Albumin administration protects against bilirubin-induced auditory brainstem dysfunction in Gunn rat pups

<p>Background Free bilirubin (Bf), the unbound fraction of unconjugated bilirubin (UCB), can induce neurotoxicity, including impairment of the auditory system, which can be assessed by brainstem auditory evoked potentials (BAEPs). We hypothesized that albumin might reduce the risk of neurotoxicity by decreasing Bf and its translocation into the brain. AimTo determine the effects of albumin on BAEPs and brain bilirubin content in two Gunn rat pup models of acute hyperbilirubinemia. MethodsWe used Gunn rat pups, which have a deficiency of the bilirubin-conjugating enzyme UGT1A1. We induced haemolysis by injection of phenylhydrazine (phz) into 14-days old pups. Subsequently, pups were treated with either i.p. human serum albumin (HSA; 2.5g/kg; n=8) or saline (control, n=8). We induced acute neurotoxicity by injecting 16-days old pups with sulphadimethoxine (sulpha) and treated them with either HSA (n=9) or saline (control, n=10). To assess bilirubin neurotoxicity, we used the validated BAEP method and compared relevant parameters; i.e. peak latency values and interwave interval (IWI) between peak I and peak II, a marker of acute neurotoxicity. ResultsPhz and sulpha significantly increased IWI I-II by 26% and 29% (P</p>

Optimizing Exchange Transfusion for Severe Unconjugated Hyperbilirubinemia: Studies in the Gunn Rat

Background: Severe unconjugated hyperbilirubinemia carries the risk of neurotoxicity. Phototherapy (PT) and exchange transfusion (ET) are cornerstones in the treatment of unconjugated hyperbilirubinemia. Studies to improve ET efficacy have been hampered by the low application of ET in humans and by the lack of an in vivo model. The absence of an appropriate animal model has also prevented to determine the efficacy of adjunct or alternative treatment options such as albumin (Alb) administration. Aim: To establish an in vivo model for ET and to determine the most effective treatment (combination) of ET, PT and Alb administration. Methods: Gunn rats received either PT, PT+Alb, ET, ET+PT, ET+PT+Alb or sham operation (each n = 7). ET was performed via the right jugular vein in similar to 20 min. PT (18 mu W/cm(2)/nm) was started after ET or at T-0. Albumin i.p. injections (2.5 g/kg) were given after ET or before starting PT. Plasma unconjugated bilirubin (UCB), plasma free bilirubin (Bf), and brain bilirubin concentrations were determined. Results: We performed ET in 21 Gunn rats with 100% survival. At T-1, ET was profoundly more effective in decreasing both UCB -44%, p Conclusions: We optimized ET for severe unconjugated hyperbilirubinemia in the Gunn rat model. Our data indicate that ET is the most effective treatment option, in the acute as well as the follow-up situation

Beyond plasma bilirubin: the effects of herapy and albumin on brain bilirubin levels in Gunn rats.

Item does not contain fulltex

Brain bilirubin levels.

<p>Effects of sham transfusion (controls), phototherapy (PT), albumin (Alb), an exchange transfusion (ET) or a combination ofn these on brain bilirubin levels in Gunn rats. For experimental setup, kindly refer to the Methods section. Values are mean ± SD. *p<0.05 compared to controls. #p<0.01 compared to PT. $p<0.05 compared to ET and ET+PT.</p

Plasma UCB and Bf concentrations after 1 h.

<p>Acute effects of sham transfusions (control) or phototherapy (PT), albumin (Alb), an exchange transfusion (ET), or a combination of these on plasma UCB concentrations (<b>A</b>) and plasma Bf concentrations (<b>B</b>) in Gunn rats. Rats were randomized to receive sham transfusions (control) or an exchange transfusion (ET), and were subsequently treated with phototherapy (PT), albumin (Alb) or the combination of PT+Alb. Values are mean ± SD. *p<0.001 compared to controls. #p<0.05 compared to PT. $p<0.05 compared to PT+Alb.</p

Course of plasma UCB and Bf concentrations after exchange transfusion.

<p>Course of plasma UCB concentrations (<b>A</b>) and plasma Bf concentrations (<b>B</b>) after sham transfusions (control) or an exchange transfusion (ET) in Gunn rats. Rats were randomized to receive sham transfusions (control) or an exchange transfusion (ET). Values are mean ± SD. *p<0.01 compared to controls. #p<0.001 ET: T₀ compared to T₁.</p

Plasma UCB and Bf concentrations after 48 h.

<p>Long-term effects of an exchange transfusion (ET), with or without the combination of phototherapy (PT), or albumin (Alb), on plasma UCB concentrations (<b>A</b>) and plasma Bf concentrations (<b>B</b>) in Gunn rats. Rats were randomized to receive an exchange transfusion (ET), and were subsequently treated with phototherapy (PT), albumin (Alb) or the combination of PT+Alb. Values are mean ± SD. *p<0.01 compared to ET. #p<0.05 compared to ET+PT.</p