Establishment of an experimental rat model of tacrolimus-induced kidney injury accompanied by interstitial fibrosis

Rao Fu, Soichiro Tajima, Tomohiro Shigematsu, Mengyu Zhang, Akihiro Tsuchimoto, Nobuaki Egashira, Ichiro Ieiri, Satohiro Masuda

研究成果: Contribution to journalArticle査読

抄録

Nephrotoxicity is the major adverse reaction to tacrolimus; however, the underlying mechanisms remain to be fully elucidated. Although several tacrolimus-induced nephrotoxicity animal models have been reported, most renal injury rat models contain factors other than tacrolimus. Here, we report the development of a new nephrotoxicity with interstitial fibrosis rat model induced by tacrolimus administration. Thirty Wistar rats were randomly divided into four groups: sham-operated (Sham), vehicle-treated ischemia reperfusion (I/R) injury (IRI), tacrolimus treated (TAC) and tacrolimus treated I/R injury (TAC + IRI). Rats subjected to IR injury and treated with tacrolimus for 2 weeks showed higher serum creatinine (Scr), blood urea nitrogen (BUN), serum magnesium (Mg) and serum potassium (K), indicating decreased renal function. In addition, tacrolimus treatment combined with IR injury increased histological injury (tubular vacuolation, glomerulosclerosis and interstitial fibrosis), as well as α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and kidney injury molecule-1 (KIM-1) expression in the renal cortex. In summary, we have developed a tacrolimus-induced kidney injury rat model with interstitial fibrosis within 2 weeks by creating conditions mimicking renal transplantation via tacrolimus administration following ischemia-reperfusion.

本文言語英語
ページ(範囲)43-50
ページ数8
ジャーナルToxicology Letters
341
DOI
出版ステータス出版済み - 5 1 2021

All Science Journal Classification (ASJC) codes

  • 毒物学

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