Acute nephrotoxic potential of acrylonitrile in Fischer-344 rats

In view of its very limited information, we have evaluated the acute nephrotoxic potential of acrylonitrile (ACN) in male Fischer-344 rats. ACN was given i.p. in saline to groups of 6 rats at doses 0, 10, 20, 40, 60 and 80 mg/kg. Urines were collected for 48 h and the animals were sacrificed at 24 and 48 h after the exposure. Significant increased levels of urinary volumes, glucose as well as increased levels of N-acetyl-beta-D-glucosaminidase (NAG), were observed at higher dose levels of ACN at 24 h. Light microscopy showed an increase in size and number of renal lysosomes or dense bodies at 60 mg ACN per kg after 48 h. Ultrastructural studies showed increase of dense bodies and endocytotic vacuoles at the same higher dose of ACN at 48 h. Autophagic vacuole formation as well as dilatation of endoplasmic reticulum membranes was also noted at the higher dose level. Acute inhalation exposure to ACN at 200 ppm for 4 h produced increases in the urinary volumes, proteins, glucose, gamma-GT and NAG 24 h after the exposure. These results demonstrate that ACN could produce acute nephrotoxic insult preferably at the proximal tubular region of the rat kidney.