title: Acute alloxan renal toxicity in the rat initially causes degeneration of thick ascending limbs of Henle.
abstract: Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristics relevant to acute renal toxicity following AL administration. Rats were intravenously treated with AL. Eight hours after AL treatment, aquaporin 1-negative and Na/K pump-positive thick ascending limbs of Henle (TAL) were degenerated in the outer medulla. These tubular lesions progressed from the outer medulla to the cortex. At day 2 after AL treatment, the lesions reached a peak, then both proximal and distal tubules also showed degeneration and necrosis, and tubular regeneration was seen in TAL. Immunohistochemically, damaged tubular epithelium included slightly enlarged prohibitin-positive granules, but it expressed no GLUT2, which is an AL transporter. Ultrastructurally, cytoplasmic and mitochondrial swelling was detected in degenerated cells of TAL. These findings suggest that AL initially causes degeneration of TAL, and induces mitochondrial and cellular damage in the tubular epithelium without involving GLUT2.
authors.affiliation: Laboratory of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Terayama
authors.affiliation: Laboratory of Clinicopathological Therapeutics, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Laboratory of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsuura
authors.affiliation: Laboratory of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Ozaki
keywords: acute renal toxicity; alloxan; rat; tubular necrosis