Safety evaluation of chicken breast extract containing carnosine and anserine.

Chicken breast extract (CBEX) is obtained via hot water extraction of chicken breast and contains among its primary constituents carnosine and anserine, which are histidine-containing dipeptides present in the muscle tissues of most vertebrate species. Dietary intake of CBEX has been previously shown to buffer hydrogen ions formed during high-intensity exercise in human skeletal muscle cells, thereby inhibiting a decrease in muscle cell pH and subsequent muscle fatigue. The objective of this paper is to report the results of safety studies completed on CBEX. CBEX was determined to have an oral LD(50) value of more than 6000 mg/kg body weight in rats. Gavage doses of 500 or 2000 mg CBEX/kg body weight/day administered to rats for 90 days produced no toxicologically significant, dose-related, differences between control and treated animals with respect to body weight gain, food consumption, behavioral effects, hematological and clinical chemistry parameters, absolute and relative organ weights, or gross and microscopic findings. In the presence or absence of metabolic activation, CBEX exerted no mutagenic activity in the Ames assay conducted in various strains of Salmonella typhimurium and Escherichia coli. The results of these studies support the safety of CBEX as a potential dietary source of carnosine and anserine.

L-methionine induces stage-dependent changes of differentiation and oxidative activity in sea urchin embryogenesis.

This study was to investigate developmental toxicity of some selected low molecular weight antioxidants, by utilising sea urchin embryos and gametes as model system. Sea urchin embryos or sperm were exposed at different developmental stages to L-methionine or some selected low molecular weight antioxidants: a) N-acetylcysteine; b) L-carnosine; c) L-homocarnosine, and d) L-anserine. L-methionine displayed developmental toxicity at levels > or = 10(-5) M, whereas the other agents tested were mostly active at levels > or = 10(-4) M. When embryos were exposed to 10(-4) M L-methionine or N-acetylcysteine at different developmental stages, the most severe effects were exerted by early exposures (0 to 2 hr after fertilisation), whereas later exposures turned to lesser or no effects. Cytogenetic analysis of L-methionine-exposed embryos showed a significant mitogenic effect and increase of mitotic aberrations. Fertilisation success was decreased by L-methionine (10(-6) M to 10(-3) M) added at the moment of fertilisation, with increasing developmental and cytogenetic abnormalities in the offspring. The formation of reactive oxygen species in embryos and gametes was determined by: a) analysing the DNA oxidative product, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and b) luminol-dependent chemiluminescence. The results showed that: 1) 8-OHdG levels were increased during embryogenesis; 2) fertilisation was associated with a double-wave luminol-dependent chemiluminescence emission; 3) luminol-dependent chemiluminescence was maximal in cleavage, declining down to zero in plutei, and 4) an embryotoxic L-methionine or N-acetylcysteine level (10(-4) M) turned to a decrease in reactive oxygen species formation. The data suggest that L-methionine- or N-acetylcysteine-induced developmental toxicity is confined to early stages. A role for oxidative activity is suggested in modulating cell differentiation and embryogenesis, consistent with antioxidant-induced damage to early life stages.