Transfer and Metabolism of Pyrrolizidine Alkaloids from Jacobaea vulgaris Gaertn. in Ruminants

Abstract

Pyrrolizidine alkaloids (PA/PANOs) are compounds found in over 6000 plant species, including Jacobaea vulgaris Gaertn. (common ragwort). Upon hepatic activation, these protoxins exhibit hepatotoxic and carcinogenic properties. This study aimed to investigate the ruminal metabolism and tissue transfer of PA/PANOs found in Jacobaea vulgaris Gaertn. in ruminants to better assess the uptake of PA/PANOs by grazing livestock. This study investigated the ruminal metabolism of cyclic diesters. The nine major free base pyrrolizidine alkaloids (PA) and corresponding N-oxides (PANO) from Jacobaea vulgaris Gaertn. were examined in vitro with rumen liquid from cattle. The results confirmed that all PANOs were rapidly reduced to the corresponding PAs, and most PAs were swiftly metabolized. Compounds such as jacobine, jaconine, and senkirkine exhibited slow elimination, while jacoline remained almost stable. For the first time, it was shown that cyclic diesters are reduced in the rumen to 1,2-saturated metabolites. This reduction is crucial, as the 1,2-double bond is structurally necessary for the toxification of PAs in the liver. Analysis of ruminal fluids from in vivo feeding studies with cattle, sheep, and goats confirmed the in vitro results. Samples from these in vivo feeding studies also revealed a low transfer of PA/PANOs into the muscle tissue of the animals, with mostly jacoline, jacobine, and jaconine being detectable, consistent with the elimination rate observed in vitro in the rumen. Therefore, the risk of exposure to PA/PANOs through the consumption of meat from ruminants exposed to doses of PA/PANO similar to those in this study appears to be low. Moreover, the reported average levels of PA/PANO contamination in feed used in Europe are significantly lower than the doses used in this study. Interestingly, the metabolites identified in the rumen were not detected in the muscle tissue. A huge amount of these metabolites was detected in the feces of the animals, suggesting that these metabolites may not pass the intestinal barrier or are further transformed in other processes in the body of the animals. This study demonstrates that the rumen plays a crucial role in detoxifying PA/PANOs. This filtering function substantially reduces the uptake of PA/PANOs within the animal’s body, presumably decreasing the health threat posed by these substances to ruminants. Additionally, ruminal activities result in a low transfer of PA/PANOs into animal products such as meat, thereby lowering the risk of exposure through meat consumption.