title: Combined treatment strategies for unconjugated hyperbilirubinemia in Gunn rats.
abstract: We recently demonstrated that acceleration of the gastrointestinal transit by polyethylene glycol (PEG) treats unconjugated hyperbilirubinemia in jaundiced Gunn rats. It is unclear whether acceleration of gastrointestinal transit also (partly) underlies the therapeutic effects of established hypobilirubinemic treatments or whether PEG cotreatment might enhance these effects. We treated Gunn rats with phototherapy (17 μW/cm2/nm), orlistat (200 mg/kg chow), ursodeoxycholate (5 g/kg chow), or calcium phosphate (CaP) (20 g/kg chow) either as single treatment or in combination with PEG. Three weeks of phototherapy, orlistat, ursodeoxycholic acid, or CaP treatment decreased plasma unconjugated bilirubin (UCB) levels by 47, 27, 28, and 45%, respectively (each p < 0.001), without a significant impact on gastrointestinal transit time. PEG cotreatment accelerated the gastrointestinal transit in all treatment groups, which resulted in an additive hypobilirubinemic effect of -20% and -26% (final plasma UCB -67 and -53%, respectively) in phototherapy- and orlistat-treated animals. PEG cotreatment did not enhance the hypobilirubinemic effect of ursodeoxycholic acid or CaP. We conclude that phototherapy, orlistat, ursodoxycholic acid, and CaP do not exert their hypobilirubinemic effect via acceleration of the gastrointestinal transit. PEG cotreatment enhanced the hypobilirubinemic effects of phototherapy and of orlistat treatment. Current results support a clinical trial to evaluate PEG cotreatment during phototherapy.
authors.affiliation: Department of Pediatrics, Beatrix Children's Hospital-University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Frans J C
authors.initials: FJ
authors.lastname: Cuperus
authors.forename: Arjan A
authors.initials: AA
authors.lastname: Iemhoff
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood; D002130:Calcium Phosphates / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006932:Hyperbilirubinemia / Q000188:drug therapy* / Q000628:therapy*; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D000077403:Orlistat; D010789:Phototherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011911:Rats, Gunn; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002130:Calcium Phosphates; D007783:Lactones; D011092:Polyethylene Glycols; D014580:Ursodeoxycholic Acid; D000077403:Orlistat; C020243:calcium phosphate; D001663:Bilirubin