Iranian Journal of Pharmaceutical Sciences
Volume:6 Issue: 2, Spring 2010

Dendrimer based nanostructures have been increasingly used for delivery of drugs/genes. These nanosystems, as non-viral gene delivery systems, were shown to have relatively high transfection efficiency despite exerting somewhat cytotoxicity. In this current investigation, poly(amido amine) (PAMAM) dendrimers, generation  (G) zero to five, PEGylated PAMAM G3 and a new quaternized PAMAM G4 were synthesized and further characterized using FT-IR and 1H-NMR spectroscopies. The cellular uptakes and toxicity of these nanosystems were investigated using fluorescence microscopy and MTT assay, at which they revealed high internaliza-tion potential with low cytotoxicity in both T47D and MCF-7 cells. To establish a simple detection methodology, a ninhydrin reaction was performed on intact PAMAM full generations as well as PEGylated PAMAM G3 and quaternized PAMAM G4. Impacts of various factors such as reaction time, kinetic, reaction medium, and generation dependency of the reaction of dendrimers with ninhydrin were investigated. The best reaction conditions were determined and a simple and reproducible spectroscopic method was established. Upon these findings, we propose that this ninhydrin reaction based methodology may be considered as an easy approach for quantification of primary amines of nanostructured PAMAM dendrimer and its derivatives.

Propranolol, a prototypical b-adrenergic receptor antagonist and atenolol, a cardio-selective b-antagonist are widely used in therapeutic regimens for treatment of hypertensive patients. In Iran, several pharmaceutical manufacturers formulate these two b-blockers. As the formulation of a dosage form is essential for the patient's safety and drug efficacy, in this study we aimed to evaluate the quality of the tablets which are formulated by the above manufacturers. Atenolol (100 mg) tablet manufactured by APOTEX in Canada also was evaluated. The commercially available preparations of the following dosage forms were studied: propranolol (10 mg, 40 mg) manufactured by TOLID DARU and ROSE DARU (a, b, c, d), atenolol (50 mg) manufactured by DARUPAKHSH (e), atenolol (100 mg) manufactured by DARUPAKHSH, TOLID DARU, SOBHAN, LORESTAN and APOTEX (f, g, h, i, j). The quality and safety of the dosage forms of these drugs were evaluated by PMS studies. For this purpose, the weight variation, hardness, thickness, content assay, content uniformity, disintegration time and dissolution rate of the dosage forms were compared to British Pharmacopeia (BP) and United States Pharmacopeia (USP) standards. The results verify that all dosage forms show evidence of the USP and BP quality assessment.

Doxorubicin (DOX) is an anthracycline antibiotic that has been used for a long time in therapy of an array of human malignancies either alone or in combination with other cytotoxic agents. The dose-dependent cardiotoxicity of DOX significantly limits its anticancer efficacies. Oxidative stress caused by enhanced production of reactive oxygen species is an important contributor to DOX mitochondrial toxicity. In the present study, DOX produced a significant elevation in TBARS, which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase in rat liver mitochondria. Mitochondrial GSH dramatically decreased while GSSG was increased upon treatment of mitochondria by DOX. Co-treatment with captopril significantly reduced the lipid peroxidation in mitochondria and prevented the inhibition of superoxide dismutase activity induced by DOX. Captopril also significantly increased the level of GSH in DOX-treated mitochondria. These results, therefore, suggest that captopril acts as an antioxidant and can protect the mitochondria against DOX-induced oxidative stress. This effect appears to be due to the sulfhydryl groups of captopril which may act as antioxidant or scavenger of reactive oxygen species.

This study was designed to explore the protective effects of Abrus precatorius L. (Leguminosae) (AP) in HepG2 cells and N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in Swiss albino rats. The effects of aqueous/ethanolic (50%) extract of AP on hepatic markers, haematological and histopathological parameters, and antioxidant enzymes were evaluated in NDEA (200 mg/kg and CCl4, 3 ml/kg body weight) induced experimental hepatocarcinogenesis in Swiss albino rats. In addition, cytotoxicity of the extract and its effect on the expression on p53 were studied in human hepatoma cell line (HepG2). Results obtained from cytotoxicity studies showed that the AP extract has strong cytotoxic effects on HepG2 cells. The expression of p53 was markedly increased and maintained at high level from 6-12 hr with 100 µg/ml of AP extract. A decrease in the mean and relative liver weights in AP extract treated group at a dose of 100 and 200 mg/kg was observed compared to the control group. It was also demonstrated that AP extract provided significant protection against hepatic lipid peroxidation and increased antioxidant enzymes’ activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reduced glutathione levels. In a dose-dependent manner, the AP extract reduced the NDEA-induced elevated levels of various hepatic markers such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total bilirubin and gamma glutamate transpeptidase. The haematological paremater viz. RBC, WBC and haemaglobin was restored upon treatment with AP extract at 100 and 200 mg/kg. Histopathology of the liver was also carried out to mark the pathological changes in groups under study. The results of these studies demonstrate the protective effect of AP extract against NDEA induced hepatocarcinogenesis in Swiss albino rats and in HepG2 cell.

Many studies have proved that the dietary micronutrient has an inhibitory effect against experimentally induced rat hepatocarcinogenesis. The present work is an attempt to understand combined effect of selenium (Se) and vitamin D3 (vit D3) on some potential protein expression markers of carcinogenesis, such as metallothionein (MT), P53 and antioxidant levels during diethyl nitrosamine (DEN) induced (200 mg/kg in 0.9% NaCl; IP) rat liv er preneoplasia. In a short term regimen combined supplementation of Se and vit D3 at a dose of 8 ppm in water and 0.3 μl/100μl in propylene glycol, respectively, suppressed the formation of DNA comets (28.40%), thereby indicating its non- genotoxicity at this particular dose. Se and vit D3 administration throughout the study reduced relative liver weight. Modular incidence were 22.7% when compared to the carcinogen control. However, treatment with Se and vit D3 showed significant expressions of MT and P53 which studied at four sequential time points. An increased immunopositive of P53 protein (1.3±0.56% p3 together treated rat liver with an elevated apoptotic labeling index (A1; p3 together mediated suppression of MT may be associated with induction of apoptosis. The results thus provide evidence for the first time in support of the potential role of combined supplementation of Se and vit D3 on induction of P53 apoptosis with concurrent suppression of MT in order to have an understanding. Regardless of the mechanism, based on the results reported in this study, both Se and vit D3 could be considered a potential cancer chemopreventive agents whose effect is presumably based on inhibition of growth of the neoplastic cells by coordinated regulations of different biochemical markers and enzymes studied herein.

Staphylococcus aureus is a major bacterial pathogen that causes different community- and hospital-acquired infections. Over time, strains of S. aureus have become resistant to different antibiotics including penicillinase-resistant penicillins. Having data on the local antimicrobial susceptibility pattern of this pathogen is necessary for selection of appropriate antibiotics for empirical treatment of infections due to it. To determine the antimicrobial susceptibility pattern of Staphylococcus aureus strains isolated from hospitalized patients in Tehran, Iran, In a prospective cross-sectional study performed at Imam Khomeini Hospital, samples were collected from hospitalized patients and were cultured. All positive cultures which yielded S. aureus underwent antimicrobial susceptibility testing using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar. The results were interpreted after 24 hours of incubation at 37 °C. A total of 160 clinical isolates of S. aureus were collected. Most isolates were obtained from blood (29%). The overall susceptibility of isolated S. aureus strains to antimicrobial agents was 100% for vancomycin, 49.4% for amikacin, 43.8% for gentamicin, 36.8% for co-trimoxazole and tetracycline, 36.3% for cefazolin, 30.6% for cephalexin, 24.4% for oxacillin, 23.8% for erythromycin, and 3.1% for penicillin. Other than vancomycin, none of the tested antibiotics are appropriate for empirical treatment of serious S .aureus infections in our area.

Butyl-hydroxytoluene (BHT) is one of the major synthetic antioxidants with a wide range usage. Replacement of artificial antioxidants with natural antioxidants is highly considered. In this research, the antioxidant activity of Juniperus excelsa was investigated by using reducing power, DPPH radical scavenging and inhibition of lipid peroxidation. Also, the amounts of phenolic and flavonoid compounds were determined. Ethanol extract of Juniperus excelsa was fractionated based on increasing the polarity. The reducing power of ethyl acetate fraction was more than butanol fraction. The IC50 of ethyl acetate fraction (204.3±12.8 µg/ml) was less than that of butanolic (>400 µg/ml) fraction (ppJuniperus excelsa, especially ethyl acetate, had more antioxidant activity.

Volatile constituents of the seed kernel and leaf of cultivated Moringa peregrina (Forssk.) Fiori, Agricolt collected after hydrolysis were analyzed by GC and GC/MS. Five glucosinolate degradation products which constituted almost the whole isolated oil of the seed kernel were identified to be: isobutyl isothiocyanate (94.0%), isopropyl isothiocyanate (4.9%), sec-butyl isothiocyanate (0.5%), n-butyl isothiocyanate(0.5%) and benzyl isothiocyanate (<0.1%); while the volatile isoth-iocyanates which constituted also almost the whole isolated oil of the leaf were found to be: isobutyl isothiocyanate (88.5%), isopropyl isothiocyanate (10.2%), n-butyl isothiocyanate (0.4%) and sec-butyl isothiocyanate (<0.1%).