Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling.

In vitro antioxidant and antimutagenic activities of two polyphenols isolated from the fruits of Pistacia lentiscus was assessed. Antioxidant activity was determined by the ability of each compound to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*), to inhibit xanthine oxidase and to inhibit the lipid peroxidation induced by H(2)O(2) in K562 cell line. Antimutagenic activity was assayed with SOS chromotest using Escherichia coli PQ37 as tester strain and Comet assay using K562 cell line. 1,2,3,4,6-Pentagalloylglucose was found to be more effective to scavenge DPPH* radical and protect against lipid peroxidation. Moreover, these two compounds induced an inhibitory activity against nifuroxazide and aflatoxin B1 mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress. For this purpose, we used a cDNA-microarray containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair proteins. We found that 1,2,3,4,6-pentagalloylglucose induced a decrease in the expression of 11 transcripts related to antioxidant enzymes family (GPX1, TXN, AOE372, SHC1 and SEPW1) and DNA repair (POLD1, APEX, POLD2, MPG, PARP and XRCC5). The use of Gallic acid, induced expression of TXN, TXNRD1, AOE372, GSS (antioxidant enzymes) and LIG4, POLD2, MPG, GADD45A, PCNA, RPA2, DDIT3, HMOX2, XPA, TDG, ERCC1 and GTF2H1 (DNA repair) as well as the repression of GPX1, SEPW1, POLD1 and SHC1 gene expression.

Influence of ascorbic acid on the mutagenicity of N-methyl-N-nitrosoguanidine and nitrofurans studied by SOS chromotest.

Mutagenicity inhibition of MNNG*, NFAA* as well as of nitrovin by ascorbic acid was observed. The influence of ascorbic acid on these compounds was parallelly studied also by spectroscopy. Mutagenicity inhibition was characterized by SOS chromotest. Inhibition degree was evaluated quantitatively introducing the coefficient of inhibition. The influence of ascorbic acid was expressed most markedly in MNNG. It has been found that the decrease of mutagenicity should be mainly caused by acceleration of MNNG decomposition by ascorbic acid.

[Characteristics of the antibiotic sensitivity of nitrofuran--resistant Gram-negative bacteria of clinical origin]. / Kharakteristika antibiotikochuvstvitel'nosti nitrofuranorezistentnykh gramotritsatel'nykh bakterii klinicheskogo proiskhozhdeniia.

494 persons with various purulent inflammatory diseases were examined. Gram-negative nitrofuran resistant organisms isolated from the clinical material were found in 22.9 per cent of the cases. Representatives of Enterobacteriaceae, Klebsiella-Enterobacter-Serratia (26.8 per cent), Proteus-Providencia (16.8 per cent) and E. coli-Arizona-Citrobacter (16.1 per cent) predominated. Pseudomonas (32.1 per cent) and Acinetobacter (5.3 per cent) predominated among the aerobic gram-negative bacteria. Sensitivity of 131 strains to 10 chemotherapeutic drugs was determined. 60.4 per cent of the aerobic and 44.2 per cent of the Coli bacteria had multiple drug resistance (to 5 and more drugs). The organisms isolated from the urine and wound excretion were most resistant. Representatives of Pseudomonas and Klebsiella-Enterobacter predominated among the polyresistant cultures. High sensitivity of the isolates to gentamicin, carbenicillin and nalidixic acid was noted.

The blocking effect of disodium cromoglycate on carcinogenesis induced by benzo[a]pyrene.

Subcutaneous injection of 3 mg benzo[a]pyrene into the right hind leg of experimental rats resulted in local tumors in the area of application in all the animals. The same dose of disodium cromoglycate applied prior to benzo[a]pyrene prevented tumor formation or provoked a significant inhibition of the carcinogenic process, e.g. delay of tumor formation and of a reduced size, a number of mitoses and cytological abnormalities and a prolongation of the animal's life. In the in vitro Salmonella typhimurium mutation assay of Ames, disodium cromoglycate eliminated toxicity and mutagenicity of 5-nitro-2-furylacrylic acid. The results would suggest that the initial response of the cell to benzo[a]pyrene had been conducted through the calcium-dependent exocytic pathway, which can be efficiently blocked by disodium cromoglycate, probably by preventing the signals increase in free intracellular calcium concentration. The preserved calcium balance as a consequence of the effect of disodium cromoglycate on benzo[a]pyrene-induced cell response might be a factor responsible for the carcinogenesis inhibition phenomena. The results of the in vitro study in correlation with those obtained in vivo support the suggestion that disodium cromoglycate may influence parallel structures in various cell types.