ABSTRACT
It has been demonstrated that some strains of Bacillus coagulans can survive extremes of heat, acidity of the stomach, and bile acids, to which commonly consumed probiotics are susceptible. A toxicological safety assessment was performed on a proprietary preparation of B. coagulans - GanedenBC(30) - a novel probiotic. Seven toxicologic studies were conducted and included: in vitro bacterial reverse mutation assay; in vitro chromosomal aberration assay; micronucleus assay in mice; acute and 90 day subchronic repeated oral toxicity studies were conducted in Wistar Crl:(WI) BR rats; acute eye and skin irritation studies were conducted in rabbits. The results of this toxicological safety assessment indicate that GanedenBC(30)B. coagulans does not demonstrate mutagenic, clastogenic, or genotoxic effects. Furthermore, the results of the acute and 90-day subchronic oral toxicity studies in rats resulted in the conclusion of a NOAEL greater than 1000 mg/kg per day. Since the concentration of the cell mass used in the 90-day study was 1.36 x 10(11) CFUs/g, this corresponds to 95.2 x 10(11) CFUs for a 70 kg human and since the suggested human dose is in the range of 100 x 10(6) to 3 x 10(9) CFUs, this gives a safety factor ranging from 3173 to 95,200 times. Based upon scientific procedures and supported by history of use, GanedenBC(30) is considered safe for chronic human consumption.
Subject(s)
Bacillus/physiology , Probiotics/adverse effects , Animals , Blood Chemical Analysis , Chromosome Aberrations/drug effects , Eye/drug effects , Eye/pathology , Food , In Vitro Techniques , Irritants/toxicity , Male , Mice , Mice, Inbred BALB C , Micronucleus Tests , Mutagenicity Tests , No-Observed-Adverse-Effect Level , Rabbits , Rats , Rats, Wistar , Safety , Skin/drug effects , Skin/pathology , Weight Gain/drug effectsABSTRACT
We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARgamma2 gene expression.
