Ochratoxin A Toxicosis in Swine

Szczech, George M.; Carlton, William W.; Tuite, J.; Caldwell, R. W.

doi:10.1177/030098587301000408

Cited by 91 publications

(31 citation statements)

References 26 publications

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“…These results mean that a moderate level (approximately 0.4 mg/kg) of OTA in the feed does not result in clinical signs of toxicity as also reported by Szczech et al (1973), but it may cause a certain decrease in the production traits which was previously proposed only at much higher levels of OTA (> 0.8 mg/kg feed) fed for longer periods (one year) in growing-finishing pigs (Stoev et al, 2002).…”

Section: Discussionsupporting

confidence: 77%

“…Ochratoxin is a fungal nephrotoxin produced by Aspergillus and Penicillium moulds (Steyn, 1995). Clinical signs of ochratoxicosis at levels of 1 mg/kg feed or higher are polydipsia, polyuria, reduced growth and lowered feed efficiency, while lower amounts of the toxin cause no clinical symptoms, only the pale, firm appearance of the kidney at slaughter (Szczech et al, 1973) as a consequence of nephropathy (Glávits et al, 1993). The toxicity of ochratoxin is related to its binding to specific receptors for organic ion transporters of the renal tubular cells (Marquardt and Frohlich, 1992).…”

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confidence: 99%

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Effects of ochratoxin a on some production traits, lipid peroxide and glutathione redox status of weaned piglets

Balogh

Hausenblasz

Kovács-Weber

et al. 2007

Acta Veterinaria Hungarica

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The effect of feeding ochratoxin A (OTA) contaminated diet (379.6 and 338.1 µg/kg in starter and grower diets) on production traits, lipid peroxidation and some parameters of the glutathione redox system were investigated in weaned piglets over a seven-week period. Feed intake and feed conversion ratio (FCR) did not differ significantly, but in the first phase (0-28 days) the daily weight gain was significantly lower in the piglets fed the OTA-contaminated diet. Lipid peroxidation, as measured by the amount of malondialdehyde, glutathione content and glutathione peroxidase activity, did not change significantly in the blood plasma and red blood cell haemolysate in the OTA-loaded group, while malondialdehyde content increased significantly in the liver and markedly but not significantly in the kidney of piglets fed OTA-contaminated feed. Glutathione content did not differ significantly in the studied organs of the two groups while glutathione peroxidase activity of the OTA-loaded animals was significantly lower both in the liver and in the kidney. The results suggest that the use of feedstuffs contaminated with low levels of OTA for seven weeks did not cause marked differences in the production traits or in lipid peroxidation and amount or activity of the glutathione redox system in the blood plasma, red blood cells and kidney, while significant changes occurred in the liver homogenate.

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Effects of ochratoxin a on some production traits, lipid peroxide and glutathione redox status of weaned piglets

Balogh

Hausenblasz

Kovács-Weber

et al. 2007

Acta Veterinaria Hungarica

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“…1965 8;Purchase and Theron, 1968;Peckham et aI., 1971 andSzczech et al, 1973). The main pathological changes associated with aTA toxicity arc primarily damage 10 the kidney and to a lesser extent damage to the liver (Harwig, 1974 andKrogh.…”

Section: Toxicitymentioning

confidence: 99%

Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A

Omar

Gelboin

Rahimtula

1996

Biochemical Pharmacology

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The role of cytochrome P-450 in me stimulation of lipid peroxidation induccd by thc mycotoxin ochratoxin A (OTA) has been investigated. Purified cytochrome P-450 (liB I) could effectively replace EDTA in stimulating lipid pefOxidation in a reconstituted system l'Onsisling of phospholipid vesicles, NADPH-cYlochrome P-450rcduc!ase, FeJ+, EDTA and NADPll, suggesting that it could mediate the transfer of electrons from NADPH to foc3,. Microsomcs isolated from liven of cobalt protoporphyrin IX-treated rllts (in which cytochrome P-450 Wll" depletedj underwent OTA-dependent lipid peroxidation much more slowly tlmn control microsomes.The role of cytochrome P-450 in OTA met.1bolism was also investigated. To dClermine which cytochrome P·450 isoforms are involved in the metabolism ofOTA, we used different cytochrome P-450 inducers to induce the major isofonns of cytochrome 1'-450 in lhe rm liver.Microsomes from these livers were used to investigate their effect on OTA metabolism.Pretreatment ofmts with pregnenolone -16c(·carbonitrile (peN), phenobarbit.ll (PB), 3-ll1cthyl cholanthrene (3MC), and isosafrole (ISF) greatly induced 4(R)-4-0H-OTA fonmllion; 4(5)-4-011-OTA fonnation was also induced after pretreatment with PB, PCN, 3MC and ISr:. INII pretreaunem primarily induced me 4(5) isomer formation, The fonnation of the 4(R) .md 4 (5) isomeri showed significant differences with respect to pH optima, effect of antioKidants ami iron chelators, The 4(R) isomer fonnation showed a pH optimum of 6.0 using microsornes from rJIs treated with 3MC and ISF, and 6.5 using mierosomes from rats treated with PI] :tnd peN and Wi!S not inhibited by antioxidants or iron chelators. In contmst, both the 4(5) isomer fonmllion and lipid pcroxidation showed a pH optimum of 7.0 -7,5 and both activities were highly sensitive to inhibition by antioxidants and iron ehelators. Lipid peroxides were no: involved in the 4(5) isomer fonnation since addition of linoleic acid hydroperoxidc to microsomcs did not give rise 10 the 4(5) isomer, Cytochrome P-450 appeared to be essenlial since other hemoprolcins such as horseradish peroxidase and hemoglobin were ineffective in metabolizing OTA. Microsomes from rats pretreated with Co-protoporphyrin IX resulted in no metabolil,rn of ochratoxin A. 7-Ethoxy-and 7-pentoxyresorufin assays showed specificity towards cytochromes P-450 induced by 3MC (fA I/lA2) and PB (IIBI) respectively. Also, metyrapone (inhibitor of cytochrome P·450 IIBt) preferentially inhibited OTA mel1bolism by microsomes from rats treated with PB, and I(-naphthoflavone (inhibitor of cytochrome P-450 IAI/lA2) preferentially inhibited OTA metabolism by microwmes from 3MC and ISF treated rats_ Monoclonal antibodies (MAbs) 1-7-1 (against P-450 lA 1/lA2) and 2-66-3 (against P-450 liB I) showed preferential inhibition ofOTA metabolism by microsomes from 3MC and PB treated rats respectively.Excretion of renal enzymes in urine is a sensitive non-invasive index of renal dam:lge.Therefore. we examined the effect of cytochrome P-450 induction on the...

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“…Soon after the first description o f OTA, several groups started to investigate its possible toxic actions in different animal models [6][7][8]. The purpose o f those studies was to determine the main target o f the toxin within the organism.…”

Section: Introductionmentioning

confidence: 99%

Renal Toxicodynamics of Ochratoxin A: A Pathophysiological Approach

Gekle

Silbernagl²

1996

Kidney Blood Press Res

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Ochratoxin A (OTA) is a secondary fungal metabolite that has been detected in a variety of animal chows, human food and in up to 80% of human blood samples of several Western countries. Its main target is the kidney. OTA is the causing agent of Danish porcine nephropathy and increases the incidence of renal carcinomas and adenomas in rats. Pathophysiological studies revealed that OTA acts on different sites along the nephron. Acute OTA exposure leads to an impairment of postproximal nephron function, predominantly of the collecting duct, resulting in altered electrolyte and titratable acid excretion. The underlying mechanism is most probably a blockade of anion conductance in the plasma membrane at nanomolar concentrations of OTA with subsequent disturbance of cellular acid-base homeostasis as shown in cultured kidney cells. Disturbance of cellular pH homeostasis is probably also involved in OTA-induced transformation of cultured kidney cells. Chronic OTA exposure leads to an additional reduction in the urine concentrating ability. Renal hemodynamics and the secretory function of the proximal tubule are affected by OTA after prolonged but not by acute exposure. OTA increases resistance in the vas efferens with a subsequent decrease in renal blood flow and glomerular filtration rate. Proximal tubular cells respond to OTA with a dramatic reduction in the secretory capacity for organic anions. The resorptive capacity for small molecules like amino acids is affected only to a minor extent, whereas endocytic uptake of albumin is clearly reduced. Furthermore, OTA has a mitogenic potential on rat proximal tubular cells in primary culture if applied in nanomolar concentrations but inhibits cell growth at micromolar concentrations. According to the above-described effects OTA exerts a complex action on renal function depending on the dose and time of exposure. The high incidence of OTA in human food and blood samples taken together with its diverse effects on renal function should attract further attention to this mycotoxin as a possible candidate for renal malfunction of unknown origin in humans.

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Ochratoxin A Toxicosis in Swine

Cited by 91 publications

References 26 publications

Effects of ochratoxin a on some production traits, lipid peroxide and glutathione redox status of weaned piglets

Effects of ochratoxin a on some production traits, lipid peroxide and glutathione redox status of weaned piglets

Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A

Renal Toxicodynamics of Ochratoxin A: A Pathophysiological Approach

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