Ultrastructural evaluation of urine alkalinization versus hydration on colistin-induced nephrotoxicity


Korucu B., Unal I., Pekcan M., İNKAYA A. Ç., Yeter H. H., ÇETİNKAYA M. A., ...Daha Fazla

Human and Experimental Toxicology, cilt.38, sa.12, ss.1366-1377, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 12
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1177/0960327119862339
  • Dergi Adı: Human and Experimental Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1366-1377
  • Anahtar Kelimeler: Colistin, nephrotoxicity, urine alkalinization, urine density
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Objectives: Colistin is a vital antibiotic used in multidrug-resistant infections. Its most important side effect is nephrotoxicity. Colistin is a weak acid. This study aims to evaluate whether urine alkalinization is protective in the nephrotoxicity of colistin. Methods: Twenty-eight male Sprague-Dawley rats were divided into groups. Group I (n = 4) was injected with intramuscular distilled water twice a day for 7 days. Group II (n = 8) was injected with 750,000 IU/kg/day colistin for 7 days. Group III (n = 8) was injected with the same dose of colistin after their urinary pH was ≥7 through the addition of bicarbonate in their drinking water. Group IV (n = 8) was injected with the same dose of colistin after their urine density fell below 1010 through the addition of NaCl molds in their food and 12.6 mg/L NaCl in their drinking water. Results: According to tubular degenerations (scored 0–5), group I scored 0, group II scored 4.25, group III scored 2, and group IV scored 1.5. In groups III and IV, protection was achieved (p = 0.001). The bicarbonate group was not superior to the NaCl group (p = 0.789). In transmission electron microscopy, group III had more microvilli integrity and autophagic vacuoles compared to group IV. Group IV had mitochondrial swelling and cristae lysis. A lower urine density was related to lower tubular scores (p = 0.001). Conclusions: Colistin was highly nephrotoxic without protection. Light microscopy findings revealed that urinary alkalinization and NaCl hydration were similarly protective. Urine alkalinization further prevents ultrastructural changes as revealed by electron microscopy.