Iranian Journal of Pharmaceutical Sciences

Background: Although the bio kinetics, metabolism and chemical toxicity of Atorvastatin are well known, until recently little attention was paid to the potential neurotoxic effect of Atorvastatin (Atv). Regarding the concrete evidences indicating Atv may reduce Coenzyme Q10 (CoQ10) levels through blockage of metalonate cycle, the present work aims to determine if Atorvastatin may provide toxic effects on brain mitochondria and whether its supplementation with two lipidicantioxidants, CoQ10 and Vit E may improve such outcomes.
Methods: to evaluate mitochondrial toxicity, male NMRI mice were first treated with Atorvastatin(bo; 20 and 60 mg/kg) every other day with or without supplementation with CoQ10 (200 mg/kg) or Vit E (40 u/kg). After a period of 4 weeks, the animals were euthanized and brain cortices were harvested ad subjected to mitochondria isolation procedure. ROS release, mitochondrial membrane potential (MMP) and cytochrome c release were performed to precisely address the probable mitochondrial injury.
Findings: Our data showed increased ROS formation, MMP collapse, mitochondrial swelling and cytochrome c release in Atorvastatin treated mice, suggesting that mitochondrial ROS formation and apoptosis signaling are likely involved in Atorvastatin neurotoxicity. Importantly according to the data from animals receiving either CoQ10 or Vit E, supplementation with these lipophilic antioxidants, remarkable reverted the corresponding Atorvastatin mitochondrial toxicity markers.
Concusion: Conclusively the present work addresses chronic Atorvastatin toxic effects on brain mitochondria and supports advantages of Vit E or CoQ10 supplementation. Whether such neurotoxic effect is correlated with CoQ10 depletion or if the improving effects of the due supplementation contribute toAtorvastatin receiving patients, needs more investigations.

Medicinal plants have attracted global attention due to their high levels of antioxidant components for prohibiting or improving various diseases including brain and memory disorders. This study was designed to investigate if the antioxidant effect of Sidr (Zizyphusspina-christi) extract can help to improve the scopolamine induced impairment of memory in Wistar rats. Animals were randomly divided into 6 groups: Control, Scopolamine at 1 mg/kg, Scopolamine+50 mg/kg Sidr extract (Zsc50+sco), Scopolamine+100 mg/kg Sidr extract (Zsc100+sco), Scopolamine+200 mg/kg Sidr extract (Zsc200+sco) and Scopolamine+diazepam at 1 mg/kgbw (D+sco). Antioxidant activity and total phenolic content of Z. spina-christi as well as the Passive avoidance test, antioxidant capacity and MDA level of plasma and brain were evaluated.Scopolamine increased the recorded initial latencies but decrease the step-through latency in comparison with those of control group. The use of Sidr at 50, 100 and 200 mg/kg attenuate these abnormalities and the impaired passive avoidance memory was improved. Although scopolamine didn’t cause any change in the antioxidant capacity plasma and brain, it increased the MDA level of plasma and brain tissues. Also use of Sidr increased the antioxidant capacity and decreased the MDA level of plasma and brain tissues.The results suggest that Z. SC might act to attenuate scopolamine induced brain and memory impairments due to its high antioxidant contents. The separation of the specific compound responsible for observed antioxidant activity with protective effect against brain and memory disorders still need further researches.

Radiotherapy, a highly effective way to destroy breast cancer, causes skin adverse effects. A considerable amount of studies have been conducted to find a way to alleviate or relieve dermal adverse effects of radiation. The aim of this study was to observe the clinical effect of Elaeagnus angustifolia L. cream to treat radiotherapy-induced skin destruction in breast cancer patients.Thirty two patients suffering from different stages of radiotherapy-induced skin reactions were evaluated in a double-blind randomized study; 16 patients in the treatment group received Elaeagnus angustifolia cream, while the other 16 patients, served as control group.Two weeks after the treatment, patients in Elaeagnus angustifolia group showed significantly lower skin reaction grade compared with placebo group. The attitude of the patients of Elaeagnus angustifolia group about dryness, itching, pain, burning, blisters and sores was significantly improved after two weeks of treatment.Elaeagnus angustifolia cream may effectively reduce the radiotherapy-induced dermal injury.

The green synthesis of 5-(4-aminophenyl)-4-aryl-4H-1,2,4-triazole-3-thiol was achieved in four steps. In the first step, 4-amino benzoic acid was refluxed in ethanol along with catalyst Conc. Sulphuric acid to produce ethyl-4-amino benzoate I. Further compound I was refluxed with hydrazine hydrate in ethanol to produce 4-amino benzohydrazide II. Compound II was refluxed in ethanolic potassium hydroxide with carbon disulfide to produce 5-(4-aminophenyl)-1, 3, 4-oxadiazole-2-thiol III. Compound III refluxed in ethanol with different substituted primary aryl amine gave title compounds 5-(4-aminophenyl)-4-aryl-4H-1, 2, 4-triazole-3-thiol IVa-o. The compounds obtained were identified by FT-IR, 1H-NMR, GC- mass spectroscopy data, and elemental analysis and also screened for in-vivo antimicrobial activity. In vitro antibacterial activity was carried out against organisms like E.coli. K.pneumonia, S.aureus, and B.subtilis as well as in vitro antifungal activity were carried out against organisms like A.niger and S.cerevisiae. In vitro antimicrobial evaluation, the most potent broad spectrum compound IVc, IVd, and IVf were found significant agent against standard drug Norfloxacin and Ketoconazole.

In this study, we compared the effects of Calendula and Alpha ointment in the treatment of burn wounds and also compared its results with silver sulfadiazine (SSD). Seventy-five male Sprague-Dawley rats were divided into five groups, and similar burn ulcers were produced on anterior surface of thigh of rats. In the first group of rats no treatment was applied, base gel was applied topically to group II, in groups III-V, Alpha, SSD, and Calendula preparations were applied, respectively. Wound healing, contraction, and histopathological evaluation were evaluated at the end of 7, 14, and 21 days. Alpha ointment was equally effective as Calendula gel, and had better efficacy compared to SSD for all markers of wound healing at days of 7, 14, and 21.Alpha and Calendula preparations are less expensive drugs and significantly improve the quality of wound healing and scar formation and are more appropriate treatment choices than SSD. Therefore, we recommended them as alternative to SSD, especially in patients with low economical backgrounds or in those who show adverse reactions to SSD.

Nepeta glomerulosa Boiss. is a medicinal plant used in traditional medicine. The aim of this study was to evaluate the anti-melanogenesis inhibitory activity of Methanol (MeOH), n-hexane, acetate (EtAc), dichloromethane (CH2Cl2), n-butanol (BuOH), and H2O extracts isolated from N. glomerulosa in B16 melanoma cell line. The B16F10 cell line viability after treatment with increasing concentrations of different extracts of the plant (50-200 μg/ml) was measured by using MTT. The inhibitory effect on synthesis of melanin, mushroom tyrosinase activity, cellular tyrosinase, and effect on oxidative stress was determined by the colorimetric and fluorometric method. The data showed that at concentrations <200 μg/ml, all extracts did not show significant toxicity on melanoma cells. The amount of melanin synthesis by MeOH and CH2Cl2 extracts and mushroom tyrosinase activity by the MeOH extract declined in B16F10 cells. In addition to the capacity of MeOH, n-hexane and CH2Cl2 extracts in decreasing the amount of reactive oxygen species (ROS) in melanoma cells all extracts revealed the remarkable antioxidant activity. Our results showed the melanogenesis inhibitory and antioxidant effects of N. glomerulosa on B16F10 cells may recommend a novel agent in diminishing skin pigmentation and skin aging in cosmetic industry.

Type 1 diabetes is a chronic disease characterized by the body's inability to produce insulin due to destruction of the beta cells. There is increasing evidence that reactive oxygen species (ROS) play a major role in the development of diabetic complications. The purpose of this study is to investigate the effects of troxerutin administration on oxidative stress markers in blood of STZ-induced diabetic rats. Male Wistar rats were divided into 4 groups as: control (con), control-troxerutin (CON-TRX), diabetes (Dia), diabetic-troxerutin (DIA-TRX). Type 1 diabetes was induced by injection of streptozotocin (STZ) (i.p, 55mg/kg) and lasted for 10 weeks. Animals received oral administration of troxerutin (150 mg/kg) for 4 weeks. At the end of study, malondialdehyde (MDA, the main product of lipid peroxidation), activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were measured spectrophotometrically. Induction of diabetes with STZ resulted in increased MDA levels and decreased blood antioxidant capacity as compared with those of controls (P<0.05). Pre-treatment of diabetic rats with troxerutin significantly decreased the levels of MDA (P<0.01) and increased the activity of antioxidant enzymes SOD, GPX, and CAT compared to untreated-diabetic groups. Troxerutin had no significant influence on non-diabetic rats. These findings showed that troxerutin may prevent oxidative complications of diabetic circumstances by elevating antioxidant enzymes activities and reducing lipid peroxidation.

In vitro studies on cancer cell lines still constitute a major part of cancer research. It is very important that the researchers consider the importance of basic conditions of working with different cell lines. To the best of authors’ knowledge, this study is the first one to report the effect of seeding density on the growth curve of three human cancer cell lines. These cell lines include human breast adenocarcinoma MCF-7 cell line, human ovary carcinoma A2780 cell line and human melanoma A375 cell line. The cell lines were seeded at 4 different seeding densities: 4000, 5000, 15000 and 50000 cells/cm2 of culture surface. Following seeding the cells and on daily basis, cell count was done with trypan blue assay. The experiment was done in triplicate. The growth curves of the cells were constructed using Microsoft Excel and population doubling time (PDT), lag time (LT) and saturation density (SD) were calculated. The results showed that the seeding density affects the general pattern of the growth curve. At lower seeding densities, the growth curves have a more expected pattern rather than in higher seeding densities. Also, seeding density does not affect the LT, while it has some effects on SD and PDT.