Central metal determines pharmacokinetics of chlorophyll-derived xenobiotics.

Chlorophyll derivatives are potentially dangerous xenobiotics of dietary origin. The interactions of water-soluble derivatives of chlorophyll a with the animal organism were investigated using chlorophyllide a and its Zn-substituted analogue as model xenobiotics. The chlorophyllides were administered to tumor-bearing mice and their uptake, distribution, and clearance were compared. The centrally bound metal determines important aspects of the in vivo behavior of metallochlorophyllides as xenobiotics. The uptake and clearance of chlorophyllide a were significantly faster than those of [Zn]-chlorophyllide a. Chlorophyllide a showed some tissue selectivity, while [Zn]-chlorophyllide a was uniformly distributed among tissues. Interestingly, the tissue levels of the latter compound were ten times higher than those of the Mg-derivative. These differences indicate that [Zn]-chlorophyllide a, in contrast to chlorophyllide a, is only weakly recognized by the system of active transport of xenobiotics and by enzymes involved in chlorophyll metabolism. The dependence of chlorophyllide pharmacokinetics on the central metal is of great relevance to chlorophyll-based phototherapy.