Evaluation of the Expression of RCC and KIM-1 Biomarkers in Nephrotoxicity of Rabbits Treated with Ochratoxins A
Main Article Content
Keywords
Ochratoxin A (OTA), Nephrotoxicity, RCC, KIM-1, Biomarkers
Abstract
Mycotoxin known as ochratoxin A (OTA) is generated by a number of fungi, including Aspergillus ochraceus, Aspergillus carbonarius, Aspergillus niger, and Penicillium verrucosum. OTA causes kidney tumors and nephrotoxicity in humans and a number of other animal species. This study was conducted to determine the effect of OTA in the kidney of New Zealand White rabbits and the role of RCC and KIM-1 biomarkers in kidney toxicity induced by OTA. Histopathological study showed various pathological effects of rabbit’s kidneys treated with 0.5 mg/kg (body weight intraperitoneally) with OTA in comparison with control animals. RCC and KIM-1 were used as biomarkers for the immunohistochemical study, results showed that there were no expressions in control animals (score =0), while the expressions of RCC and KIM-1 in animals kidney treated with 0.5 mg/kg (body weight intraperitoneally) of OTA were strong (score =3) and moderate (score =2) respectively.
References
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29. Krogh, P. Role of ochratoxin in disease causation. Food and Chemical Toxicology 1992; 30 ( 3): 213-224.
30. Joseph, V.B. Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney injury. Journal of Clinical and Laboratory Investigation 2008 ; 241:78-83.
31. Bonventre, J.V. Kidney injury molecule-1 (KIM-1): A specific and sensitive biomarker of kidney injury. Scandinavian Journal of Clinical and Laboratory Investigation 2008; 241: 78–83.
32. Hyun, J. L., Min, C. P., Hye, S.Shin., Dojin, R and Kwang-Won, L. Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of ochratoxin A-induced oxidative stress in kidney cells. Food and Chemical Toxicology 2018; 122: 59-68.
33. Liye, Z., Tao, Y., Xiaozhe, Q., Jing, G., Kunlun, H, Xiaoyun, H., Haoshu, L and Wentao, X. Limited Link between Oxidative Stress and Ochratoxin A-Induced Renal Injury in an Acute Toxicity Rat Model. Toxins (Basel) 2016; 14;8(12):373
34. Xiaozhe,Q.,Tao,Y.,Liye,Z.,Jing,G.,Xiaoyun,H.,Kunlun,H.,Yunbo,L and Wentao,X. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses. Toxicology and Applied Pharmacology 2014; 280 (3): 543-549.
35. Waikar, S.S and Bonventre, J. V. Biomarkers for the diagnosis of acute kidney injury, Current Opinion in Nephrology and Hypertension 2007; 16: 557-564.
36. Vaidya, V. S., Ferguson, M. A and Bonventre, J. V. Biomarkers of acute kidney injury. Annual Review of Pharmacology and Toxicology 2008; 48: 463-493.
2. Atumo,S. A Review of Ochratoxin A Occurrence, Condition for the Formation and Analytical Methods. International Journal of Agriculture Science Food Technology 2020; 6(2): 180-185.
3. Rosa, V., Antonella A., Carlo, G and Francesco,P. Determination of Ochratoxin A in green coffee beans by solid phase micro extraction and liquid chromatography with fluorescence detection. Journal of Chromatography A 2008; 1187: 145-150.
4. Stoev, D and Vet, H. (2010). Toxicol. Journal of food science 6: 40-46.
5. IARC. Monography on the evaluation of carcinogenic risks to humans some naturally occurring substance. Journal of International agency for research on cancer 1993; 56: 489-496.
6. Barnett, L.M.A., Cummings, B.S. Nephrotoxicity and renal pathophysiology: A contemporary perspective. Toxicology Science 2018; 164:379–390.
7. Adam, A.A.M., Tabana, Y.M., Musa, K.B and Sandai, D.A. Effects of different mycotoxins on humans, cell genome and their involvement in cancer (Review) Oncology Report 2017; 37:1321–1336.
8. Curti, B., Jana, BRP., Javeed, M., Makhoul, I., Sachdeva, K., Hu, W., Perry, M and Talavera, F. Harris, JE (ed.). "Renal Cell Carcinoma". Medscape Reference. WebMD. Archived from the original on 7 March 2014. Retrieved 7 March 2014.
9. EAU Guidelines: Renal Cell Carcinoma". Retrieved 24 April 2020.
10. Eva, R., Dana, H., Blumbach, K., Wolfgang, D and Angela M. Evaluation of Putative Biomarkers of Nephrotoxicity after Exposure to Ochratoxin A In Vivo and In Vitro. Journal of Toxicological Sciences 2008; 103 ( 2): 371-371.
11. Takaharu L., Cheng, C., Soon, A., James, L, and Joseph V. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. American Journal of Physiology Renal Physiology 2003; 286: 552-563.
12. Xinghua, S.,Lei T., Weijia Xu., Zhen Z., Chunlin W., Chaojun Q., Zhaohui N and Shan M. Diagnostic Value of Urinary Kidney Injury Molecule 1 for Acute Kidney Injury: A Meta-Analysis. National center of Biotechnology Information2014; 9(1): e84131.
13. Jessica,G, S., Covadonga,V and Belen, P. Mycotoxins | Toxicology. Reference Module in Food Science 2019.
14. Luna, L.G. Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology. 3 rd., New York, McGraw-Hill Book Company, 38- 76. 222-223. 1968.
15. Davidson, B., Vintman, L., Zcharia, E., Bedrossian, C., Berner, A., Ilan, N., Vlodavsky, I., Reich, R and Nielsen, S. Heparanase and basic fibroblast growth factor are co-expressed in malignant mesothelioma Clinical Expression. National Library of Medicine 2004; 21: 469-476.
16. Petzinger, E and Ziegler, K. Ochratoxin A from a toxicological persective. Journal of Veterinary Pharmacology Therapeutics 2000; 23: 91-98.
17. Hult, K., Plestina, R., Habazin-Novak, V., Radic, B and Ceovic, S. Ochratoxin A in human blood and Balkan endemic nephropathy. Archives of Toxicology 1982; 51: 313-321.
18. Huff, J.E. Carcinogenicity of ochratoxin A in experimental animals. IARC Scientific Publications1991; 115: 229 -44.
19. Bahnemann, E., Kerling, H.P., Ensminger, S., Schwerdt, G., Silbernagl, S and Gekle, M. Renal transepithelial secretion of ochratoxin A in the non-ltering toad kidney. Toxicology 1997;120: 11-17.
20. Boorman, G.A and McDonald, M.R. Imoto S, Persing R. Renal lesions induced by ochratoxin A exposure in the F344 rat. Journal of Toxicologic Pathology1992; 20: 236 - 45.
21. Aydin, G., Ozelik, E and Soyoz, M. Histopathologic changes in liver and renal tissues induced by Ochratoxin A and melatonin in rats. Human and Experimental Toxicology 2003; 22: 383 -391.
22. Doaa, H., Assar, Samah , A., Moshira A., Zizy I., Mustafa S., Amera ., Mona, N., Norah, A. and Mohammed A. Aspergillus awamori attenuates ochratoxin A-induced renal and cardiac injuries in rabbits by activating the Nrf2/HO-1 signaling pathway and downregulating IL1β, TNFα, and iNOS gene expressions. Journal of Environmental Science and Pollution Research 2002; 29:69798- 69817.
23. Grosse, P., Chekir-Ghedira, L and Hue, A. Retinol, ascorbic acid and alpha-tocopherol prevent DNA adduct formation in mice treated with the mycotoxins ochratoxin A and zearalenone. Journal of Cancer Letters 1997; 114: 225 - 229.
24. Gong, L., Zhu, H., Li, T., Ming, G., Duan, X.,Wang, J and Jiang, Y. Molecular signatures of cytotoxic effects in human embryonic kidney 293cells treated with single and mixture of ochratoxin A and citrinin. Journal of Food and Chemical Toxicology 2019; 123: 374–384.
25. Ozcan, Z., Gul, G and Yaman, I. Ochratoxin A activates opposing c-MET/PI3K/Akt and MAPK/ERK 1-2 pathways in human proximal tubule HK-2 cells. Journal of Archives of Toxicology 2015; 89: 1313–1327.
26. Kuroda, N., Sugawara, E., Kusano, H., Yuba, Y., Yorita, K and Takeuchi, K. A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects. Polish Journal of Pathology 2018; 69(2):109-113.
27. Lopez-Beltran, A.L., Escudero, A.O., Cavazzana, L.G., Spagnoli, L.G and Vicioso-Recio, L. Sarcomatoid transitional cell carcinoma of the renal pelvis. A report of five cases with clinical, pathological, immunohistochemical and DNA ploidy analysis. Pathology - Research and Practice 1996; 192: 218–1224.
28. Bendele, A.M., Carlton, W.M., Krogh, P and Lillehoj, E.B. Ochratoxin A carcinogenesis in the (C57BL/6J x C3)F1 mouse. J. Natl. Cancer Inst 1985;75, 733–742.
29. Krogh, P. Role of ochratoxin in disease causation. Food and Chemical Toxicology 1992; 30 ( 3): 213-224.
30. Joseph, V.B. Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney injury. Journal of Clinical and Laboratory Investigation 2008 ; 241:78-83.
31. Bonventre, J.V. Kidney injury molecule-1 (KIM-1): A specific and sensitive biomarker of kidney injury. Scandinavian Journal of Clinical and Laboratory Investigation 2008; 241: 78–83.
32. Hyun, J. L., Min, C. P., Hye, S.Shin., Dojin, R and Kwang-Won, L. Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of ochratoxin A-induced oxidative stress in kidney cells. Food and Chemical Toxicology 2018; 122: 59-68.
33. Liye, Z., Tao, Y., Xiaozhe, Q., Jing, G., Kunlun, H, Xiaoyun, H., Haoshu, L and Wentao, X. Limited Link between Oxidative Stress and Ochratoxin A-Induced Renal Injury in an Acute Toxicity Rat Model. Toxins (Basel) 2016; 14;8(12):373
34. Xiaozhe,Q.,Tao,Y.,Liye,Z.,Jing,G.,Xiaoyun,H.,Kunlun,H.,Yunbo,L and Wentao,X. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses. Toxicology and Applied Pharmacology 2014; 280 (3): 543-549.
35. Waikar, S.S and Bonventre, J. V. Biomarkers for the diagnosis of acute kidney injury, Current Opinion in Nephrology and Hypertension 2007; 16: 557-564.
36. Vaidya, V. S., Ferguson, M. A and Bonventre, J. V. Biomarkers of acute kidney injury. Annual Review of Pharmacology and Toxicology 2008; 48: 463-493.
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Published
Mar 7, 2023
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Fadia Falah Hassan, Rana Alaa Al-Aamery, Sarah Nori Hussein, & Tareq Hashim. (2023). Evaluation of the Expression of RCC and KIM-1 Biomarkers in Nephrotoxicity of Rabbits Treated with Ochratoxins A. Journal of Population Therapeutics and Clinical Pharmacology, 30(2), 337–343. https://doi.org/10.47750/jptcp.2023.1116
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