The beneficial effects of antioxidants combination on cardiac injury induced by tetrachloromethane.

The purpose of this research was to evaluate the efficacy of carsil (CAR) either alone or in combination with α-tocopherol (α-TOCO) and/or turmeric (TUMR) against tetrachloromethane (TCM)-induced cardiomyocyte injury in rats. Administration of CAR either alone or in combination with α-TOCO and/or TUMR post-TCM injection, significantly mitigated the increases in serum troponin T, creatine kinase-MB (CK-MB) as well as interleukin-6 (IL-6), interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP). They also decline the elevation of caspase-3, vascular endothelial growth factor (VEGF) protein expression as well as DNA damage in cardiac tissues induced by TCM. The biochemical results were confirmed by histopathological investigation. Conclusion: The combination of the three antioxidants showed greater cardioprotective potential, compared to individual drugs. Therefore, this combination may be recommended as a complementary therapy to antagonize cardiac injury induced by different insults.

Isolation, characterization, and hepatoprotective properties of betulinic acid and ricinine from Tetracarpidium conophorum seeds (Euphorbiaceae).

The present study is to isolate and characterize betulinic acid and ricinine from T. conophorum seeds. Phytochemical investigation on hexane fraction of T. conophorum seeds led to the isolation of two compounds, Betulinic acid (1), and Ricinine (2). Betulinic acid and ricinine were screened against HepG2 cells and tested in vivo in CCl4 -induced experimental rats model. Results from this study showed that the compounds had hepatoprotective and cytotoxic activities. It was observed that betulinic acid inhibited HepG2 cell with percentage inhibition of 54% compared with standard doxorubicin (64%), while ricinine was inactive against HepG2 cell lines. Furthermore, molecular docking was carried out on betulinic acids and ricinine, with binding energies of -11.2 kcal/mol and -5.4 kcal/mol, respectively, indicating strong binding sites and interactions with Hepatitis B Virus DNA polymerase. Therefore, findings from this study suggest that betulinic acid possess cytotoxic and hepatoprotective properties, while ricinine exhibited hepatoprotection in CCl4 -induced liver damage. PRACTICAL APPLICATIONS: Medicinal plants contain unrestricted ability to make compounds that intrigue researchers in the quest for novel phyto-therapeutic drugs. The continuous exploration of new compounds in the medicinal plant is an auspicious strategy for the prevention of diseases. Therefore, the purpose of this research is to evaluate the cytotoxic and hepatoprotective compounds (betulinic acid and ricinine) isolated from T. conophorum seeds.

Cross Talk Between TGF-ß and JAK Expressions and Nepherotoxicity Induced by Tetrachloromethane: Role of Phytotherapy.

The aim of the current study is to assess the effectiveness of milk thistle seeds (Mth) in combination with Taraxacum officinale (Tof) and/or Camellia sinensis (Csin) against tetrachloromethane (Tcm) renotoxicity in rats. Tetrachloromethane was injected in a single dose, followed by 1-month treatments with Mth, Tof, and Csin alone or in combination. Serum urea, uric acid, and creatinine levels were significantly increased matched with the control group. Masson trichrome stain revealed increase in the deposition of fibrous tissue in the interstitium between the tubules and the renal corpuscles. Immunohistochemical analysis of kidney tissues revealed that Tcm induced an increase in the immune response of tumor growth factor ß (TGF-ß) and Janus kinase (JAK) protein expressions and cysteine-aspartic acid protease 3 (caspase 3), while B-cell lymphoma 2 (Bcl2) was downregulated. Treatment with the antioxidants in question either alone or in combination ameliorated all kidney function parameters and showed mild immune reactivity toward TGF-ß and JAK protein expressions in blood vessels and glomeruli in the kidney tissues and downregulated caspase 3 and activated Bcl2 protein expression. The combination regimen of the 3 antioxidants showed the most significant renoprotective effect. This was also confirmed histopathologically. It was concluded that the antioxidant mixture is considered as a promising candidate toward renal dysfunction and immune reactivity induced by Tcm and other toxicants.

Application of silica-supported Ir and Ir-M (M = Pt, Pd, Au) catalysts for low-temperature hydrodechlorination of tetrachloromethane.

Herein, it is presented a catalytic system for gas-phase hydrodechlorination of tetrachloromethane at low temperature and atmospheric pressure, using iridium supported on silica as parent catalyst. Iridium electronic configuration is suitable to catalyse the hydrodechlorination reactions, however, it has been rarely used in this reaction to date. The catalytic abilities were significantly improved when a second transition metal was added. Catalysts' stability and selectivity to the desired products (i.e. C1-C4 hydrocarbons) improved compared to conventional activation in hydrogen when catalysts were activated shortly with microwave irradiation. Microwave irradiation of catalysts favourably influences the homogeneity of the metallic active phase, both in terms of the size of metal crystals and the homogeneity of bimetallic systems. Addition of platinum to the 'parent' iridium catalyst improved its catalytic properties and decreased deactivation. Fresh and spent catalysts were comprehensively characterized using several techniques (BET, CO-chemisorption, XRD, XPS, electron microscopy and mass spectrometry) to determine structure-activity relationships and potential causes for catalyst deactivation. No significant changes in crystalline size or bimetallic phase composition were observed for spent catalysts (with the exception of Ir-Pd catalysts which underwent bulk carbide during the reaction).

Hepatoprotective and proapoptotic effect of Ecballium elaterium on CCl4-induced hepatotoxicity in rats.

OBJECTIVES: To investigate the effects of perorally administered juice on tetrachloromethane (CCl4)-induced hepatotoxicity model in rats. METHODS: Male Wistar rats were tube-administrated silymarin, Ecballium juice at 0.2 mL/kg and 0.7 mL/kg daily for 3 consequent days, i.e., 3.28 µg and 11.48 µg of cucurbitacin B per kg of body weight respectively. On the third day, liver damage was induced by intraperitoneal application of CCl4. On the fourth day, abdominal cavity was macroscopically examined and liver samples were taken for histopathological and immunochemical evaluation. HPLC was used to determine the content of the active substance cucurbitacin B. RESULTS: The experiment revealed that 0.7 ml/kg juice concentration expressed the highest pro-apoptotic activity, but with prevailing negative effects. Compared with the lower concentration, there was an observable vasodilatation with consequent interstitial hemorrhages and a larger scope of inflammatory damage, which suppressed the hepatoprotective effect. In the 0.2 mL/kg concentration, there was a smaller pro-apoptotic activity but other parameters had better results, and the liver parenchyma damage was reversible. CONCLUSIONS: No reactions confirming the potentially allergic effect on laboratory rats were observed; its hepatoprotective and anti-inflammatory effect was confirmed on a model of acute liver damage.

Tetrachloromethane-Degrading Bacterial Enrichment Cultures and Isolates from a Contaminated Aquifer.

The prokaryotic community of a groundwater aquifer exposed to high concentrations of tetrachloromethane (CCl4) for more than three decades was followed by terminal restriction fragment length polymorphism (T-RFLP) during pump-and-treat remediation at the contamination source. Bacterial enrichments and isolates were obtained under selective anoxic conditions, and degraded 10 mg·L(-1) CCl4, with less than 10% transient formation of chloroform. Dichloromethane and chloromethane were not detected. Several tetrachloromethane-degrading strains were isolated from these enrichments, including bacteria from the Klebsiella and Clostridium genera closely related to previously described CCl4 degrading bacteria, and strain TM1, assigned to the genus Pelosinus, for which this property was not yet described. Pelosinus sp. TM1, an oxygen-tolerant, Gram-positive bacterium with strictly anaerobic metabolism, excreted a thermostable metabolite into the culture medium that allowed extracellular CCl4 transformation. As estimated by T-RFLP, phylotypes of CCl4-degrading enrichment cultures represented less than 7%, and archaeal and Pelosinus strains less than 0.5% of the total prokaryotic groundwater community.

Forced degradation and impurity profiling: recent trends in analytical perspectives.

This review describes an epigrammatic impression of the recent trends in analytical perspectives of degradation and impurities profiling of pharmaceuticals including active pharmaceutical ingredient (API) as well as drug products during 2008-2012. These recent trends in forced degradation and impurity profiling were discussed on the head of year of publication; columns, matrix (API and dosage forms) and type of elution in chromatography (isocratic and gradient); therapeutic categories of the drug which were used for analysis. It focuses distinctly on comprehensive update of various analytical methods including hyphenated techniques for the identification and quantification of thresholds of impurities and degradants in different pharmaceutical matrices.