Cytotoxicity and genotoxicity of butyl cyclohexyl phthalate.

Butyl cyclohexyl phthalate (BCP) is frequently used in personal care products, medical and household applications. The aim of this study is therefore to evaluate possible cytotoxicity and genotoxicity of BCP using in vitro and in vivo assays. The in vitro cytotoxic effect of BCP was investigated on mouse fibroblastic cell line (L929 cells) by MTT assay. The result showed that BCP inhibits cell proliferation in a concentration-dependent manner (IC50 value = 0.29 µg/mL). For genotoxicity assessment, tested concentrations of BCP demonstrated mutagenic activity in the presence of S9 mix with the Salmonella strain TA100 in the Ames test. Results showed that BCP is a secondary mutagenic substance even in low concentrations. The data obtained from 28-days repeated toxicity tests on mice revealed that BCP caused abnormalities of chromosome number, in a dose-dependent manner. Additionally, DNA damage, particularly DNA strand breaks, was assessed by Comet assay. The test result shows that BCP seemed to have genotoxic potential at a high level of exposure.

Antimicrobial and antioxidant activities with acute toxicity, cytotoxicity and mutagenicity of Cystoseira compressa (Esper) Gerloff & Nizamuddin from the coast of Urla (Izmir, Turkey).

The aim of the study was to evaluate the biological activities with toxic properties of the methanol, hexane, and chloroform extracts of Cystoseira compressa (Esper) Gerloff & Nizamuddin from the Coast of Urla in the Aegean Sea. The extracts of C. compressa were tested for their antimicrobial and antioxidant activities in this study. Cytotoxic and mutagenic potentials of the extracts were also evaluated using cell culture and mutagenicity assays. Hexane extract was found to have higher total flavonoid and phenolic contents than the other extracts and exerted higher antioxidant activity than other extracts. All extracts exhibited moderate antimicrobial activity against tested microorganisms (minimum inhibitory concentration ranges are 32-256 µg/mL). The results indicated that the extracts had no significant cytotoxic activity against human hepatocellular carcinoma Hep 3B cell line in all treated concentrations (5-50 µg/mL) and did not show mutagenicity in the Ames test. Lethality was not observed among mice treated with oral doses of the extracts. In conclusion, results of investigations indicate that brown alga C. compressa is a natural source of antioxidant. It has moderate antimicrobial activities with no toxicity.

Induction of oxidative stress and histological changes in liver by subacute doses of butyl cyclohexyl phthalate.

Phthalates are esters of phthalic acid and are mainly used as plasticizers in a wide variety of products and applications. There is no information on butyl cyclohexyl phthalate (BCP) toxicity. This study was performed to evaluate the histopathological effects and to determine oxidative stress inducing potential in liver by subacute exposure of BCP. The animals of the treatment groups were orally administered 100, 200, and 400 mg/kg/day BCP for 5 consecutive days per week during 28 days. As a result, no significant changes were observed in body weight gains, and absolute and relative liver weights of liver of BCP treated mice, when compared with control group. Although the degree of lipid peroxidation in the liver tissue of all BCP exposure groups were significantly higher than those of the control (p < 0.01), SOD and CAT activities in liver tissue of mice of 200 and 400 mg/kg exposure groups were significantly lower than those of the controls (p < 0.01). Moreover, BCP caused dose-dependent histological changes in the liver of mice such as congestions in vena centralis, an enlargement of the sinusoids, degeneration in hepatocytes, vacuole formations and presence of lipid droplets in hepatocytes, eosinophilic cytoplasm. While iNOS immunoreactivity was increased in all treatment groups, Type IV collagen and Connexin 43 immunoreactivities were decreased in all treatment groups compared with the control group. Significant decrease was observed in the number of TUNEL-positive liver cells of BCP treated mice. These results suggested that BCP exposure induces oxidative stress in liver and exposure of BCP during long time period could lead to hepatocarcinogenesis.

Viper venom induced inflammation with Montivipera xanthina (Gray, 1849) and the anti-snake venom activities of Artemisia absinthium L. in rat.

The present study was conducted to explore the characterization of Montivipera xanthina crude venom partially by in vitro and in vivo and the anti-snake venom activities of Artemisia absinthium L. in comparison with carrageenan-induced acute inflammation model in rats. The LD50 value was estimated as 8.78 mg/kg within 24 h by different venom doses administrated intraperitoneally in mice. The IC50 value was 0.43 ± 0.18 µg/ml after 48 h treatment while the calculated value was 0.73 ± 0.10 µg/ml for the culture media totally refreshed after 2 h treatment with venom. Wistar rats were treated intraperitoneally with A. absinthium extract, 30 min before venom or carrageenan was injected subplantarly into the left hind paw. Intraperitoneal administration of 25 and 50 mg/kg extract was inhibited venom induced paw swelling at 0.5, 1, 2 and 3 h (p < 0.05) while 12.5, 25 and 50 mg/kg extract treatment was inhibited carrageenan-induced paw swelling at 2, 3, 4 and 5 h (p < 0.05). In conclusion, the in vivo toxicity and inflammatory actions and in vitro cytotoxic actions of crude M. xanthina venom were performed as a first report and inhibition of venom-induced inflammation by methanolic extract of A. absinthium was described.

The novel oral imatinib microemulsions: physical properties, cytotoxicity activities and improved Caco-2 cell permeability.

The objective of this study was to formulate imatinib (IM) loaded to water-in-oil (w/o) microemulsions as an alternative formulation for cancer therapy and to evaluate the cytotoxic effect of microemulsions Caco-2 and MCF-7. Moreover, permeability studies were also performed with Caco-2 cells. W/o microemulsion systems were developed by using pseudo-ternary phase diagram. According to cytotoxicity studies, all formulations did not exert a cytotoxic effect on Caco-2 cells. Furthermore, all formulations had a significant cytotoxic effect on MCF-7 cells and the cytotoxic effect of M3IM was significantly more than that of other microemulsions and IM solution (p < 0.05). The permeability studies of IM across Caco-2 cells showed that permeability value from apical to basolateral was higher than permeability value of other formulations. In conclusion, the microemulsion formulations as a drug carrier, especially M3IM formulation, may be used as an effective alternative breast cancer therapy for oral delivery of IM.

Antioxidant, anti-inflammatory activities and acute toxicity of the polyherbal formulation: Romix®.

CONTEXT: Polyherbal formulations containing different plants are used for the treatment of various diseases. Romix® powder is a polyherbal formulation consisting of 14 traditionally used herbs and is used as a food supplement. There is no information about pharmaceutical activities of Romix®. OBJECTIVE: This study determined the total phenolic and total flavonoid content, and investigated the antioxidant and anti-inflammatory activities and acute toxicity of Romix®. MATERIAL AND METHODS: The total phenolics in the extracts were determined colorimetrically by using the Folin-Ciocalteu reagent. The total flavonoid content of the extracts was evaluated by a spectrophotometric method. The quercetin content of the extract was analyzed using the high-performance liquid chromatography (HPLC) method. Antioxidant activity of the extracts was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assays. The anti-inflammatory activity was evaluated by the carrageenan-induced paw edema test in the rat. RESULTS: The flavonoid and phenolics contents of Romix® were 50.58 and 265.83 mg/g in ethanol extract and 18.60 and 222.50 mg/g in water extract, respectively. Total quercetin content of Romix® was determined as 2.857 mg/g. Antioxidant activity results showed that ethanol extract in 1 mg/mL concentration (4.49775 µg/mL) had moderate antioxidant activity than water extract in the same concentration (4.28191 µg/mL). Intraperitoneal administration of 25 mg/kg Romix® extract exhibited anti-inflammatory activity and inhibited paw swelling at 1, 2, 3, 4, 5 and 6 h in rats with no acute toxicity. CONCLUSION: These findings suggest that Romix® due to its antioxidant and anti-inflammatory activities may be useful in the prevention or treatment of aging-related and inflammatory diseases.

Comparison of cefpodoxime proxetil release and antimicrobial activity from tablet formulations: complexation with hydroxypropyl-ß-cyclodextrin in the presence of water soluble polymer.

This study aims to prove the complexation of cefpodoxime proxetil (CP) by hydroxypropyl-ß-cyclodextrin (HP-ß-CD) in the presence of sodium carboxymethyl cellulose (Na CMC), and makes a comparison of commercial tablets by dissolution and antimicrobial activity studies. The CP--HP-ß-CD complex was prepared by kneading method and characterized by SEM, FTIR and DSC. The solubility method was used to investigate the effect of HP-ß-CD and Na CMC on the solubility of CP. The complex tablets were prepared using direct compression method. Dissolution studies were performed with complex tablets and commercial tablets in pH 1.2, 4.5, 6.8 and 7.4 buffer solutions. It was observed that complexation occurred in all formulations, and HP-ß-CD is able to increase CP solubility and dissolution rate of CP was improved from complex tablets, when compared with commercial tablets. Furthermore, the antimicrobial activity studies revealed that the CP--HP-ß-CD complex and complex tablets were shown to have more effective antimicrobial activity than commercial tablets. It is evident from the results that complexation with HP-ß-CD in the presence of Na CMC is feasible way to prepare a more efficient tablet formulation with improved dissolution and antimicrobial activity.