Increased renal fibrosis and expression of renal phosphatidylinositol 4-kinase-beta and phospholipase C(gamma1) proteins in piglets exposed to ochratoxin-A.
Endemic nephropathy has been linked to exposure of ochratoxin-A (OA) in grains and animal products. The underlying events surrounding this form of renal injury are not well known, partly due to the lack of a suitable animal model of the disease. Therefore, in this study, a pig model of OA-induced renal injury was established and used to examine whether elements of the phosphoinositide signalling pathway are altered in this disease. Weanling piglets were fed diets containing 0, 2, and 4 ppm OA for 6 weeks. Serum creatinine and urea and renal fibrosis were monitored biweekly using serial blood samples and renal biopsies. At termination, the protein levels of renal phosphatidylinositol 4-kinase-beta (PtdIns4Kbeta) and phospholipase C(gamma1) (PLC(gamma1)) were determined using immunoblotting and scanning densitometry. Serum creatinine was elevated by 2 weeks and renal fibrosis was elevated by 4 weeks at both levels of inclusion of OA. At the end of the experimental period, kidney size and water content were elevated, as were the protein levels of renal PtdIns4Kbeta and PLC(gamma1) in OA-exposed animals. Therefore, serial biopsies can be used to track changes in renal pathology in the OA-exposed piglet. We conclude that this is a useful model for OA-induced renal injury in which the underlying molecular events associated with this form of renal injury can be studied.
Aukema
H M
HM
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada.
House
J D
JD
Bankovic-Calic
N
N
Ogborn
M R
MR
D019870:1-Phosphatidylinositol 4-Kinase / Q000096:biosynthesis* / Q000276:immunology; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005355:Fibrosis / Q000139:chemically induced* / Q000201:enzymology; D005557:Formaldehyde; D015151:Immunoblotting / Q000379:methods; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009793:Ochratoxins / Q000494:pharmacology*; D016612:Paraffin Embedding; D051966:Phospholipase C gamma; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D014020:Tissue Extracts / Q000737:chemistry; D016707:Tissue Fixation; D010738:Type C Phospholipases / Q000096:biosynthesis* / Q000276:immunology
D009793:Ochratoxins; D014020:Tissue Extracts; C025589:ochratoxin A; D005557:Formaldehyde; D019870:1-Phosphatidylinositol 4-Kinase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma