Iranian Journal of Pharmaceutical Sciences

Probucol (PB) is a drug commonly used for the treatment of hyperlipidemia and atherosclerosis. In our previous study, we have proved that PB can ameliorate abdominal aortic aneurysm (AAA) induced by elastase in mice through its anti-inflammatory and anti-oxidative effect. In this study, the water solubility and oral absorption of PB were improved by encapsulating PB into nanostructured lipid carriers (PB-NLC), and the effects of NLC on the anti-AAA effects of PB were evaluated and compared to the PB free drug. AAA mouse model was constructed by incubating the mouse aorta with elastase. Mice in the drug-treated groups were given PB free drug or PB-NLC at a PB dose of either 10 mg/kg or 20 mg/kg daily, and mice in the model group were treated with saline. The arterial wall and the degradation grade of the elastic lamina were investigated by HE staining and aldehyde fuchsine staining of the aortic sections. Infiltration of macrophages and degree of inflammation were evaluated by immunohistochemical staining of CD68 and TNFα, respectively, in the aortic sections. In addition, the absorption improvement of PB by the NLC nano-formulation was evaluated through determining and comparing the steady-state plasma concentration of PB in the PB free drug or PB-NLC treated mice group. When treating the mice with AAA with an equal dose of PB, PB-NLC more significantly inhibited expansion of the abdominal aortas and maintained the integrity of the aortic walls, compared with the PB free drug. The NLC nano-formulation significantly increased the steady-state plasma concentration of PB. PB-NLC significantly increased the absorption and protective effects of PB against elastase-induced AAA in mice.

Arsenic is a highly toxic element that is widely distributed in environment. Antioxidants depletion and oxidative stress is now considered as one of the possible mechanisms of arsenic-induced toxicity. Nacetylcysteine (NAC) and Curcumin (Cur) are potential antioxidants that can compensate the depletion of antioxidants. This study aimed to compare the hepatoprotective effect of Cur and NAC and their influences on total antioxidant capacity (TAC) in rats exposed to arsenic.The Rats were randomly divided into 6 groups, including control, G2 (arsenic), G3 (arsenic + NAC), G4 (arsenic + Cur), G5 (arsenic + NAC, post treatment) and G6 (arsenic + Cur, post treatment). Rats were exposed to 20mg/kg arsenic (by gavage) for 30 days and then treated with 300mg/kg NAC (by gavage) and 100mg/kg Cur (by gavage), individually. Serum level of TAC was measured using specific ELISA kits. Liver samples were collected for histopathological and morphological examinations. Arsenic treatment induced severe lesions and hepatocytes damages. Not only arsenic reduced significantly (p<0.001) the number of hepatocyte cells (27.83±1.47), but also it declined significantly (p<0.001) the mean of TAC value (0.4±0.1 μmol/l) in rats received arsenic alone. Treatment with NAC and Cur increased the mean of TAC value, enhanced the number of hepatocytes and reduced morphological damages of liver cells.NAC and Cur play important hepatoprotective roles against arsenic-induced toxicities by compensating cellular antioxidants. Therefore, NAC and Cur therapy can mitigate arsenic-induced toxicity, due to their anti-oxidative
stress properties.

Detection and management of cancer-related symptoms is a key component in children‟s quality of life. We evaluate symptoms and their severity in Iranian pediatric oncology outpatients using Therapy-Related Symptom Checklist for Children (TRSC-C). This was a cross-sectional study conducted in two outpatient pediatric oncology settings. We included all patients aged between 5-17 years. The validated and reliable Persian translated version of TRSC-C was used to study the symptoms. Overall 1425 symptoms were documented from 162 patients (mean age 8.6 ±3.2, acute lymphoblastic leukemia: 76.5%). In 96.3% of patients at least one symptom was present. Twenty (12.34%) patients experienced at least 15 events. Irritable, loss of appetite, cough, pain and hair loss were the top 5 frequent symptoms. The highest mean severity scores were also belonged to irritable, loss of appetite, and hair loss. We found no significant difference between gender, age group or time of the last chemotherapy with mean total severity scores or total number of symptoms (P>0.05). In conclusion, TRSC-C is an appropriate symptom assessment checklist for our settings and it would give us the ability to track symptoms and designate clinical interventions based on the frequent and severe identified symptoms.

Ficus carica is a worldwide important crop. Its different parts such as leaves, stem barks, fruit and roots are used in traditional medicine from ancient age to treat the various diseases. In this research, total phenolic content, antioxidant activity, yield of extract and profiling of phenolic compounds of maturated leaves of different cultivars of F. carica were investigated by using two different extraction processes: ultrasound-assisted extraction (UAE) and maceration. The total phenolic content (TPC) was calculated by using Folin-Ciocalteu assay, while DPPH and ABTS assays were used for analysed the antioxidant capacity. Additionally, liquid chromatography (LC) coupled to mass spectrometry (MS) was used to study the individual phenolic compounds present in leaves. Using DPPH assay, the percentages of inhibition and Trolox equivalent antioxidant capacity were found to vary from 66.19 ± 1.01 to 87.06 ± 0.93 % and 53.67 ± 0.81 to 70.25 ± 0.74 mg TE/g DL, respectively, for extracts obtained by maceration. In the case of ultrasonication extraction, these values ranged from 72.84 ± 1.26 to 92.04 ± 1.24 % and 60.73 ± 0.92 to 74.19 ± 0.99 mg TE/g dry leaves (DL). While ABTS assay the latter parameters were found to vary from 96.61 ± 0.22 to 99.33 ± 0.23 % and 56.81 ± 0.12 to 58.32 ± 0.13 mg TE/g DL for maceration, as well as from 97.82 ± 0.23 to 99.79 ± 0.13 % and 57.48 ± 0.13 to 58.57 ± 0.07 mg TE/g DL for ultrasonication extraction. The total phenolic contents varied between 10.70 ± 0.20 to 21.18 ± 0.68 mg GAE/g DL, and 12.94 ± 0.23 to 23.04 ± 0.30 mg GAE/g DL, respectively for the latter extraction processes. The percentages of yields varied from 7.20 ± 0.20% to 13.05 ± 0.23% and 8.25 ± 0.25% to 15.20 ± 0.20 %, respectively, for maceration and ultrasonication extraction. In conclusion, extracts from leaves of F. carica obtained by UAE process showed the highest antioxidant activity, phenolic contents and extraction yields as compared to maceration process. In comparison amongst the leaves, the ‘Violette solise’ cultivar showed the highest antioxidant activity and contain highest phenolic contents. Finally, the extract of this cultivar contained phenolic acids (dihydroxybenzoic acid di-pentoside, caffeic acid, caffeoylmalic acid, coumaroylmalic acid, ferulic
acid malate, and psoralic acid glucoside), C-glycosides flavones, rutin and prenylgenistein.

This article was aimed to analyze the essential oils from Cinnamomum camphora leaves of four areas by GC-MS and to study their analgesic properties. Analgesia test was performed employing mouse acetic acid writhing method, hot plate method and reserpine induced migraine model, and plasma and brain tissue NO and prostaglandin E2 (PGE2) contents were determined. The major compounds from essential oils of Suzhou C. camphora leaves (SZ), Nanjing C. camphora leaves (NJ), Nantong C. camphora leaves (NT) and Lianyungang C. camphora leaves (LY) are different, but they all consist of nerolidol and (E)-α-atlantone. (E)-α-atlantone exists as the main constituent and it is first reported in this plant. In the hot plate test, NJ or LY (1 ml×kg-1 each) significantly prolonged the reaction time after 30 min treatment and plasma and brain tissue NO and PGE2 in the mice with NJ or LY (1 ml·kg-1) administration were significantly decreased. In the acetic acid-induced writhing test, NJ (1 ml×kg-1 each) significantly decreased the number of acetic acid-induced writhes in mice compared to the animals that received vehicle only. In the migraine test, Plasma NO in the mice with NJ or NT (1 ml×kg-1) and NJ (0.25 ml×kg-1) administration were significantly decreased. NJ and LY have obvious analgesic effect and the mechanism is related to the reduction of central and peripheral NO and PGE2 levels. NJ was effective on migraine mice induced by reserpine and the mechanism may be related to the inductionof NO release. NJ and LY have significantly analgesic effects in three experimental models of pain.

Elephantopus scaber Linn. was used traditionally for treating various diseases. Previous studies found the cytotoxicity of this herb against differentcell lines. This study aimed to determine the effectiveness of the ethanolic extract of E.scaberin inducing apoptosis by observing itseffect on caspase cascade.This ethanolic extract was obtained by maceration method using 96% ethanol. It was fractionated with petroleum ether to discard compounds with very low polarity.This step wasfollowed bythe fractionation with chloroform to isolate compounds with optimum polarity. The soluble part in chloroform was dried and used for the assay. The immunocytochemistry method used specific antibodies for caspase-8, caspase-3, and caspase-9 to observe the expressions of each caspase. T47D cell line was treated with the chloroform fraction of E. scaber with the concentrations of 7.06 μg/ml and 3.53μg/ml. The results of the immunocytochemistry showed that this chloroform fraction increased the expressions of caspase-8, caspase-3, and caspase-9 proteinssignificantly.Such increase led to apoptotic cells.This finding supported the development of E.scaber extract as ananticancer agent.

Acetaminophen is the most commonly used analgesic and fever-lowering agent that is prescribed in a high percentage of patients. Due to the high prevalence of the administration of this drug, even a small percentage of errors in prescription can be significant and have important implications. The aim of the present study was to determine the frequency of supratherapeutic dosing of acetaminophen among hospitalized adult patients and its association with clinical outcomes. We conducted a retrospective, cross sectional study of all hospitalized adult patients in a teaching hospital affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. During the three-month study period, 4,781 (24.83%) out of 19,252 hospitalized cases received acetaminophen. Of those who received acetaminophen, 264 (5.5%) cases received a supratherapeutic dose at least once. Of 611 incidences of supratherapeutic dosing, 99.1% occurred in surgical wards and surgical intensive care units (ICUs), and 98.8% was associated with receiving parenteral formulations of acetaminophen. Multivariate analysis indicated supratherapeutic dosing of acetaminophen was significantly associated with multiple factors including female gender, older age, and longer length of hospital stays. All things considered, the percentage of hospitalized adult patients who received any dose of acetaminophen at our center was considerably less than other countries. Despite this, the frequency of instances of supratherapeutic dosing of this medication was significant (i.e. 17.6 days per 1,000 patient-days). Considering recent reports concerning the risk of hepatotoxicity associated with the repeated use of supratherapeutic doses of acetaminophen, continuous monitoring of acetaminophen utilization in order to prevent these instances is needed. Furthermore, based on the low percentage of patients who receive acetaminophen at our center, conducting research to study the pattern of prescription of analgesics and antipyretics in our center and its association with clinical outcome is logical.

Garcinia atroviridis (Clusiaceae) has been used as a postpartum medication agent in folkloric medicine. However, its biological potential has not been fully evaluated. The present study was aimed to evaluate the
antioxidant efficacies, cholinesterase enzyme inhibitory and antimicrobial activity of the stem bark extracts of G.atroviridis. Successive extraction was done using solvents of varied polarity. The antimicrobial activity was performed using the disc diffusion method by determining the inhibition zone and further evaluated for their minimum inhibition concentration (MIC) and minimum lethal concentration (MLC). Anti-cholinesterase activity was determined by spectrophotometric method while antioxidant activity was evaluated by DPPH radical scavenging. The extracts showed significant inhibitory activity against food borne bacteria. However, only dichloromethane extract exhibited the anti-yeast potential against Candida utilis and none of the extracts tested showed anti-fungi activity. For cholinesterase enzyme inhibitory activity, ethyl acetate extract exhibited the strongest acetylcholinesterase (AChE) inhibitory activity with an IC50 value of 5.46 ± 2.91 μg/mL while water extract showed the lowest IC50 value (29.31 μg/mL) against butyrlcholinesterase (BChE). For antioxidant activity, methanol extract showed moderate activity against DPPH radicals with EC50 value of 71.96 μg/mL.The dichloromethane extract exhibited significant antimicrobial activity while ethyl acetate showed the strongest acetylcholinesterase (AChE) inhibitory activity. The present study showed the significance of this commercial plant as the potential source of bioactive compounds.