Effect of combined treatment with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin and phototherapy on bilirubin metabolism in the jaundiced gunn rat

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin, a potent inducer of microsomal cytochrome P448‐dependent monoxygenases, and phototherapy both accelerate bilirubin metabolism and decrease jaundice in Gunn rats. The effects of combined treatment with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin and light were studied in these rats by applying phototherapy for 65 hr, beginning 5 days after induction with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin. 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin pretreatment caused a 75% decline in plasma bilirubin in 5 days, with no change thereafter, whether or not the rats were exposed subsequently to phototherapy. In the uninduced rats, plasma bilirubin levels declined by 55% after 40 hr of phototherapy. As determined by [¹⁴C]bilirubin kinetics, both 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin and phototherapy increased fractional bilirubin turnover and decreased the total bilirubin pool. In the 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐induced rats, the contracted bilirubin pool shifted from skin to liver, but these tissue pools did not change further during phototherapy. By contrast, in uninduced rats, phototherapy decreased the cutaneous bilirubin pool, which is the main target of phototherapy. 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin was more effective than phototherapy in diminishing plasma bilirubin levels and the total bilirubin pool, but the combined treatment (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin followed by phototherapy) was no more effective than 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin alone.