PHARMACEUTICAL SCIENCES
Year:2018 | Volume:24 | Issue:2|Papers Count:12

Background: The study aims at the establishment of pharmacokinetic interaction between vasicine and salbutamol in low and high dose combinations on rabbits. Methods: Previously developed in vitro simultaneous estimation method of vasicine and salbutamol was further validated by recovery study in the spiked plasma sample. Pharmacokinetic interaction study was performed on the rabbit at 30 and 60 mg/kg vasicine administered with 2 and 4 mg/kg salbutamol orally based on literature reports. Vasicine and salbutamol were extracted from plasma up to 12 hr post drug administration, analyzed by HPLC and pharmacokinetic parameters were calculated. Results: HPLC co-analysis of vasicine and salbutamol in the spiked plasma samples showed recovery in the range of 92. 44 to 99. 14% and RSD less than 1%. Vasicine showed the limit of quantification 136 ng/ml with interday and intraday variation less than 1% indicating reproducibility. Co-administration of vasicine and salbutamol significantly (p < 0. 001) elevates elimination rate constant, decreases clearance, biological half-life and volume of distribution of salbutamol compared to administration alone. Salbutamol showed high (p < 0. 001) clearance and AUC value, whereas vasicine showed significantly high (p < 0. 01-0. 001) elimination rate constant, clearance, volume of distribution and AUC wh e n co-administered. Conclusions: Combined administration of vasicine and salbutamol has drastically increased the bioavailability of salbutamol though vasicine bioavailability was practically unchanged. This study signifies that concurrently administered salbutamol with vasicine can induce occurrence of serious life threatening adverse event may be due to additive vasodilatory effect.

Background: Nephrotoxicity is one of the most common renal problems that especially occur when the body is exposed to drugs or chemical reagents. Allium jesdianum Boiss is the largest and most important plants genus of onion family that possesses many pharmacological effects. The present study was undertaken to investigate the effect Allium jesdianum Boiss in the treatment of nephrotoxicity induced by carbon tetrachloride (CCl4). Methods: Forty two male mice were randomly divided into six groups; control, sham, CCl4 (1 ml/Kg, i. p) single dose, Allium (500, 1000 and 2000 mg/kg) + CCl4. Blood urea nitrogen (BUN) and serum creatinine (Cr) evaluated in serum. Glutathione (GSH), catalase (CAT), malondialdehyde (MDA) and reactive oxygen species (ROS) were analyzed in kidney tissue homogenate and done the microscopic studies of renal tissue. Results: The results indicated a significant increase of serum BUN and Cr as well as MDA and ROS levels and decrease of GSH and CAT in CCl4 treated mice when compared with the control group (p < 0. 001), whereas all studied endpoints were significantly altered in pretreatment with Allium extract when compared with CCl4 treated mice (p < 0. 001). Renal histopathology indicated normal appearances reduced in CCl4 treated mice and Allium extract administration improved changes in renal tissue. Conclusion: Administration of the hydroalcoholic extract of Allium jesdianum Boiss could prevent nephrotoxicity induced by CCl4. The protective potential may involve the powerful antioxidant of this plant by eliminating free radicals induced by CCl4.

Background: Cisplatin (Cis) is a chemotherapeutic agent and nephrotoxicity is a serious adverse effect of the drug. This study investigated the protective effects of Cornus mas fruit hydro-methanolic extract (CME) on cisplatin-induced nephrotoxicity in a rat model. Methods: Forty Wistar rats were divided into the control group, CME group, CME 300 + Cis group, CME 700 + Cis group, and Cis group. After the intervention samples were taken for biochemical and histopathological analysis. Results: The CME analysis showed considerable total antioxidant and total phenol contents. The blood serum urea and creatinine increased (p < 0. 01) in the Cis group rats. In the Cis + CME groups, the parameters were not significantly different from that of the control group. There were no significant differences in the renal activities of SOD, GPx, CAT, and TAC between the Cis-treated and control groups (p > 0. 05). The renal MDA levels of the Cis and CME 300 + Cis groups decreased significantly in comparison to the control and the CME groups (p < 0. 01 and p < 0. 05, respectively). In the histopathological examination, mild to severe degeneration was observed in the Cis group. Despite the presence of mild degeneration, they were less severe in the Cis + CME groups, and maintained a better morphology when compared to the Cis group (p < 0. 01). Conclusion: The results showed renoprotective effects of CME against Cis-induced nephrotoxicity in rats.

Background: Ceratonia silique has antioxidant activities that may inactivate toxic factors and influence sperm quality. To the best of the authors’ knowledge, there is no available data on the effects of carob on male fertility. Hence, the purpose of this study was to investigate the effects of carob on sperm quality, testicular structure, and level of testosterone hormone in busulfan-induced infertile mice. Methods: Sixty-four adult male mice were randomly divided into 8 groups (control, sham, busulfan and carobs 1 to 5). The busulfan group was injected a single dose of 10 mg/kg busulfan intraperitoneally. Carobs 1 to 5 groups received intraperitoneal doses of 800, 400, 200, 100 and 50 mg/kg of carob extract plus a single dose of 10 mg/kg busulfan for 35 days. The sperm analysis, morphometric study, testosterone levels and oxidative stress determination were done on the 35th day of the experiment. Results: The lowest percentage of sperm parameters was related to the busulfan group and the highest was related to the carobs 1 and 2 groups. The seminal vesicles index of the carob 1 group showed a significant increase as compared to the busulfan group (p < 0. 001). A significant increase was observed in the mean value of germinal epithelium thickness, as well as thiol and catalase levels in carobs 1 and 2 groups as compared to the busulfan group (p < 0. 001). There was a significant increase in the mean level of testosterone in the carob groups as compared to the busulfan group (p < 0. 001). Also, there was a significant decrease in the mean value of malondialdehyde level in the carobs 1 and 2 groups p < 0. 001) and a significant increase in the mean value of superoxide dismutase enzyme in the carob groups as compared to the busulfan group (p < 0. 001). Conclusion: Administration of 800 mg/kg of carob extract for 35 days improved sperm quality, biochemical parameters, thickness of germinal epithelium and testosterone levels in infertile mice induced by busulfan.

Background: Scrophularia atropatana contains chemicals activating the GABA system and inhibiting glutaminergic system. As well as we know, drugs inhibiting glutamate system have analgesic effects and reduce tolerance to the analgesic effects of morphine. In the present study, effect of methanol extract of aerial parts of S. atropatana on tolerance to the analgesic effects of morphine was evaluated. Methods: The aerial parts of S. atropatana were extracted with methanol by maceration and was further analyzed to determine the content of total phenols, antioxidant activity (DPPH method) and analgesic activity. Several groups of mice received drug regimens for 4 days. Group I: Saline (10 ml/kg, i. p. ) + Saline (10 ml/kg, i. p. ), group II: Morphine (50mg/kg, i. p. ) + Saline (10mg/kg, i. p. ) and group III: Morphine (50mg/kg, i. p. ) + Extract of S. atropatana (100, 200, 400 mg/kg, i. p. )]. On the fifth day the test dose of morphine (9 mg/kg, i. p. ) in different groups were assessed. By using hot plate test, the analgesic activity of different doses of the extract was evaluated. Results: Phytochemical screening indicated the presence of total phenolics content of the extract (152 mg GAE/g) and antioxidant activity (RC50 =143µ g/ml) in DPPH method. All doses of the extract had analgesic activity. It was found that treatment with extract (100, 200 mg/kg, i. p. ) attenuated the development of tolerance to the antinociceptive effect of morphine. Conclusion: The results of the study demonstrate that S. atropatana strongly reduced tolerance to morphine and has analgesic effects. The suggested analgesic effects may be related to the phenolics content and antioxidant activity of the plant alongside inhibition of glutaminergic system.

Background: The interference of metformin with thyroid function has been recently reported in several studies. In the present research, we assessed the effect of metformin on thyroid function tests in patients with subclinical hypothyroidism associated with metabolic syndrome. Method: In a double-blind clinical trial, 60 patients were selected among who referred to outpatient endocrine clinics and met the inclusion and exclusion criteria were considered for the study. Inclusion criteria were the presence of metabolic syndrome and subclinical hypothyroidism (2. 5

Background: Osteoblasts’ activity is prerequisite for prevention from and treatment of apical periodontitis and a relatively high proportion of endodontically treated teeth will require retrograde treatment in future. Therefore, the aim of the present study was to evaluate the effect of platelet-rich plasma (PRP) on differentiation of stem cells into osteoblasts and osteoclasts. Methods: Mesenchymal stem cells were isolated from human fetal umbilical cord and cultured on two polycaprolacton/hydroxyapatite (PCL/HA) polymer scaffolds. In addition to differentiation agents, 10% PRP was added to PRP containing subgroups. After 10 days, osteoblast differentiation was assessed evaluating the osteocalcin and osterix gene levels where, in the osteoclast differentiation group the expression of tartarate-resistant acid phosphatase (TRAP) gene was evaluated. Results: Expression of TRAP gene did not reveal any significant differences between the study and control groups. There was a significant difference in osterix expression between the control and the PRP-treated groups (p < 0. 01) as well as osteocalcin gene (p < 0. 05). Conclusion: The results showed that PRP increased the osteoblastic differentiation, while it does not cause any significant increase in osteoclastic differentiation.

Background: A sensitive high-performance thin layer chromatographic (HPTLC) method was developed for simultaneous determination of beclomethasone dipropionate and salbutamol sulphate from inhalation product. Methods: Chromatographic separation was achieved on aluminium plates pre-coated with silica gel G60 F254 as the stationary phase and methanol: ethyl acetate: toluene: ammonia (3: 1: 3: 0. 15) as the mobile phase. The densitometric evaluation was carried out at 232 nm. The developed method was validated as per the ICH Q2 (R1) guidelines. Robustness of the proposed method was assessed using experimental design approach, and results were analyzed graphically. The results of sample analysis by proposed HPTLC method and reported HPLC method were statistically compared. Results: The Rf value of salbutamol sulphate and beclomethasone dipropionate was found to be 0. 38± 0. 02 and 0. 72± 0. 02, correspondingly. The response in terms of peak area was linear over the concentration range of 100-500 ng/spot and 200-1000 ng/spot for beclomethasone dipropionate and salbutamol sulphate, individually, with the regression coefficient values greater than 0. 99 for both the drugs. The limit of detection and limit of quantification for beclomethasone dipropionate were found to be 27 ng/spot and 84 ng/spot, respectively and for salbutamol sulphate were 40 ng/spot and 112 ng/spot, respectively. The proposed method was found to be statistically insignificant when compared to the reported method. Conclusion: The proposed method is robust, sensitive, accurate and precise. The method can be applied for the simultaneous estimation of beclomethasone dipropionate and salbutamol sulphate from inhalation product.

Background: Bis-phenol A (BPA) can migrate into food stuff from packaging materials and accounts for food contamination. This research was designed to measure BPA contamination in the Iranian brands of food grade oils and to find out the possible effect of production date on the amount of BPA migration. Methods: Ten well-known and top selling oils packed in various containers, were selected and sampled according to their batch number and production date stated on the label. Subsequently, BPA was extracted by reverse phase dispersive liquid-liquid extraction (RPDLLME) method and quantified by HPLC. Results: The measured quantity of BPA in the food grade oil was ranged between 0. 5 to 4. 37 µ g/g of oil samples regardless of the date of production, the Batch Number, and the producing company. Statistical analysis revealed that the difference of BPA content in oil samples did not depend on their production date. Conclusion: According to the amount of allowable migration introduced by European committee, the amount of BPA migration and consequently contamination of almost all tested samples exceeds SML. Considering the toxic effects reported especially in fetus and young children, prompt regulatory interference is needed in this area.

Background: The present study was aimed to introduce a rapid, simple and cost-effective method to detect adulterated lime juice products commercially available in the Iranian market. Methods: Twelve different brands of marketed lime juice products were randomly purchased from the local stores in Tabriz, Iran. Fresh lime juice, as a control, was prepared by squeezing lime fruits using a plain hand juicer. Ehrlich’ s reagent was used for a colorimetric analysis; solid phase extraction-thin layer chromatography (SPE-TLC) technique was utilized for fingerprinting of methanol/water fractions of samples on the silica gel plates at two wavelengths of 366 and 254 nm, before and after spraying aluminum chloride reagent; and attenuated total reflectance-infrared spectroscopy (ATR-IR) was used for further studies. Results: The obtained results from colorimetric analysis indicated appearance of orangebrown color indicating presence of limonoids in fresh lime juice and only five commercially available products. Regarding SPE-TLC fingerprinting, except for five products with identical or comparable TLC patterns to the fresh lime juice, other samples represented completely different TLC patterns, suggesting the presence of adulterants in these products. Therefore, the developed colorimetric and SPE-TLC techniques revealed some extents of adulteration in half of the studied products (58. 3%). However, in the case of ATR-IR analysis, the obtained spectra were not illustrating enough to be applied for the detection of adulterated samples. Conclusion: It can be concluded that the described colorimetric method in combination with the developed SPE-TLC technique could be utilized for the preliminary screening of adulterated lime juice products.

Background: The safety of food with animal origin means that the food consumed is considered as safe when synthetic chemical agents are absent or present at very low concentrations. The aims of the present study were to validate the Premi ® Test and four plate test (FPT) methods as well as screen and estimate the occurrence of chloramphenicol (CAP) residue in collected chicken tissues including liver, kidney and thigh muscle from Kermanshah, west of Iran. Methods: A total of 150 chicken samples were purchased from different poultry slaughterhouses in Kermanshah province, west of Iran and subjected to the FPT and Premi ® Test. Results: The Premi ® Test could not detect CAP residue at concentrations below 3 and 6 ppm in aqueous solution and kidney fluid, respectively. The highest sensitivity of FPT in the detection of CAP residue was optimally found in the agar medium inoculated with Bacillus subtilis at pH 7. 2. The Premi ® Test was more sensitive than FPT in the kidney fluid and aqueous solution. Regarding FPT results, CAP residue was found in 20% (n=30), 8. 66% (n=28) and 11. 33% (n=17) of liver, kidney and muscle samples, respectively. In the case of Premi ® Test, the most contaminated samples were liver (24%), followed by kidney (22. 66%) and muscle (19. 33%). Conclusion: It can be concluded that illegal use of CAP in Iranian poultry industries should be taken into account seriously.

Background: Sucrose is the most widely used sweetener in food and pharmaceuticals. Quantitative solubility values of this excipient in aqueous polyethylene glycol (PEG) mixtures is not abundant. Thus, the main objective of this research was to determine and correlate the equilibrium solubility of sucrose in {PEG 200 (or 400) + water} mixtures at 298. 2 K. Methods: Shaken flask method was used to determine isothermal solubility. Concentration measurements were performed by means of density determinations. Jouyban-Acree model was used to correlate both solubility sets. Results: Solubility of sucrose decreases non-linearly with the addition of either PEG200 or PEG400 to water. Jouyban-Acree model correlates solubility values with mixtures composition for both cosolvent systems. Moreover, apparent specific volume of sucrose were also calculated from density and compositions. Conclusion: Useful solubility values of sucrose at equilibrium in aqueous mixtures of PEG200 and PEG400, as well as their volumetric contributions to saturated solutions are reported.