Adefovir accumulation and nephrotoxicity in renal interstitium: Role of organic anion transporters of kidney
| Autor: | Yuquan Yang, Xinan Wu, Mengmeng Wei, Yan-rong Ma, Pei Wang, Yan Zhou |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
endocrine system Microdialysis Organic anion transporter 1 animal diseases viruses Organophosphonates Cmax Organic Anion Transporters Pharmacology urologic and male genital diseases Antiviral Agents 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Nephrotoxicity 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Interstitial fluid medicine Animals Tissue Distribution Rats Wistar General Pharmacology Toxicology and Pharmaceutics Kidney biology Chemistry Adenine virus diseases General Medicine Rats Probenecid Kidney Tubules 030104 developmental biology medicine.anatomical_structure biology.protein Kidney Diseases medicine.drug |
| Zdroj: | Life Sciences. 224:41-50 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2019.03.042 |
| Popis: | Common characteristics of drug induced nephrotoxicity are renal tubular and interstitial injury. Many studies have only focused on renal tubular injury. However, less is known about the effects of drugs in the renal interstitium on the nephrotoxicity. The aim of this study was to investigate the pharmacokinetics of adefovir (ADV) and the nephrotoxicity in the renal interstitium. Rats were treated with ADV alone or in combination with probenecid for 1, 7, 14, or 28 days. The renal interstitial fluid was collected by renal microdialysis. The concentration of ADV was determined by HPLC-MS/MS. Nephrotoxicity was evaluated by biochemical parameters or histological analysis. The results showed that organic anion transporters (OATs) inhibitor probenecid significantly increased the area under concentration-time curves (AUC) and peak concentration (Cmax) of ADV in the renal interstitium, while the clearance (CL) in the renal interstitium was decreased in the ADV plus probenecid group compared to the ADV groups. After long-term treatment, interstitial fibrosis was present in the ADV plus probenecid group, whereas no trace of that could be detected in the ADV groups. Furthermore, a decrease was observed in the expression of OATs/Oats, which was dependent upon the concentrations and time of ADV treatment. In conclusion, it is possible that ADV could be accumulated in the interstitium when Oats were inhibited, which could cause renal interstitial fibrosis. Simply reducing cell uptake in long-term treatment might not be an effective method to protect against chronic nephrotoxicity. |
| Databáze: | OpenAIRE |
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