Iranian Journal of Pharmaceutical Research
Year:2008 | Volume:7 | Issue:1|Papers Count:12

Importance of toxicology: Toxicology is the study of how chemical substances interact with living systems, affecting normal processes, and the use of this information to predict safe exposure levels. The goal of toxicity testing is to insure safety of chemicals (or societally tolerable level of risk) in exposed human populations, although no substance is risk-free. Toxicological testing of new materials, as well as biosafety measurement of existing components, helps us to live safely and to derive benefit from natural and synthetic substances while avoiding toxic substances. Toxicologists are involved in the evaluation of household products, medicines and the effects of incidental and occupational exposure to natural and manufactured substances. Toxicology also assists us to develop the best management in the event of accidental overexposure. One fundamental tenet of the science of toxicology is that all chemicals can be toxic if administered in special doses. This is mentioned as a famous phrase: "The dose makes the poison"(1). During the industrial processes there is a chance some of product contamination due to unwanted materials. Hence, conduction of routine biosafety investigation by most of food and drug agencies is required. Although in Iran progress in the field of toxicology is noticeable, considering the numerous international publications and organization of several domestic and international scientific onferences, as well as the establishment toxicology research centers, we experience difficulties in the field of industrial regulatory toxicology and animal studies. In the clinical section, we have two professional hospitals and few physicians, which comply with the standard procedures of emergency medicine.

Natural substances extracted from plants have recently been considered as potential sunscreen resources because of their ultraviolet ray absorption in the UVA region and their antioxidant activity. In the present study, the UV protective effects of ethyl acetate extracts of some common medicinal plants, which have flavonoids and other phenolics as the most important components, were evaluated using diffuse transmittance method and calculating Sun Protection Factors (SPFs). The ethyl acetate extracts of sixteen medicinal plants were analyzed for their in vitro SPF by measurement of their transmittance at different concentrations in methanol. Extracts of leaves of Dracocephalum moldavica L. (Lamiaceae) and flowering tops of Violatricolor L. (Violaceae) had the highest SPFs, i.e.24.79 and 25.69, respectively. D. moldavica and V. tricolor had high amounts of phenolic compounds and flavonoids., which could be the cause for their high SPF.

Nanoparticles made of biodegradable polymers have become the best approach for nanoparticle making due to their compatibility with the human body.New glycerol cidipate polymers with hydroxyl group substituted with different percent of acyl group, sited as figures within the abbreviated name in the text, and triptophan were synthesized and proposed to be used in the preparction of dexamethason phosphate loaded nanoparticles, using the evaporation-deposition technique. The particle forming ability, size and distribution of the nanoparticles might be related to more important physicochemical characteristics, such as the surface properties of the polymers.In this study surface free energies of five derivatives (0%, 20%, 40%, 100% and triptophan 5%) were determined by means of contact angle measurement carried out on films formed on the glass slides KSC Cam 100 instrument. The results were then incorporated into the Fowkes equation, toobtion the surface energy of the polymers. Also, different concentrations of methanol were used to obtion contact angles, which in turn were used to give the critical surface tension (gc) of the polymers, using the Zizman's method.The results of surface characteristics indicated that the 40% C8 polymer was probably the most consistent, compared to the others during the preparation stage, in order to form smaller sized particles with a narrower distribution, correlating with the other works carried out on the loaded particles.In conclusion, it seems that this method could be used to predict characteristics of polymers used for the selection of the best polymer in this series and probably other polymers for nanoparticle making, particularly for the loading of ionized drugs.

Silver ion has been used for centuriesto prevent and treat a variety of diseases and infections. In recent years, extensive studies have been undertaken on the use of antimicrobial properties of silver, incorporated within medical devices. The aim of this study was to prepare a formulation containing silver ion, which could be applied for wound dressing. The purity of nanosilver was measured by atomic absorption spectrophotometer. The purity was determined to be 96.80%±0.01. The "serial dilution method" was used to determine the Minimum Inhibitory Concentration (MIC) of nanosilver, on microorganisms such as staphylococcus aureus, and Pseudomonas aeruginosa. The MIC of nanosilver solution was 15.12 mg/ml. In order to design a hydrogel formulation, different formulations, using HPMC K15M, were made. Next, the best formulation (at 2% w/w) was selected, based on attractiveness, homogeneity and flexibility. This formulation was used for the preparation of the next formulations, containing various percentages of two types of plasticizer. Again, the best formulation was chosen. In order to increase the thickness and resistance of the film, another polymer (HPMC K100 or agar), was added to the formulation. For evaluation of the prepared films, different tests including determination of thickness and tensile strength, swelling and water vapor transition were performed. Finally, the best formulation containing 2% w/w HPMC K15M, 0.5% w/w HPMCK 100 and 0.2% triacetin (as plasticizer) was selected. Then, various concentrations of nanosilver solution were added to the selected formulation. In this manner, the most suitable concentration of nanosilver (4 mg in an area of 100cm2 or almost 1.5 g weight), which had the best antimicrobial effect in the hydrogel films was detected. In the final stage, the amount of silver in the final film was determined by atomic absorption spectrophotometer. The obtained result confirmed the amount of silver in the final film.

Moclobemide is a selective and reversible monoamine oxidase-A inhibitor, which is used as an antidepressant. Three moclobemide analogues were synthesized by replacing moclobemide phenyl ring with substituted imidazoles, So, N-[(4-morpholinyl) ethyl)]-I-benzyl-2-(alkylthio)- IH-imidazole-5-carboxamides (7a-c) were synthesized and studied for the antidepressant activityusing forced swimming test in mice. Analogues 7a-c were found to be more potent than moclobemide. Minimum effective doses for moclobemide and analogues 7a-c were found to be 20, 2.5, 1.25 and 2.5 mg/kg i.p. respectively. 

In this study the role of glutathione (GSH) in sulfur mustard -induced oxidative stress and cytotoxicity, in human skin fibroblast cell line (HF2FF) was evaluated. Sulfur mustard induced superoxide radical and hydrogen peroxide formation were evaluated by determination of superoxide dismutase and catalase activity in cell lysate. The cytotoxicity of sulfur mustard was estimated by lactate dehydrogenase leakage. The intracellular GSH content was modulated by N-acetylcysteine (NAC), a GSH precursor, and buthionine sulfoximine (BSO), a specific GSH synthesis inhibitor. It was found that sulfur mustard exposure led to a dose-and time-dependent decrease in GSH content inHF2FF cells.NAC increased intracellular GSH level and protected the cells against sulfur mustard-induced reactive oxygen species formation and lactate dehydrogenase leakage. In contrast, buthionine sulfoximine pretreatment depleted cellular GSH and enhanced the susceptibility of HF2FF to the cytotoxic effects of sulfur mustard. These results indicated that GSH plays a critical role in protecting HF2FF cell line against sulfur mustar-induced cell injury, most probably through its antioxidant activity.

Lead (Pb2+) is a well known neurotoxin that was frequently found in the environment and chronic exposure to lead has been matter of public health. In the present study the effect of lead on spatial memory in developmentally exposed rats and their dams in Morris water maze task were investigated. Female rats were divided into three groups and two groups exposed to 250 and 750 part per million (ppm) Pb acetate and one group Na acetate, as a control group, through drinking water, ten days prior to mating and continue through pregnancy, pregnant animals were tested in the swim task at gestation day 14±2. Another group of animals exposed to the same concentration of Pb acetate at different developmental stages including a maternally exposed group (including gestation and lactation period) and continuously exposed group (including gestation, lactation and continue to lead exposure until test time). Rats in these groups were tested for spatial learning and memory in Morris water maze task at post natal day (PND) 56.Exposure to lead did not affect learning ability of dams in Morris water maze performance indicating by no significant differences in escape latency and traveled distance between groups, but, for both maternally-and continuously-exposed groups treated with 750 ppm lead, average escapelatency and traveled distance were increased, indicating significant impairment in spatial learning and memory. These results are more direct evidence that indicate developing brain is more susceptible to Pb2+induced neurotoxicity.

The aim of this study was to investigate the effects of ethanolic extract of the whole plant of Phyllanthus rheedii wight P.rheedii as antihyperglycemic, antihyperlipidemic and antioxidant effect in streptozotocin (STZ) induced diabetic rats. Male Wistar rats were administered P.rheedii (250 mg/kg) orally for 21 days and blood glucose level was measured weekly. At the end of 21 days, the serum lipid metabolites such as total cholesterol, triglycerides, high density lipoproteins (HDL) and protein metabolites such as total protein, albumin, globulin and albumin:globulin ratio (A:G) enzyme level viz serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) were determined. In order to determine antioxidant activity of extract, liver tissues were homogenized in ice cold saline buffer and the assay of lipid peroxides (LPO), superoxide dismutase (SOD) and catalase (CAT) were performed in control, STZ and extract treated rats. All these effects were compared with glibenclamide as a reference antidiabetic drug. Oral administration of P.rheedii for 21 days resulted in a significant reduction in blood glucose level, lipid metabolism and enzymes level and significant improvement in LPO, SOD and catalase in liver tissues of STZ induced diabetic rats when compared with untreated diabetic rats. The protein metabolites were significantly altered near to normal. The effects produced by the extract were comparable to that of glibenclamide.In conclusion The P.rheedii showed significant antihyperglycemic, antihyperlipidemic and antioxidants effect in STZ induced diabetic rats.

Diabetes mellitus is a metabolic disorder affecting carbohydrate, fat and protein metabolism that affects nearly 10% of the population every year. The treatment of diabetes mellitus has been confined to use of oral hypoglycemic agents and insulin, the former being reported to possess seriousside effects. This leads to increasing demand for herbal products with antidiabetic factor with little side effects.This article describes the antihyperglycaemic activity, in vivo antioxidant potential, effect on glycosylation of hemoglobin and in-vitro peripheral utilisation of glucose of the ethanolic extract of the aerial parts of Bacopa monnieri. The extract produced significant decrease in the blood glucose level when compared with the controls in alloxan induced hyperglycemic rats both in the single dose as well as multiple dose experiment at the tested dose level and is comparable with the standard drug glibenclamide. It was observed that the ethanolic extract reversed the weight loss of the diabetic rats and they returned to near normal. The extract prevented significant elevation of glycosylated hemoglobin in vitro, with IC50 value being 11.25 mg/ml that is comparable with the reference drug a-tocopherol. Administration of the exract and glibenclamide significantly decreased the levels of TBARS, increased the content of GSH and increased the activity of SOD and CAT in liver of diabetic rats. The extract increased peripheral glucose utilisation in the diaphragm of diabetic rats in vitro, which is comparable with the action of insulin. Thus, the extract might have insulin like activity and the antihyperglycemic effect of the extract might be due to an increase in peripheral glucose consumption as well as protection against oxidative damage in alloxanised diabetes.

The increasing incidence of candidiasis and antifungal resistance as well as the introducing of new antifungal has recently encouraged performing of fungal susceptibility testing. The aim of this study was to evaluate the susceptibility profile of Candida species isolated from patients admitted to Yazd central laboratory to fluconazole. We used the broth microdilution method to evaluate the susceptibility profile of a large collection of recent clinical Candida isolates, recovered from patients' specimens, against fluconazole. Totally 462 yeast isolates were analyzed, including the following species: 284 isolates of Candida albicans, 69 isolates of C. tropicalis, 41 isolates of C. parapsilosis, 31 isolates of C. glabrata, 14 isolates of C. krusei, 11 isolates of C. guilliermondii and 10 isolates of Candida kefyr and 2 other yeasts. Susceptibility ranking to fluconazole obtained by all tested yeasts was: C. tropicalis>C. albicans>C. parapsilosi> C. kefyr>C. guilliermondii>C. glabrata>C.krusei. The majority (81%) of all tested yeast isolates were susceptible to fluconazole. There were seen statistical significant differences between the MIC of all isolates (p<0.05). Isolates of C. glabrata and C. krusei showed the highest rate of broth microdilution resistance among all tested isolates, but these only species represented 11.6% of all yeasts isolated from specimens in Yazd central laboratory. In order to identify any changes in the susceptibility patterns of fluconazole with the increased use of this antifungal agent, careful periodical surveillance testing was needed.

Drug utilization evaluation (DUE) is an effective program to identify variability in drug use and to support interventions that will improve patient outcomes. The appropriate use of enoxaparin, a low molecular weight heparin (LMWH), which is widely used as curative or preventive treatment of thromboembolic disorders was assessed in the study.A prospective DUE was carried out at Masih Daneshvari teaching hospital. Criteria for the appropriate use of enoxaparin were used to evaluate prescription and administration patterns in this hospital.Enoxaparin utilization of 147 inpatients was reviewed. A total of 944 variables (70.92%) in the regimen, among all subjects, were rated as appropriate and 382 (28.70%) were rated as inappropriate for the conditions diagnosed.The results of this study showed that inappropriate dosing, administration and prescribing of enoxaparin is rather common in masih hospital. Educational programs and implementation of protocols may be needed in the teaching hospitals to control prescribing patterns.

Due to a narrow therapeutic range, measurement of theophylline serum levels is highly recommended in patients with a long-term theophylline therapy. In this regard, since blood sampling is an invasive method, exploring alternative methods using other biological fluids in particular saliva samples are targeted. This study was designed to determine any relationship between serum and saliva levels of theophylline in patients with asthma and COPD, whom have been under xanthine-therapy for an extended period of time. Also, any relationship between serum or saliva levels of theophylline with possible explanatory factors was investigated. Adult (2:18 years) outpatients with a history of theophylline use (for at least 1month) entered this study. Serum and stimulated saliva samples obtained 1 h before the morning dose and were measured using a high performance liquid chromatography (HPLC) method. To stimulate saliva production, patients chewed a piece of parafilm for 5 min before sampling. Relevant demographic information, medical and medication histories of the patients were also recorded. Collected data were entered into the SPSS (Statistical Package for Social Scientists, version 11.5) software and analyzed using the appropriate statistical tests (p<0.05). Eighty-six patients (44 males and 42 females) with a mean±SD age of 58.72±14.23 years enrolled in the study. Mean±SD of serum and saliva concentrations of theophylline were 5.4±2.8 mcg/ml and 4.0±2.1mcg/ml, respectively. Forty five patients (52.3%) had subtherapeutic serum levels of less than 5 mcg/ml. There was a significant direct relationship between serum and saliva levels of theophylline (p=0.0001, r=0.91). Multivariate analysis led to a model in which only total daily dose of theophylline (mg) could remain as a predictor associated with the serum (p=0.0002, r=0.53) and saliva levels (p=0.0001, r=0.47).Aconsiderable association observed between serum and saliva levels of theophylline, confirms previous reports. The observed high frequency of the patients with sub therapeutic serum levels emphasizes the importance of implementing therapeutic drug monitoring (TDM) of theophylline in patients with a long-term theophylline therapy, using non-invasive alternative sampling methods e.g. saliva sampling.