Activation of Alternative Bilirubin Clearance Pathways Partially Reduces Hyperbilirubinemia in a Mouse Model Lacking Functional Ugt1a1 Activity.

ABSTRACT: Bilirubin is a heme catabolite and Ugt1a1 is the only enzyme involved in the biological elimination of bilirubin. Partially functional or non-functional Ugt1a1 may result in neuronal damage and death due to the accumulation of unconjugated bilirubin in the brain. The understanding of the role of alternative bilirubin detoxification mechanisms that can reduce bilirubin toxicity risk is crucial for developing novel therapeutic strategies. To provide a proof-of-principle showing whether activation of alternative detoxification pathways could lead to life-compatible bilirubin levels in the absence of Ugt1a1 activity, we used Ugt1^-/- hyperbilirubinemic mice devoid of bilirubin glucuronidation activity. We treated adult Ugt1^-/- mice with TCPOBOP, a strong agonist of the con

SUBMITTER: Banerjee B 

PROVIDER: S-EPMC9505366 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature