title: Urinary excretion pattern of exosomal aquaporin-2 in rats that received gentamicin.
abstract: Urinary exosomes are nano-sized vesicles secreted into urine from all types of renal epithelial cells and are known to contain possible biomarker proteins for renal diseases. Gentamicin has been reported to decrease the level of renal aquaporin (AQP)2, which is known to be mainly expressed in renal collecting ducts and excreted into the urine via exosomes. In the present study, we investigated whether urinary exosomal AQP2 could serve as a potential biomarker for gentamicin-induced nephrotoxicity, especially collecting duct cell dysfunction. Gentamicin was given to rats intraperitoneally once every day starting on day 0. Gentamicin significantly increased the plasma creatinine concentration from day 5 and beyond. Also, gentamicin induced polyuria and a defective urine concentration mechanism on day 7, suggesting gentamicin-induced collecting duct cell dysfunction. Immunoblot analysis showed that gentamicin significantly increased urinary exosomal AQP2 excretion on day 1 but decreased it on day 7 compared with the control group. Similarly, increased excretion of exosomal tumor susceptibility gene 101 protein, frequently used as an exosome marker protein, was observed on day 1. However, gentamicin did not significantly affect the urinary excretion of exosomal tumor susceptibility gene 101 on day 7. Gentamicin slightly decreased renal AQP2 expression on day 2 and markedly decreased it on day 8. These data strongly suggest that the use of urinary exosomal AQP2 as a biomarker may allow detection of gentamicin-induced collecting duct cell dysfunction. Furthermore, urinary exosomal AQP2 might also be useful for the early detection of gentamicin-induced renal injury in addition to collecting duct injury.
authors.affiliation: Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan; and Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdeen
authors.affiliation: Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan; and.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sonoda
authors.affiliation: Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt.
authors.forename: Ragab
authors.initials: R
authors.lastname: El-Shawarby
authors.affiliation: Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan; and.
authors.forename: Saki
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Veterinary Pharmacology, University of Miyazaki, Miyazaki, Japan; and a0d302u@cc.miyazaki-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D051399:Aquaporin 2 / Q000652:urine*; D001835:Body Weight / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism*; D005839:Gentamicins / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D000099177:Tsg101 Protein
chemical_list: D000900:Anti-Bacterial Agents; D051399:Aquaporin 2; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005839:Gentamicins; D014157:Transcription Factors; D000099177:Tsg101 Protein; C492143:Pdcd6ip protein, rat
keywords: aquaporin-2; exosomes; gentamicin; nephrotoxicity; tumor susceptibility gene 101 protein