingam, Adinarayana Gorajana, Venkata Ramana Murthy Kolapalli

Journal of Pharmaceutical Research International, Page 1909-1922
DOI: 10.9734/BJPR/2014/10826

The present investigation targets to develop a simple, specific, sensitive and accurate reverse phase high performance liquid chromatographic (RP-HPLC) method in human plasma for the estimation of metformin HCl and propranolol HCl from bulk drug and also from the marketed products. Human plasma samples were subjected to correct procedure for protein precipitation by methanol and protein free plasma samples were directly injected into HPLC C18 column. Chromatographic determination was performed on a reversed phase C18 column (3.9 mm X 300 mm, particle size 5 µm) using a mixture of acetonitrile and 0.1M pH 4.5 potassium dihydrogenortho phosphate buffer (mL) (40:60) at a flow rate of 0.8 mL/min and maintained at a pressure of 140 to 150 Kg/cm2. The retention time for metformin HCl and propranolol HCl was found to be 9.084 min and 6.132 min respectively at 232 nm without any interference of endogenous compounds in the plasma. The method was linear in the range between 50-2000 ng/mL. The peak areas were reproducible as indicated by low coefficient of variation. It was found that the excipients in the tablet dosage form do not interfere in the quantification of active drug by proposed method.