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The cellulase activity of Bacillus subtilis AS3 was enhanced by optimizing the medium composition by statistical methods. The enzyme activity with unoptimised medium with carboxymethylcellulose (CMC) was 0.07 U/mL and that was significantly enhanced by CMC, peptone, and yeast extract using Placket-Burman design. The combined effects of these nutrients on cellulase activity were studied using 22 full factorial central composite design. The optimal levels of medium components determined were CMC (1.8%), peptone (0.8%), and yeast extract (0.479%). The maximum enzyme activity predicted by the model was 0.49 U/mL which was in good agreement with the experimental value 0.43 U/mL showing 6-fold increase as compared to unoptimised medium. The enzyme showed multisubstrate specificity, showing significantly higher activity with lichenan and β-glucan and lower activity with laminarin, hydroxyethylcellulose, and steam exploded bagasse. The optimised medium with lichenan or β-glucan showed 2.5- or 2.8-fold higher activity, respectively, at same concentration as of CMC.

1,1-Dichloroethylene (DCE) exposure evokes lung toxicity with selective damage to bronchiolar Clara cells. Recent in vitro studies have implicated CYP2E1 and CYP2F2 in the bioactivation of DCE to 2-S-glutathionyl acetate [C], a putative conjugate of DCE epoxide with glutathione. An objective of this study was to test the hypothesis that bioactivation of DCE is catalyzed by both CYP2E1 and CYP2F2 in murine lung. Western blot analysis of lung microsomal proteins from DCE-treated CD-1 mice showed time-dependent loss of immunodetectable CYP2F2 and CYP2E1 protein. Dose-dependent formation of conjugate [C] was observed in the lungs of CD-1 mice treated with DCE (75-225 mg/kg), but it was not detected after pretreatment with 5-phenyl-1-pentyne (5-PIP). Treatment of mice with 5-PIP and also with diallyl sulfone (DASO 2 ) significantly inhibited hydroxylation of p-nitrophenol (PNP) and chlorzoxazone (CHZX). Incubation of recombinant CYP2F3 (a surrogate for CYP2F2) and recombinant CYP2E1 with PNP and CHZX confirmed that they are substrates for both of the recombinant enzymes. Incubation of the recombinant enzymes with DASO 2 or 5-PIP significantly inhibited hydroxylation of both PNP and CHZX. Bronchiolar injury was elicited in CD-1 mice treated with DCE (75 mg/kg), but it was abrogated with 5-PIP pretreatment. Bronchiolar toxicity also was manifested in the lungs of CYP2E1-null and wild-type mice treated with DCE (75 mg/kg), but protection ensued after pretreatment with 5-PIP or DASO 2 . These results showed that bioactivation of DCE in murine lung occurred via the catalytic activities of both CYP2E1 and CYP2F2 and that bioactivation by these enzymes mediated the lung toxicity.

No abstract

The indiscriminate use of carbofuran to improve crop productivity causes adverse effects in nontargets including mammalian systems. The objective of this study was to evaluate carbofuran induced oxidative stress in rat brain stem and its attenuation by curcumin, a herbal product. Out of 6 groups of rats, 2 groups received two different doses of carbofuran, that is, 15 and 30% of LD50, respectively, for 30 days. Out of these, 2 groups receiving same doses of carbofuran were pretreated with curcumin (100 mg/kg body weight). The levels of antioxidants, TBARS, GSH, SOD, catalase, and GST were determined in rat brain stem. The 2 remaining groups served as placebo and curcumin treated, respectively. The data suggested that carbofuran at different doses caused significant alterations in the levels of TBARS and GSH in dose dependent manner. The TBARS and GSH contents were elevated. The activities of SOD, catalase, and GST were significantly inhibited at both doses of carbofuran. The ratio of P/A was also found to be sharply increased. The pretreatment of curcumin exhibited significant protection from carbofuran induced toxicity. The results suggested that carbofuran at sublethal doses was able to induce oxidative stress in rat brain which could be attenuated by curcumin.

Aim: Phytocompounds are important due to their uniqueness, however, only few reach the development phase due to their poor pharmacokinetics. Therefore, preassessing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties is essential in drug discovery. Methodology: Biologically diverse databases (Phytochemica, SerpentinaDB, SANCDB and NuBBEDB) covering the region of India, Brazil and South Africa were considered to predict the ADMET using chemoinformatic tools (Qikprop, pkCSM and DataWarrior). Results: Screening through each of pharmacokinetic criteria resulted in identification of 24 compounds that adhere to all the ADMET properties. Furthermore, assessment revealed that five have potent anticancer biological activity against cancer cell lines. Conclusion: We have established an open-access database (ADMET-BIS) to enable identification of promising molecules that follow ADMET properties and can be considered for drug development.

The present study reports the antioxidant, cytotoxic and anti-leishmanial activities of cinnamaldehyde and eugenol. Both the compounds are naturally present in cinnamon and bay leaf. Eugenol is abundantly present in clove. The antioxidant potential was measured in terms of reducing power (FRAP assay), nitric oxide (NO) radical scavenging ability and anti-lipid peroxidative activities. MTT assay was used to evaluate the effect of test compounds on cell viability of prostate cancer cell line (PC-3) as well as for the assessment of in vitro growth inhibition of promastigotes as a measure of anti-leishmanial activity.  Eugenol exhibited considerable NO radical scavenging (63%) and reducing abilities (FRAP value 127×104 µM/mM) while cinnamaldehyde showed comparatively better protective efficacy against lipid peroxidation in rat brain and kidney homogenates (up to 40%). Cinnamaldehyde also displayed substantial cytotoxic activity (75%) against PC-3 cell line. Both the compounds exhibited moderate anti-leishmanial activity and IC50 values for eugenol and cinnamaldehyde were found to be 0.681 g/ml and 1.426g/ml, respectively. The study revealed that both the test compounds have noticeable antioxidant and cytotoxic activities.

Cellulose degrading Bacillus spp. (AS1, AS2, and AS3) were isolated from cow dung and identified phylogenetically by 16S ribosomal RNA (16S rRNA) sequence analysis. Bacillus sp. AS1 showed 99% homology with Bacillus megaterium whereas, Bacillus sp. AS2 and AS3 were similar to B. subtilis. The activity of extracellular carboxymethyl cellulase in presence of 1% carboxymethyl cellulose at 508C was 0.04 U/mL for Bacillus sp. AS1 and 0.06 U/mL for Bacillus sp. AS2 at pH 7.0, whereas higher activity of 0.08 U/mL was observed for Bacillus sp. AS3 at pH 9.0. Crude cellulase from all the three Bacillus sp. were stable over a wide range of pH (5.0-9.0) and thermally stable up to 608C. Carboxymethyl cellulase, filter paperase, and b-glucosidase activity of Bacillus sp. AS3 was 0.07, 0.02, and 0.04 U/ml, respectively. Degradation of leaf litter biomass treated by Bacillus sp. AS3 showed 47% drop in carbon:nitrogen (C:N) ratio and x-ray diffractograph revealed decline in crystalline structure.