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- _3 value "Interestingly, the HO effector molecules biliverdin/bilirubin and CO have also been implicated in the modulation of a range of signaling pathways, including the cGMP and MAPK system, by which they may modulate inflammatory processes and also be involved in ROS-mediated signaling (Adeagbo, 1997; Siow et al., 1999; Otterbein et al., 2000; Nath et al., 2001b). It is likely that HO effector molecules bilirubin and CO, similar to anti-oxidants and NO (De Caterina et al., 1995), play a role in the regulation of ROS-mediated pathways, since HO-1 knockout mice show increased nuclear staining of NF-B after exposure to hemoglobin, compared with control mice (Nath et al., 2001b)." provenance.