N. Gyrd‐Hansen

Renal enzyme activities in experimental ochratoxin A‐induced porcine nephropathy: Diagnostic potential of phosphoenolpyruvate carboxykinase and gamma‐glutamyl transpeptidase activity

Enzyme activities have been measured in needle biopsies from kidneys of pigs fed 1 ppm or 0.2 ppm of ochratoxin A for 1-5 wks. After feeding 1 ppm toxin for 1 wk, the activity of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) was decreased by 40% and remained inhibited until the termination of the experiment (5 wk). The activity of gamma-glutamyl transpeptidase, a brush-border enzyme found in the proximal tubules, was reduced to a similar degree and remained inhibited. The activities of hexokinase, a cytosolic enzyme of general distribution in the nephron, and phosphate-dependent glutaminase, a distal tubule enzyme, were not affected. The biopsy results were confirmed by measurements in renal slices taken at the termination of the experiment, except that biopsy samples showed more variation in enzyme activity and a lower PEPCK activity. A guinea pig antibody against the cytosolic form of PEPCK was used to demonstrate that the mitochondrial form of the enzyme, which accounts for a considerable part of the total cellular activity, was not affected by ochratoxin A. When mitochondrial PEPCK activity present in the cytosolic fraction was accounted for, ochratoxin A was found to reduce PEPCK activity by 70-80%. The increase of ochratoxin A exposure from zero through 0.2 ppm to 1 ppm, which resulted in dose-dependent activity decrease of PEPCK and gamma-glutamyl transpeptidase, was accompanied by dose-dependent decrease of renal function, as measured by a reduction of maximal tubular excretion of para-aminohippurate per clearance of inulin (TmPAH/CIn) and an increase in glucose excretion. This suggest that these enzymes are sensitive indicators of ochratoxin A-induced porcine nephropathy. Assuming that porcine nephropathy represents a valid model of endemic (Balkan) nephropathy in humans, the measurement of cytosolic PEPCK and gamma-glutamyl transpeptidase activity in the kidney could be a sensitive test for ochratoxin A-induced disease in humans.

Metabolism of sulfadiazine in neonatal and young pigs: Comparative in vivo and in vitro studies

Metabolism of sulfadiazine (SDZ) was studied in vivo and in vitro during postnatal development of piglets in order to examine whether in vitro metabolism approaches the in vivo situation. Experiments were performed in 1-day-, 8-day- and 60-day-old piglets. In vivo: 14C-SDZ was injected intravenously and urine and tissue samples collected after 3 hr. Urinary excretion data as well as data from liver and kidney tissue indicated a relatively high capacity for acetylation at birth, while the capacity for oxidation is low during the first week of life. At 60 days of age the acetylation and oxidation of SDZ is equal each accounting for about 20% of the amount excreted in urine. In vitro: Incubation of subcellular fractions of liver and kidney showed that acetylation of SDZ in liver reached maximum within 1 week. Oxidative activity was absent at 1 day, present at a low level at day 8, and at a high level at day 60. Neither acetylation nor oxidation of SDZ took place in kidney. The results show a close correlation between in vivo and in vitro results with respect to the developmental pattern seen in piglets during the postnatal period of life.

Short-term feeding study of the emulsifier Homodan MO in pigs

Abstract Groups of four female pigs were fed the emulsifier Homodan MO for 98 days at dietary levels of 0, 0·4, 2 and 10%. No significant effect was exercised on growth rate, food consumption, blood picture, liver and kidney function or organ weights and pathology, at any of the dietary levels administered.