22^nd World Congress on Toxicology and Pharmacology July 14-15, 2020 Kyoto, Japan

Dr. Yousefipour received her PhD in Environmental Toxicology from Texas Southern University (TSU) in 2003. At the present time, she is a tenure full professor at TSU. Yousefipour has been studying the effect of environemtnal pollutants on cardiovascular system and has authored or co-authored more than 25 scientific papers in prominent journals. Yousefipour has been the recipient of Caroline Tum Sudan Professional Opportunity Award from American Physiological Society as well as several awards from TSU Research Week program. She is a member of several professional organizations including American Heart Association, American Physiological Society, and Society of Toxicology.

Nitric oxide (NO), an endogenous vasodilator, is a key regulator of basal vascular tone. Peroxisome proliferator activated receptor  (PPAR) ligand, clofibrate, has been reported to increase production of NO. Protein kinases C (PKC), a family of protein kinase enzymes, is involved in controlling the function of proteins through phosphorylation of hydroxyl groups of serine and threonine amino acid residues. Protein kinases A (PKA) is a cAMP-dependent protein kinase. There are evidence in support of clofibrate effect on NO production/availability independent of NO synthesis. Production of NO has been linked to protein kinases PKA and C-mediated signaling mechanisms. Therefore, we postulated that clofibrate-mediated increase in NO production might be attributed to PKA/PKC signaling pathway. We examined clofibrate mediated increase in NO production/availability in renal proximal tubular cells isolated from PPAR knockout (KO) mice and the role of PKA/PKC signaling pathways using PKA 14-22 and chelerythrine, PKA and PKC inhibitors, respectively. Effect of clofibrate on eNOS and iNOS gene/protein expression was examined. Our result indicated reduced NO production in PPAR KO mice compared to the WT. Addition of clofibrate enhanced NO production in both groups, which was abolished by L-NAME. Both PKC and PKA inhibitors reduced clofibrate-mediated NO production in both groups. Clofibrate increased eNOS and iNOS mRNA and iNOS protein expression in the KO but not in WT. Clofibrate did not affect PKA/PKC protein expression in either group. Our data suggest that clofibrate effect on NO production is through induction of iNOS gene and it is PPAR-independent mechanism.

Ildikó Bata-Vidács has completed his PhD at the age of 31 in food sciences at Szent István University, Hungary. She works as a senior researcher at the Department of Applied and Environmental Microbiology, Agro-Environmental Research Institute, Budapest, Hungary. She has published more than 30 papers and book chaptes in reputed journals, from which 15 are with impact factor, and has been serving as an editorial board member for Acta Alimentaria, a peer-reviewed international journal of food sciences.

Among mycotoxins, aflatoxins are the strongest natural genotoxins. Aflatoxin B1 (AFB1) is produced by Aspergillus flavus and A. parasiticus strains. Sterigmatocystin (STC) is a precursor of aflatoxin, a not well characterized mycotoxin with only few publications. For detoxification of already contaminated substances, specific bacteria might be the solution with toxin binding abilities. In our present projects, the AFB1 and STC binding ability of lactic acid bacteria is being studied. For toxinadsorption studies stains of lactic acid bacteria were tested in MRS broth with 0.2 ppm AFB1 or STC. The binding abilities of the strains were determined after incubation from 10 min to 48 hours by measuring the toxin content of the centrifuged biomass by HPLC method with UV detection. The best AFB1 adsorption ability was found for L. plantarum TS23, L. paracasei MA2 and L. pentosus TV3 strains, binding nearly 10% of the toxin. Interestingly, for STC the binding rate was more than 20%. Neither AFB1 nor STC influenced the growth of bacterial strains at the tested concentration. It was found that 2 days of co-incubation was not required to bind the toxin, after 10 minutes, almost the same binding values were obtained. Toxin binding was detected above 107 cells/ml. There is literature on AFB1 degradation by lactobacilli, but there is no published publication on STC binding. Beyond basic research, lactobacilli as active ingredients of a biological AFB1-binding preparation could be an important innovation in feeding.

József Kukolya has completed his PhD in biological sciences at the Hungarian Academy of Sciences, Hungary. He works as head of the Department of Environmental and Applied Microbiology, Agro-Environmental Research Institute, Budapest, Hungary. He has published more than 100 papers and book chapters in reputed journals, from which 47 are with impact factor, and has been serving as chair for the Food-biotechnology Working Committee of the Hungarian Academy of Sciences, Hungary.

Despite the structure similarity of aflatoxin B1 (AFB1) and sterigmatocystin (ST), the former is a much more harmful toxin according to the published data on their biological effects. In this research, the biological effects of ST and AFB1 were examined in two different biomonitoring systems. For Escherichia coli based SOS-Chromotest, S9 rat liver P450 enzymes were used for producing genotoxic metabolic derivatives from AFB1 and ST. Equal concentrations of the toxins were measured for genotoxicity in intact form and after metabolic activation. The measured SOS-inducing potency of these toxins was almost the same: for intact AFB1, ST: 1.14 and 0.93; for metabolized AFB1, ST: 74.08 and 74.14, respectively. For the second biomonitoring system a newly developed test was used: S9-bioactivated AFB1 and ST were microinjected into zebrafish eggs. Mortality, sublethal effects, and DNA strand breaks were registered on the 5th day of the treatment. Metabolically activated sterigmatocystin caused the highest mortality and DNA strand breaks in all injected volumes. The sublethal symptoms on the embryos were the same for all treatments. The representative development dysfunctions were: moderately bent body, not well defined olfactory region, and irregular shaped lower and upper jaws. Our findings contradict the assumption that AFB1 is a more potent genotoxin than ST. In the E. coli based SOS-Chromotest, the two toxins exert the same genotoxicities. Moreover, according to the newly developed zebrafish monitoring system, ST seemed even more toxic than AFB1. These results raise the demand for more complex biomonitoring systems for mycotoxin risk assessment.