title: Elimination of etimicin in rat kidneys and alterations of its cytotoxicity to tubular epithelial cells.
abstract: Etimicin (ETM) can accumulate in kidneys and cause tubular epithelial cell cytotoxicity. This article aims to study ETM elimination in kidneys and its nephrotoxicity, apoptosis, and histopathological insults of renal tubular epithelial cells, after repeated administration. A total of 36 rats were randomly divided into ETM-treated group and vehicle control group. Rats in ETM-treated group were treated intraperitoneally (i.p.) with 100 mg/kg/day ETM and rats in control group received physiological saline (i.p.) for 5 consecutive days. Determination of ETM concentrations accumulated in rat kidneys was carried out by high-performance liquid chromatography on the basis of derivatization with o-phthalaldehyde and by ultraviolet detector. Apoptotic renal tubular epithelial cells were identified by a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Histopathological insults in kidneys were evaluated by hematoxylin and eosin staining. On day 1 after cessation of ETM administration, the accumulation concentration was 347.50 ± 193.30 μg/g tissue; on day 15, ETM concentration became 16.71 ± 9.99 μg/g tissue. Elimination half-life of ETM in rat kidney was about 3.05 days. Apoptotic renal tubular epithelial cells induced by etimicin was recovered gradually from 1544 ± 138 n/mm(2) on day 1 to 716 ± 208 n/mm(2) on day 15. Histopathological damage was also gradually recovered from vacuolation of tubular epithelial cells as well as renal tubular edema on days 1, 3, and 7 to nearly normal on day 15. From these results, we concluded that renal tubular epithelial cell cytotoxicity induced by ETM can gradually restore with its decreasing concentration in rat kidneys.
authors.affiliation: Department of Pharmacology, General Hospital of Air Force, People's Liberation Army (PLA), Beijing, China zhdl009@126.com.
authors.forename: Z-D
authors.initials: ZD
authors.lastname: Li
authors.affiliation: Department of Pharmacology, General Hospital of Air Force, People's Liberation Army (PLA), Beijing, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, General Hospital of Air Force, People's Liberation Army (PLA), Beijing, China.
authors.forename: N
authors.initials: N
authors.lastname: Yi
authors.affiliation: Department of Pharmacology, General Hospital of Air Force, People's Liberation Army (PLA), Beijing, China.
authors.forename: F-C
authors.initials: FC
authors.lastname: Zhang
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D017208:Rats, Wistar
chemical_list: D000617:Aminoglycosides; C448680:etimicin
keywords: Etimicin; apoptosis; nephrotoxicity; renal tubular epithelial cell