Hyperbilirubinemia's protective effect against cisplatin nephrotoxicity in the Gunn rat.

Anti-cancer Drugs
Karri BarabasChristopher Adin

Abstract

Gunn rats, deficient in the enzyme uridine diphosphate glucuronyl transferase, were used to investigate the effects of unconjugated hyperbilirubinemia in cisplatin nephrotoxicity. The effect of bilirubin on the antineoplastic activity of cisplatin in osteosarcoma cell lines was also determined. The in vivo model involved three groups of rats (n=6 rats/group): homozygous Gunn rats (j/j), heterozygous Gunn rats (j/+), and congenic Wistar rats. On day 0, all rats were given 4 mg/kg cisplatin intraperitoneally. Blood was sampled on days 0, 3, and 5 for bilirubin, BUN, and creatinine and kidneys were taken on day 5. Cell culture was performed in four canine osteosarcoma cell lines using the average concentrations of bilirubin for homozygous Gunn rats at day 0 and 3. Bilirubin was added to cell lines alone and with cisplatin. Cell viability was assessed using the CellTiter Blue assay. Serum bilirubin levels were highly elevated in Gunn j/j, moderately elevated in Gunn j/+, and undetectable in Wistar rats at day 0. Bilirubin provided a nephroprotective effect, with significantly lower BUN and creatinine in Gunn j/j when compared with Wistar rats at day 5. Histological grading demonstrated preservation of the S3 segment in Gunn j/j whe...Continue Reading

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Citations

Aug 10, 2013·Dose-response : a Publication of International Hormesis Society·Yanling WangMichael G Irwin
Nov 15, 2019·Nature Reviews. Nephrology·Juan Carlos Q VelezLuis A Juncos
Dec 8, 2020·American Journal of Physiology. Endocrinology and Metabolism·Justin F CreedenTerry D Hinds
Mar 30, 2021·Frontiers in Pharmacology·Annalisa BiancoCristina Bellarosa
Jan 7, 2022·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClaudiu T Supuran

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