In this essay, the hypothesis that biliverdin pigment plays an antioxidant role in the avian eggshell is proposed. Due to its ability to scavenge free radical species and to reduce mutation, biliverdin potentially counteracts the oxidative action of pathogens that penetrate the eggshell and/or protects the shell membrane from oxidation, thus promoting the proven antioxidant and antimicrobial capacities of the shell membrane itself. Additionally, biliverdin may be able to inhibit viral replication in the eggshell due to its (...) ascribed antiviral properties. Moreover, previous results in other taxa leave open the question of whether biliverdin can be absorbed by the embryo from the eggshell and play a role in embryogenesis. These mechanisms of antioxidant action of eggshell biliverdin remain totally unexplored in birds and in other oviparous animals. The main assumptions and predictions of the antioxidant hypothesis are developed, and directions for future research are proposed. (shrink)

Graphical AbstractThe antioxidant hypothesis proposes that the blue-green pigment found in many birds’ eggs provides a direct benefit to the developing embryo through its antioxidant-like properties. Such protection is feasible if the pigment transfers to the eggshell membrane or inside the egg. This newly proposed hypothesis provides a range of intriguing possibilities for future tests.

Carbon monoxide (CO), a product of organic oxidation processes, arises in vivo during cellular metabolism, most notably heme degradation. CO binds to the heme iron of most hemoproteins. Tissue hypoxia following hemoglobin saturation represents a principle cause of CO‐induced mortality in higher organisms, though cellular targets cannot be excluded. Despite extreme toxicity at high concentrations, low concentrations of CO can confer cytoprotection during ischemia/reperfusion or inflammation‐induced tissue injury. Likewise, heme oxygenase, an enzyme that produces CO, biliverdin and iron, as (...) well as a secondary increase in ferritin synthesis, from the oxidation of heme, can confer protection in vivo and in vitro. CO has been shown to affect several intracellular signaling pathways, including guanylate cyclase, which generates guanosine 3′:5′ cyclic monophosphate and the mitogen‐activated protein kinases (MAPK). Such pathways mediate, in part, the known vasoregulatory, anti‐inflammatory, anti‐apoptotic and anti‐proliferative effects of this gas. Exogenous CO delivered at low concentrations is showing therapeutic potential as an anti‐inflammatory agent and as such can modulate numerous pathophysiological states. This review will delve into the biological significance and medical applications of this gas molecule. BioEssays 26:270–280, 2004. © 2004 Wiley Periodicals, Inc. (shrink)