The role of α2u-globulin in ochratoxin A induced renal toxicity and tumors in F344 rats

Abstract

The mycotoxin ochratoxin A (OTA) was shown to be a potent kidney carcinogen in rats demonstrating a marked sex difference in the response. Compared to female rats, male rats had a 10-fold higher incidence of kidney carcinomas. The objective of this study was to investigate whether this sex difference in tumor response is due to an exacerbation of effect resulting from the interaction of the male rat specific urinary protein h2u-globulin (h2u) with OTA. Male and female rats were treated by oral gavage with OTA (1 mg/kg per day), D-limonene (dL; 1650 mg/kg per day) as a positive control or corn oil for 7 consecutive days. OTA induced severe renal lesions predominantly in the P 3 region of the proximal tubules. The lesions consisted of necrotic cells and cell exfoliations. No hyaline droplets were found in the P 2 segment following OTA treatment, whereas dL induced the expected accumulation of droplets. The results suggest that OTA induced kidney lesions are in all characteristic points different from the known h2u-nephropathy induced by dL. Based on these experiments the male rat specific protein h2u does not seem to be involved in the mechanism(s) leading to the high tumor incidence observed in OTA exposed male rats.

Ochratoxin A Toxic Effect on Rat Kidneys and the Potential Protective Effect of Ginseng: Histopathologic, Histochemical, and Image Analysis Morphometric Studies

“…In contrary with Rasonyi et al [28], necrotic cells and cell exfoliations in rat kidney treated with ochratoxin were noticed. No hyaline casts were noticed.…”

Effects of repeated ochratoxin exposure on renal cells in vitro

“…Indeed many similarities, including atrophic proximal tubules and fibrotic tissue, have been reported between the later stages of BEN and mycotoxin-induced porcine nephropathy (MPN) (Stoev, 1998). Rásony and co-workers reported a similar OTAinduced loss of proximal tubular cells, accompanied with increased regenerative processes, in rats following oral OTA exposure (Rásonyi et al, 1999).…”

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

“…This accumulation initiates a sequence of events that appears to lead to nephropathy and renal tumor formation (Rodgers and Baetcke, 1993). Even though it has been demonstrated that OTA kidney lesions are different from the α2u-nephropathy in all characteristic points (Rasonyi et al, 1999) and that OTA also causes renal tumors in male mice (Bendele et al, 1985), Mantle and Nagy (2008) suggested that the α2u-globulin could act as a specific OTA carrier that increases proximal tubule exposure to the mycotoxin in male rats. However, this has not been demonstrated experimentally.…”