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.

Induction of Severe Chronic Hyperplastic Candidiasis in Rat by Opportunistic Infection of C. albicans through Combination of Diabetes and Intermittent Prednisolone Administration

“…Acute alloxan renal toxicity reportedly continues 1 week after treatment (Terayama et al 2017). Thus, the interval of dosing alloxan and prednisolone was extended from 2 to 4 weeks, so that diabetic rats treated with alloxan might completely recover from the effect of renal toxicity (Terayama et al 2017). The prednisolone dosage used was 10 mg/kg, the minimum lethal dosage determined in preliminary study 1.…”

Suspected lily toxicosis in a meerkat (<i>Suricata suricatta</i>): a case report

“…Acute tubular necrosis is not a specific diagnosis and can result from various nephrotoxins, such as ethylene glycol, boric acid, pharmaceutical drugs, or metals [ 5 ]. Over time, acute tubular necrosis can lead to tubular regeneration, inflammatory cell infiltration, urinary casts, and other types of tubular degeneration, with the pathological lesions changing from acute to regenerative or chronic [ 5 , 13 ]. Since in the present case, we only observed tubular necrosis, renal change was comparable to the acute phase.…”