Biliary and urinary excretion rates and serum concentration changes of four bilirubin photoproducts in Gunn rats during total darkness and low or high illumination

Abstract

On cycled exposure of Gunn rats to total darkness and low and high illumination, biliary excretion rates of (EZ)- and (ZE)-bilirubin and (EZ)-cyclobilirubin increased up to approx. 10-fold from the mean basal values of 1.2 and 0.2 microgram/h to the mean maximum values of 25.2 and 4.2 micrograms/h respectively, and at the same time those of (EE)-bilirubin and (EE)-cyclobilirubin also increased, but at very much lower rates than those of the first-mentioned two. During the low illumination only (EZ)- and (ZE)-bilirubin and (EZ)-cyclobilirubin appeared in the urine; during the high illumination (EE)-bilirubin and (EE)-cyclobilirubin also appeared, showing a similar excretion pattern to that observed in the bile, but the total urinary excretion rates were lower than the total biliary excretion rates. The serum bilirubin concentrations fell gradually to lower values, accompanied by an increment in (EZ)- and (ZE)-bilirubin, but (EZ)-cyclobilirubin was not detected. It is concluded that during phototherapy the predominant pathway for the removal of bilirubin from the body in the Gunn rat is by biliary excretion of the geometric photoisomers (EZ)- and (ZE)-bilirubin, derived from Z----E isomerization, and the structural photoisomer (EZ)-cyclobilirubin, formed from intramolecular endo-vinyl cyclization.

Wavelength Dependence of the Geometric and Structural Photoisomerization of Bilirubin Bound to Human Serum Albumin

“…Gunn rats geometric photoisomerization is the main contributor [21], The causes of these marked species-dependent differences arc considered to be the following. Complexing of bilirubin with scrum albumin has a species-dependent influence on bilirubin photoisomerization [7,11,12,22], The rela tive rate constants in photoisomerization reaction of bilirubin bound to human serum albumin, except those for the rate of conver sion from (ZZ)-bilirubin into (EZ)-bilirubin, proved to be much larger than those for bili rubin bound to rat serum albumin [7].…”

Phototherapy with blue and green mixed-light is as effective against unconjugated jaundice as blue light and reduces oxidative stress in the Gunn rat model

“…In addition, this reaction is promoted by green light irradiation at around 510 nm [15]. Although Gunn rats mainly excrete ZE-bilirubin, they also produce and excrete lumirubin [16].…”

Phototherapy for neonatal hyperbilirubinemia

“…(a) Pattern of excretion of four bilirubin photoisomers into bile in the Gunn rat ( n = 5) vs level of illumination: (○) ( EZ )‐/( ZE )‐bilirubin; (●) ( EZ )‐cyclobilirubin; (□) ( EE )‐bilirubin; (■) ( EE )‐cyclobilirubin. Reproduced with permission from Onishi S, et al 1984 (b) Human newborn infant: effect of phototherapy on (○) ( ZZ )‐bilirubin and (●) ( EZ )‐cyclobilirubin‐ IX α concentration in duodenal aspirate. Reproduced with permission from Onishi et al 1984…”

“…22 The results using Gunn rats, however, differed from those in human newborn infants. The main form of bilirubin excreted into bile during phototherapy was the geometric isomer in Gunn rats 22,31 and the structural isomer in human newborn infants. 32 This was proved by analyzing the bilirubin photoisomers in bile during photoirradiation.…”