Effect of Ochratoxin A and Aristolochic Acid on a Porcine Kidney Cell Line

Authors

  • Daniela Eliza Marin Research and Development Institute for Biology and Animal Nutrition, Balotesti, Calea Bucuresti no 1, Ilfov, Romania
  • Gina C. Pistol Research and Development Institute for Biology and Animal Nutrition, Balotesti, Calea Bucuresti no 1, Ilfov, Romania
  • Ionelia Taranu Research and Development Institute for Biology and Animal Nutrition, Balotesti, Calea Bucuresti no 1, Ilfov, Romania

Keywords:

aristolochic acid, cytokines, LLC-PK, ochratoxin A.

Abstract

The Balkan endemic nephropathy (BEN) is an irreversible, chronic, tubulo-interstitial nephropathy described so far in several rural regions from the Balkan with an unknown aetiology. Both ochratoxin A (OTA) and aristolochic acid (AA) are considered responsible for BEN. This paper performed a comparison between the toxic effect of OTA and AA using a kidney cell line LLC-PK. OTA and AA decreased cell viability in a dose dependent manner. The dose dependent effect was observed for both toxins, the doses higher than 5mg/mL inducing a significant inhibition of viability (P<0.05) in AA and OTA treated cells, when compared with control. For doses higher than 50mg/mL, the toxicity of AA was higher than the OTA cytotoxicity. A slight decrease of IL-8 was observed after 6h, for OTA, while AA slightly increases the IL-8 synthesis. After 24h, IL-8 synthesis was decreased by both toxins, AA having a more pronounced effect than OTA. IL-10 synthesis was not affected by the treatment of both toxins. In conclusion, both OTA and AA negatively affect LLC-PK cells viability and capacity to synthesize IL-8, with AA being more toxic than OTA for the highest concentrations used in this study.

References

Bennett, J. W., Klich, M., Mycotoxins. Clinical Microbiology Review, 2003, 16, 497–516.

Blesa, J., Soriano, J. M., Molto, J. C., Manes, J., Factors affecting the presence of ochratoxin A in wines. Crit Rev Food Sci Nutr., 2006, 46, 473–478.

Stefanovic, V., Toncheva, D., Atanasova, S., Polenakovic, M., Etiology of Balkan endemic nephropathy and associated urothelial cancer, Am J Nephrol., 2006, 26, 1-11.

Marin, D., Motiu, M., Taranu, I., Effect of Ochratoxin A and Aristolochic Acid on an Epithelial Intestinal Cell Line, Bulletin UASVM Animal Science and Biotechnologies, 2014, 71(2).

Schaaf, G. J., Nijmeijer, S. M., Maas, R. F., Roestenberg, P., de Groene, E. M., Fink-Gremmels, J., The role of oxidative stress in the ochratoxin A-mediated toxicity in proximal tubular cells, Biochim Biophys Acta. 2002, 1588, 149-158.

Petrik, J., Mali, A., Bari, K., Rumora, L., Kõszegi, T, Pepeljnjak, S, Zanic-Grubisic, T., Cepelak I., Ochratoxin A Induces Apoptotic and Necrotic Renal Cell Death, Croatica Chemica Acta, 2005, 78, 447-453.

Gao, R., Zheng, F., Liu, Y., Zheng, D., Li, X., Bo, Y., Liu, Y., Aristolochic acid I-induced apoptosis in LLC-PK1 cells and amelioration of the apoptotic damage by calcium antagonist, Chin Med J., 2000, 113, 418-424.

Stachurska, A., Kozakowska, M., Jozkowicz, A., Dulak, J., Lobod,a A., .Aristolochic acid I and ochratoxin A differentially regulate VEGF expression in porcine kidney epithelial cells--the involvement of SP-1 and HIFs transcription factors, Toxicol Lett., 2011, 204, 118-126.

Peveri, P., Walz, A., Dewald, B., Baggiolini, M., A novel neutrophil-activating factor produced by human mononuclear phagocytes, J Exp Med,1988, 167, 1547–1559.

Thelen, M., Peveri, P., Kernen, P., von Tscharner, V., Wa, L. Z., A., Baggiolini I., M., Mechanism of neutrophil activation by NAF, a novel monocyte-derived peptide agonist, Faseb J., 1988, 2, 2702–2706.

Iyer, S. S., Cheng. G.. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease, Crit Rev Immunol., 2012, 32, 23-63.

Klahr, S., Morrissey, J., Progression of chronic renal disease, Am J Kidney Dis, 2003, 41, S3–7.

Armstrong, L., Jordan, N., Millar, A., Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes., Thorax, 1996, 51, 143–9.

Odhav, B., Adam, J. K., Bhoola, K. D., Modulating effects of fumonisin B1 and ochratoxin A on leukocytes and messenger cytokines of the human immune system, Int Immunopharmacol, 2008, 8, 799–809.

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Published

2023-09-12