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Effect of X-ray irradiation on renal excretion of bestatin through down-regulating organic anion transporters via the vitamin D receptor in rats.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2024 Aug 25; Vol. 399, pp. 111123. Date of Electronic Publication: 2024 Jul 02. - Publication Year :
- 2024
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Abstract
- Pharmacokinetic changes induced by radiation following radiotherapy ("RT-PK" phenomenon) are of great significance to the effectiveness and safety of chemotherapeutic agents in clinical settings. The aims of this study were to clarify the organic anion transporters (Oats) involved in the "RT-PK" phenomenon of bestatin in rats following X-ray irradiation and to elucidate its potential mechanism via vitamin D signalling. Pharmacokinetic studies, uptake assays using rat kidney slices and primary proximal tubule cells, and molecular biological studies were performed. Significantly increased plasma concentrations and systemic exposure to bestatin were observed at 24 and 48 h following abdominal X-ray irradiation, regardless of oral or intravenous administration of the drugs in rats. Reduced renal clearance and cumulative urinary excretion of bestatin were observed at 24 and 48 h post-irradiation in rats following intravenous administration. The uptake of the probe substrates p-aminohippuric acid and oestrone 3-sulfate sodium in vitro and the expression of Oat1 and Oat3 in vivo were reduced in the corresponding models following irradiation. Moreover, the upregulation of the vitamin D receptor (Vdr) in mRNA and protein levels negatively correlated with the expressions and functions of Oat1 and Oat3 following irradiation. Additionally, elevated plasma urea nitrogen levels and histopathological changes were observed in rats after exposure to irradiation. The "RT-PK" phenomenon of bestatin occurs in rats after exposure to irradiation, possibly resulting in the regulation of the expressions and activities of renal Oats via activation of the Vdr signalling pathway.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024. Published by Elsevier B.V.)
- Subjects :
- Animals
Rats
Male
Rats, Sprague-Dawley
X-Rays
Organic Anion Transport Protein 1 metabolism
Organic Anion Transport Protein 1 genetics
Organic Anion Transporters metabolism
Kidney Tubules, Proximal metabolism
Kidney Tubules, Proximal radiation effects
Kidney Tubules, Proximal drug effects
Leucine analogs & derivatives
Receptors, Calcitriol metabolism
Kidney metabolism
Kidney radiation effects
Down-Regulation drug effects
Down-Regulation radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 399
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 38964638
- Full Text :
- https://doi.org/10.1016/j.cbi.2024.111123