An Immunohistochemical Investigation of Renal Phospholipidosis and Toxicity in Rats. (September 2017)

• Record Type: Journal Article
• Authors: Ma, Jing Ying; Snook, Sandra; Garrovillo, Sheryl; Johnson, Charles; La, David
• Is Part Of: International journal of toxicology. Volume 36:Number 5(2017)
• Page Start: 386
• Page End: 394
• Publication Date: 2017-09
• Subjects: immunohistochemistry -- kidney -- phospholipidosis -- LAMP-2 -- KIM-1; Toxicology -- Periodicals; 615.9005
• DOI: 10.1177/1091581817726040
• Languages: English
• ISSNs: 1091-5818

Abstract

Immunohistochemical staining for the lysosome-associated membrane protein 2 (LAMP-2) has been proposed previously as an alternative to electron microscopy to identify hepatic phospholipidosis. This study used LAMP-2 immunohistochemistry (IHC) to diagnose phospholipidosis in rats exhibiting renal tubular injury. Rats were administered toreforant, a histamine H4 receptor antagonist by oral gavage at a dose of 3, 10, or 100 mg/kg/d for 6 months. Hematoxylin and eosin staining revealed renal tubular epithelial cell vacuolation, hypertrophy, degeneration, and luminal dilation in the 100 mg/kg/d group animals. Renal tubular injury was confirmed using kidney injury marker 1 (KIM-1) IHC. The involvement of phosopholipidosis in the renal injury was investigated by LAMP-2. Adipophilin IHC was included to differentiate phospholipidosis from lipidosis. Increased LAMP-2 staining was observed in the 100 mg/kg/d group animals when compared to vehicle group animals. Lysosome-associated membrane protein-2 staining was most prominent in the outer stripe of the outer medulla where KIM-1 staining was also most prominent. By contrast, adipophilin staining was not increased. Phospholipidosis was also confirmed by electron microscopy. These data support the use of LAMP-2 IHC as a diagnostic tool and suggest an association between phospholipidosis and the renal tubular injury caused by toreforant.