Toxic Effects Of Ochratoxin Research Articles

Follow up long term preliminary studies on carcinogenic and toxic effects of ochratoxin A in rats and the putative protection of phenylalanine

Carcinogenic effects of ochratoxin A (OTA) on liver, kidneys, intestine, lung and eyes of Wistar rats exposed to 10 ppm or 5 ppm OTA in the diet and additionally supplemented or not with phenylalanine (PHE) were examined during 24-months experimental period. OTA was seen to provoke strong degenerative changes and slight pericapillary oedema in most internal organs, e.g. kidneys, liver, intestine, spleen and brain. Six of total nine neoplasms were identified as malignant and three as benign. Five of total six malignant neoplasms and two of total three benign neoplasms were seen in male rats. The pathological finding in rats after two weeks feeding with OTA-contaminated feed was dominated by degenerative changes in various internal organs, which were weaker in the group additionally supplemented with PHE. The protective effect of PHE was evident with respect to OTA-induced decrease of serum glucose and serum protein, but this protection was not singnificant with respect to serum enzymes activity. The number of neoplasms in PHE-supplemented group exposed to 10 ppm OTA was similar to that in the group exposed to twice lower feed levels of OTA alone, suggesting about a possible protective effect of PHE. The rats would not be able to serve as experimental model for humans with regard to OTA-induced tumorigenesis, because the target organ of OTA-toxicity in humans and pigs is mainly the kidney as opposed to the significant damages and carcinogenic effects seen in various organs in rats exposed to OTA.

Selected herbal feed additives showing protective effects against ochratoxin A toxicosis in broiler chicks

The protective effects of herbal feed additivesSilybum marianum, Withania somnifera andCentella asiatica against the toxic effects of ochratoxin A (OTA) were studied in 70 broiler chicks aged from 11 to 42 days. OTA was given with the feed at levels 5 mg/kg, whereasS. marianum,W. somnifera andC. asiatica were given at levels of 1,100, 4,000 and 4,600 mg/kg, respectively. All chicks were immunised at the age of 14 days against Newcastle disease. A protective effect of all studied herbal additives against the immunosuppressive effect of OTA and associated biochemical or pathomorphological changes was seen. The intensity of macroscopical and histopathological changes, the deviations in relative organs’ weight or body weight, the biochemical changes and the decrease of antibody titer were strongest in the OTA-exposed chicks without herbal supplementation; followed by chicks treated additionally withC. asiatica, whereas the same changes were significantly slighter or not seen in chicks additionally treated with the herbal additivesW. somnifera orS. marianum. The slight increase in the serum levels of uric acid and the enzyme activity of aspartate transaminase and alanine transaminase also supported the protective effects of both herbs on the kidneys and/or liver. The strong immunosuppressive effect of OTA on humoral immune response against Newcastle disease was completely prevented in the chicks taking the herbal additivesW. somnifera orS. marianum, which was supported by the higher relative weight of immunocompetent (lymphoid) organs in the same chicks. A hepatoprotective effect was found in OTA-exposed chicks treated additionally withW. somnifera andS. marianum, whereas a nephroprotective effect was only found in the chicks additionally treated withS. marianum as observed from the biochemical and pathomorphological findings. The same herbs could be used as a practical approach for safely utilising of OTA-contaminated feed.

Follow Up Long Term Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Rats and the Putative Protection of Phenylalanine

Follow Up Long Term Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Rats and the Putative Protection of Phenylalanine

Restorative effect of l-Dopa treatment against Ochratoxin A induced neurotoxicity

The toxic effects of Ochratoxin A (OTA), a fungal secondary metabolite of the genera Aspergillus and Penicillium with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) a Parkinson inducing drug were investigated to evaluate the neurotoxic effects exerted by OTA. OTA is known to contaminate food and feedstuff leading to a wide range of toxicity like nephrotoxicity, hepatotoxicity, and immunotoxicity. However, due to the dearth of available information on the possible mechanisms of OTA neurotoxicity and neurodegeneration the current study was undertaken. Hence, in this study, we examined the neurotoxic effects and the possible mechanism of action of neurodegeneration by OTA toxicity on mice brain by conducting a battery of behavioural studies and reviewing neurotransmitter levels and neuronal apoptotic pathways. Further, they were treated with l-Dopa, a precursor of dopamine (DA) to explore its ameliorative effects against OTA. The results of behavioural studies like gait analysis, spontaneous activity, cylinder test and pole test showed that OTA exhibits Parkinsonian physiognomies which were stabilized with l-Dopa treatment. Also, OTA toxicity showed insults on neurotransmitter levels and general brain function parameters that were normalized with l-Dopa treatment. The results of the present study suggest that OTA promotes neurodegeneration by targeting neuronal pathway leading to the development of Parkinson's diseases.

Toxic Effects of Ochratoxin A on Calcium Metabolism during Chick Embryo Developmentand in Hatched Chicks

The present study was carried out to study the effect of in-ovo ochratoxin A (OTA) injection in Highline layer eggs on calcium metabolism and blood biochemical parameters of embryos and after the hatch. At day 10 of embryonic development, one hundred and sixty-two fertile eggs were individually weighed and divided into two equal treatments. The first treatment (control) consisted of the individual injection of fertile eggs with 50 µL sodium carbonate. In the second treatment (OTA), fertile eggs were individually injected with 12.5 ng OTA dissolved in 50 µL sodium carbonate. On days 12, 14, and 16 of incubation and at the hatch, serum calcium and inorganic phosphorus concentrations were lower (p<0.05), while sodium, alkaline phosphatase and triiodothyronine concentrations were higher (p<0.05) in the OTA-injected eggs compared with the controls. Serum potassium concentration was not affected (p<0.05) by OTA treatment. Lower calcium and phosphorus levels were determined (p<0.05) in the allantoic fluid of OTA-injected eggs compared with the controls. On days 12, 14, and 16 of incubation and at the hatch, lower whole body and yolk calcium and phosphorus, but not sodium levels, were measured (p<0.05) in the OTA treatment compared with the controls. In conclusion, the injection of eggs with OTA reduced blood calcium and phosphorus levels, which were associated with reduced whole body and yolk content from these electrolytes. Therefore, ochratoxin A had a negative effect on calcium metabolism.

The study of the Toxic Effects of Ochratoxin A the purified from fungus Aspergillus niger in vivo of White rats and Evaluating the Ability of the Bio-lotion Floramil in the Reduction of Its Toxicity.

The study of the Toxic Effects of Ochratoxin A the purified from fungus Aspergillus niger in vivo of White rats and Evaluating the Ability of the Bio-lotion Floramil in the Reduction of Its Toxicity.

Pro-inflammatory and toxic effects of ochratoxin and ochratoxin α in human neutrophils

Pro-inflammatory and toxic effects of ochratoxin and ochratoxin α in human neutrophils

Studies on carcinogenic and toxic effects of ochratoxin A in chicks.

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver.

Influence of Vitamins E and C on the Toxic Effects of Ochratoxin A and T-2 Toxin in Chicks

The objective of this study was to determine whether two antioxidant vitamins, vitamins E and C, were able to counteract the production of lipid peroxides and the corresponding toxic signs of two important but diverse mycotoxins, T-2 toxin and ochratoxin A (OA). Experiment 1 was designed in a 3 × 3 factorial arrangement using three doses of vitamin E (dl-α-tocopheryl acetate) in the diet of Leghorn cockerels (required level according to NRC, l0×, and l00× requirements) and three toxin treatments [no toxin (Diets 1, 2, and 3), 4 mg T-2/kg of diet (Diets 4, 5, and 6), and 2.5 mg OA/kg of diet (Diets 7, 8, and 9)]. The experimental design for Experiment 2 was the same as for Experiment 1 except that Vitamin C (0, 200, and 1,000 mg/kg of diet) was used in place of vitamin E and the concentration of T-2 in Diets 4, 5, and 6 was increased to 5 mg/kg of diet. Six replicates were used per treatment with four birds per replicate. In both experiments, OA and T-2 decreased the performance of the chicks significantly. The concentration of uric acid in the plasma increased (P < 0.001) when OA was added to the diet, whereas the supplementation of the diet with vitamin E (l00× the requirement) partially counteracted this effect (P = 0.07). The presence of T-2, and especially OA, in the diet decreased the concentration of α-tocopherol in the liver (P < 0.001). Consistent with these findings were increased values of malondialdehyde (MDA) in the liver due to OA. In Experiment 1, vitamin E supplementation partially ameliorated the prooxidative effects of OA by decreasing the concentrations of MDA (P < 0.05). These data suggest that lipid peroxides are formed in vivo by T-2 and especially by OA and that these effects can be partially counteracted by an antioxidant such as vitamin E but not by vitamin C.

Aspartame as a Preventive Agent of Chronic Toxic Effects of Ochratoxin a in Experimental Animals

AbstractOchratoxin A (OTA) is a mycotoxin produced by ubiquitous Aspergilli, mainly by Aspergillus ochraceus and also by Penicillium verrucosum. It is found all over the world in feed and Human food and blood as well as in animal blood and tissues.The most threatening effects of OTA are nephrotoxicity and carcinogenicity, since this mycotoxin is nephrotoxic to all animal species studied so far and is increasingly involved in the Balkan Endemic Nephropathy (BEN) a human chronic interstitial nephropathy which is most of the time associated to urinary tract tumours.Many data are available on the different mechanisms whereby OTA is absorbed, transported, distributed, metabolised, accumulated and/or eliminated in vivo. Its molecular mode of action in vivo and in vitro in the inhibition of total protein synthesis and of a specific protein such as renal phosphoenolpyruvate carboxykinase (PEPCK) are also well documented.There are evidence of the implication of oxidative pathways in the OTA-induced cellular damage...

Prevention of toxic effects of ochratoxin A, a natural contaminant of mouldy food and feed: effects of A 19 (structural analogue of phenylalanine), on the nephrotoxicity in rats and on the inhibition of protein synthesis in Vero cells

Prevention of toxic effects of ochratoxin A, a natural contaminant of mouldy food and feed: effects of A 19 (structural analogue of phenylalanine), on the nephrotoxicity in rats and on the inhibition of protein synthesis in Vero cells

Impact of L-Phenylalanine Supplementation on the Performance of Three-Week-Old Broilers Fed Diets Containing Ochratoxin A.: 2. Effects on Hematology and Clinical Chemistry

Phenylalanine was evaluated for its ability to protect broiler chickens from the toxic effects of ochratoxin A (OA). A completely randomized 2-by-3 factorial design was utilized consisting of 0, .8, and 2.4% supplemental L-phenylalanine (Phe) and of 0 and 4 mg of OA per kg of diet. The basal diet contained 14% protein. Broilers were raised in battery brooders to 3 wk of age, when blood was collected and various hematological parameters were determined. The health status of the broilers was evaluated by assaying serum for various enzyme activities and metabolites using an automated, clinical chemistry analyzer.Adding OA to the broiler diets resulted in an increased concentration of serum hemoglobin as well as increased activity for cholinesterase and gamma glutamyl transferase but in decreased activity for aspartate amino transferase, lactate dehydrogenase, and alkaline-phosphatase activity as well as decreased concentrations of total triglyceride and of inorganic phosphorus. Supplemental Phe decreased the concentrations of hemoglobin and serum glucose.The regression slopes for Phe at 4 mg of OA per kg of diet were significant for uric acid, creatinine, total protein, albumin, and cholesterol suggesting that supplemental Phe improved the health status of the broilers fed diets containing OA with respect to these parameters.

Toxic effects of ochratoxin A and citrinin, alone and in combination, on chicken embryos.

The embryotoxic potential of ochratoxin A and citrinin was studied after administering, either subgerminally or intraamniotically, single mounting doses of the mycotoxins to chicken embryos on days 2, 3, and 4. The beginning of the embryotoxicity dose range was found to be between 0.01 to 0.05 microgram for ochratoxin A and 1 to 10 micrograms for citrinin. The maximum response to both mycotoxins occurred after administration on day 3. In addition to significant growth retardation of fetuses, exencephaly, microphthalmia, cleft beak, reduction deformities of the limbs, and abdominal wall and ventricular septal defects were encountered on day 8 of incubation. When 4 micrograms of citrinin was constantly added to ochratoxin A administered in the dose range of 0.03 to 0.5 microgram, a strictly additive effect was seen. It may be supposed that citrinin produced together with ochratoxin A in some strains of Penicillium viridicatum Westling does not potentiate the clear-cut embryotoxic action of the latter mycotoxin.

Teratogenic and toxic effects of ochratoxin A in rats

The mycotoxin ochratoxin A, is a teratogen as well as a potent nephrotoxin. Crystalline ochratoxin A was dissolved in 0.1 n NaHCO 3 and given daily by gastric intubation to rats on Days 6–15 of gestation. There were 10 rats per group and the dose levels tested were 0.25, 0.50, 0.75, 1, 2, 4, and 8 mg/kg. Acute ochratoxicosis, characterized mainly by signs of renal failure, occurred in dams given 4 or 8 mg/kg. Several dams died and the litters were resorbed in all dams given the larger doses. Signs of toxicosis were not observed in dams given 1 or 2 mg/kg, but their litters were also resorbed. There was no sign of toxicosis in dams given 0.25, 0.50, or 0.75 mg/kg. However, at Day 20, there was an increased incidence of fetal resorption in dams given 0.75 mg/kg. All fetuses taken on gestation Day 20 from dams given 0.25, 0.50 or 0.75 mg/kg weighed significantly less than control fetuses, and fetuses from dams given 0.75 or 1.0 mg/kg were stunted. Many had open eyes, deformed snouts, and other major alterations including wavy ribs and agenesis of vertebrae. At the lower doses, ochratoxin A was teratogenic, but at the higher doses it was embryocidal.