An integrated view of aristolochic acid nephropathy: Update of the literature

International Journal of Molecular Sciences

Volumn 18, Issue 2, 2017, Pages

  Jadot, Inès ^a   Declèves, Anne Emilie ^b   Nortier, Joëlle ^c   Caron, Nathalie ^a  

^a University of Namur   (Belgium)

^b UNIVERSITY OF MONS   (Belgium)

^c ERASME HOSPITAL   (Belgium)

Author keywords

Aristolochic acids; Balkan endemic nephropathy; Herbal remedies; Renal interstitial fibrosis; Urothelial carcinoma

Indexed keywords

ARISTOLOCHIC ACID; CARBOXYLIC ACID DERIVATIVE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; MEMBRANE METALLOENDOPEPTIDASE; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 4; ORGANIC ANION TRANSPORTER; TRANSFORMING GROWTH FACTOR BETA; HERBACEOUS AGENT;

APOPTOSIS; CARCINOGENIC ACTIVITY; ENVIRONMENTAL EXPOSURE; FANCONI RENOTUBULAR SYNDROME; GENETIC POLYMORPHISM; GLOMERULUS FILTRATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; INDUCED MUTATION; INFLAMMATION; ION TRAP MASS SPECTROMETRY; KIDNEY BIOPSY; KIDNEY DISEASE; KIDNEY FIBROSIS; KIDNEY FUNCTION; KIDNEY TRANSPLANTATION; NEPHROTOXICITY; NONHUMAN; OXIDATIVE STRESS; REVIEW; STEPHANIA TETRANDRA; TRANSITIONAL CELL CARCINOMA; TUMOR SUPPRESSOR GENE; ANIMAL; BALKAN NEPHROPATHY; BIOPSY; CELL TRANSFORMATION; CHEMICALLY INDUCED; CHEMISTRY; FIBROSIS; KIDNEY NEOPLASMS; METABOLISM; NEPHRITIS, INTERSTITIAL;

ANIMALS; ARISTOLOCHIC ACIDS; BALKAN NEPHROPATHY; BIOPSY; CELL TRANSFORMATION, NEOPLASTIC; DRUGS, CHINESE HERBAL; FIBROSIS; HUMANS; KIDNEY NEOPLASMS; NEPHRITIS, INTERSTITIAL; OXIDATIVE STRESS;

EID: 85011085105     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms18020297     Document Type: Review

References (150)

1. Vanherweghem, J.L.; Depierreux, M.; Tielemans, C.; Abramowicz, D.; Dratwa, M.; Jadoul, M.; Richard, C.; Vandervelde, D.; Verbeelen, D.; Vanhaelen-Fastre, R. Rapidly progressive interstitial renal fibrosis in young women: Association with slimming regimen including Chinese herbs. Lancet 1993, 341, 387–391.
2. Depierreux, M.; Van Damme, B.; Vanden Houte, K.; Vanherweghem, J.L. Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs. Am. J. Kidney Dis. 1994, 24, 172–180.
3. Vanhaelen, M.; Vanhaelen-Fastre, R.; But, P.; Vanherweghem, J.-L. Identification of aristolochic acid in Chinese herbs. Lancet 1994, 343, 174.
4. Cosyns, J.; Jadoul, M.; Squifflet, J.-P.; Van Cangh, P.; van Ypersele de Strihou, C. Urothelial malignancy in nephropathy due to Chinese herbs. Lancet 1994, 344, 188.
5. Nortier, J.L.; Martinez Muniz, M.-C.; Schmeiser, H.H.; Arlt, V.M.; Bieler, C.A.; Petein, M.; Depierreux, M.F.; de Pauw, L.; Abramowicz, D.; Vereerstraeten, P.; et al. Urothelial carcinoma associated with the use of a Chinese herb. N. Engl. J. Med. 2000, 342, 1686–1692.
6. World Health Organization. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. In IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC Press: Lyon, France, 2002; Volume 82.
7. Debelle, F.D.; Vanherweghem, J.-L.; Nortier, J.L. Aristolochic acid nephropathy: A worldwide problem. Kidney Int. 2008, 74, 158–169.
8. Chen, C.-H.; Dickman, K.G.; Moriya, M.; Zavadil, J.; Sidorenko, V.S.; Edwards, K.L.; Gnatenko, D.V.; Wu, L.; Turesky, R.J.; Wu, X.-R.; et al. Aristolochic acid-associated urothelial cancer in Taiwan. Proc. Natl. Acad. Sci. USA 2012, 109, 8241–8246.
9. Hsieh, S.-C.; Lin, I.-H.; Tseng, W.-L.; Lee, C.-H.; Wang, J.-D. Prescription profile of potentially aristolochic acid containing Chinese herbal products: An analysis of National Health Insurance data in Taiwan between 1997 and 2003. Chin. Med. 2008, 3, 13.
10. Lai, M.N.; Lai, J.N.; Chen, P.C.; Tseng, W.L.; Chen, Y.Y.; Hwang, J.S.; Wang, J.D. Increased risks of chronic kidney disease associated with prescribed Chinese herbal products suspected to contain aristolochic acid. Nephrology 2009, 14, 227–234.
11. Ng, Y.Y.; Yu, S.; Chen, T.W.; Wu, S.C.; Yang, A.H.; Yang, W.C. Interstitial renal fibrosis in a young woman: Association with a Chinese preparation given for irregular menses. Nephrol. Dial. Transplant. 1998, 13, 2115–2117.
12. Cosyns, J.; Jadoul, M.; Squifflet, J.; Plaen, J.; Ferluga, D.; van Ypersele de Strihou, C. Chinese herbs nephropathy: A clue to Balkan endemic nephropathy? Kidney Int. 1994, 45, 1680–1688.
13. Arlt, V.M.; Ferluga, D.; Stiborova, M.; Pfohl-Leszkowicz, A.; Vukelic, M.; Ceovic, S.; Schmeiser, H.H.; Cosyns, J.-P. Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer? Int. J. Cancer 2002, 101, 500–502.
14. Arlt, V.M.; Alunni-Perret, V.; Quatrehomme, G.; Ohayon, P.; Albano, L.; Gaïd, H.; Michiels, J.-F.; Meyrier, A.; Cassuto, E.; Wiessler, M.; et al. Aristolochic acid (AA)-DNA adduct as marker of AA exposure and risk factor for AA nephropathy-associated cancer. Int. J. Cancer 2004, 111, 977–980.
15. Nortier, J.L.; Pozdzik, A.; Roumeguere, T.; Vanherweghem, J.-L. Néphropathie aux acides aristolochiques (“Néphropathie aux herbes chinoises”). Néphrol. Thér. 2015, 11, 574–588.
16. Mengs, U. Acute toxicity of aristolochic acid in rodents. Arch. Toxicol. 1987, 59, 328–331.
17. Schmeiser, H.H.; Bieler, C.A.; Wiessler, M.; van Ypersele de, S.C.; Cosyns, J.P. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy. Cancer Res. 1996, 56, 2025–2028.
18. Martinez, M.-C.M.; Nortier, J.; Vereerstraeten, P.; Vanherweghem, J.-L. Progression rate of Chinese herb nephropathy: Impact of Aristolochia fangchi ingested dose. Nephrol. Dial. Transplant. 2002, 17, 408–412.
19. Cosyns, J.P.; Goebbels, R.M.; Liberton, V.; Schmeiser, H.H.; Bieler, C.A.; Bernard, A.M. Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats. Arch. Toxicol. 1998, 72, 738–743.
20. Gillerot, G.; Jadoul, M.; Arlt, V.M.; van Ypersele de Strihou, C.; Schmeiser, H.H.; But, P.P.; Bieler, C.A.; Cosyns, J.P. Aristolochic acid nephropathy in a Chinese patient: Time to abandon the term “Chinese herbs nephropathy”? Am. J. Kidney Dis. 2001, 38, E26.
21. Vanherweghem, J.-L. Misuse of Herbal Remedies: The case of an outbreak of terminal renal failure in Belgium (Chinese Herbs Nephropathy). J. Altern. Complement. Med. 1998, 4, 9–13.
22. Pena, J.; Borras, M.; Ramos, J.; Montoliu, J. Rapidly progressive interstitial renal fibrosis due to a chronic intake of a herb (Aristolochia pistolochia) infusion. Nephrol. Dial. Transplant. 1996, 11, 1359–1360.
23. Stengel, B.; Jones, E. End-Stage Renal Insufficiency Associated With Chinese Herbal Consumption in France. Nephrologie 1998, 19, 15–20.
24. Lord, G.M.; Tagore, R.; Cook, T.; Gower, P.; Pusey, C.D. Nephropathy caused by Chinese herbs in the UK. Lancet 1999, 354, 481–482.
25. Krumme, B.; Endmeir, R.; Vanhaelen, M.; Walb, D. Reversible Fanconi syndrome after ingestion of a Chinese herbal “remedy” containing aristolochic acid. Nephrol. Dial. Transplant. 2001, 16, 400–402.
26. Meyer, M.M.; Chen, T.P.; Bennett, W.M. Chinese herb nephropathy. Proc. 2000, 13, 334–337.
27. Chau, W.; Ross, R.; Li, J.Y.Z.; Yong, T.Y.; Klebe, S.; Barbara, J.A. Nephropathy associated with use of a Chinese herbal product containing aristolochic acid. Med. J. Aust. 2011, 194, 367–368.
28. Chen, W.; Chen, Y.; Li, A. The clinical and pathological manifestations of aristolochic acid nephropathy— The report of 58 cases. Zhonghua Yi Xue Za Zhi 2001, 81, 1101–1105.
29. Lo, S.H.K.; Mo, K.L.; Wong, K.S.; Poon, S.P.; Chan, C.K.; Lai, C.K.; Chan, A. Aristolohic acid nephropathy complicating a patient with focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 2004, 19, 1913–1915.
30. Yang, L.; Li, X.; Wang, H. Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis. Nephrol. Dial. Transplant. 2007, 22, 445–456.
31. Yang, L.; Su, T.; Li, X.M.; Wang, X.; Cai, S.Q.; Meng, L.Q.; Zou, W.Z.; Wang, H.Y. Aristolochic acid nephropathy: Variation in presentation and prognosis. Nephrol. Dial. Transplant. 2012, 27, 292–298.
32. Yang, C.S.; Lin, C.H.; Chang, S.H.; Hsu, H.C. Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs. Am. J. Kidney Dis. 2000, 35, 313–318.
33. Lee, C.T.; Wu, M.S.; Lu, K.; Hsu, K.T. Renal tubular acidosis, hypokalemic paralysis, rhabdomyolysis, and acute renal failure—A rare presentation of Chinese herbal nephropathy. Ren. Fail. 1999, 21, 227–230.
34. Hong, Y.T.; Fu, L.S.; Chung, L.H.; Hung, S.C.; Huang, Y.T.; Chi, C.S. Fanconi’s syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs. Pediatr. Nephrol. 2006, 21, 577–579.
35. Tanaka, A.; Nishida R; Sawai, K.; Nagae, T.; Shinkai, S.; Ishikawa, M.; Maeda, K.; Murata, M.; Seta, K.; Okuda, J.; et al. Traditional remedy-induced Chinese herbs nephropathy showing rapid deterioration of renal function. Nihon Jinzo Gakkai Shi 1997, 39, 794–797.
36. Tanaka, A.; Nishida, R.; Maeda, K.; Sugawara, A.; Kuwahara, T. Aristolochic acid—Induced Fanconi’s syndrome and nephropathy presenting as hypokalemic paralysis. Clin. Nephrol. 2000, 39, 521116.
37. Kazama, I.; Matsubara, M.; Michimata, M.; Suzuki, M.; Hatano, R.; Sato, H.; Ito, S. Adult onset Fanconi syndrome: Extensive tubulo-interstitial lesions and glomerulopathy in the early stage of Chinese herbs nephropathy. Clin. Exp. Nephrol. 2004, 8, 283–287.
38. Michl, J.; Jennings, H.M.; Kite, G.C.; Ingrouille, M.J.; Simmonds, M.S.J.; Heinrich, M. Is aristolochic acid nephropathy a widespread problem in developing countries: A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical-phytochemical approach. J. Ethnopharmacol. 2013, 149, 235–244.
39. Lee, S.; Lee, T.; Lee, B.; Choi, H.; Yang, M.; Ihm, C.; Kim, M. Fanconi’s syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acid. Nephrology 2004, 126–129.
40. Poon, W.T.; Lai, C.K.; Chan, A.Y.W. Aristolochic acid nephropathy: The Hong Kong perspective. Hong Kong J. Nephrol. 2007, 9, 7–14.
41. Nortier, J.L.; Vanherweghem, J.-L. For patients taking herbal therapy—Lessons from aristolochic acid nephropathy. Nephrol. Dial. Transplant. 2007, 22, 1512–1517.
42. Heinrich, M.; Chan, J.; Wanke, S.; Neinhuis, C.; Simmonds, M.S.J. Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2—A global assessment based on bibliographic sources. J. Ethnopharmacol. 2009, 125, 108–144.
43. National Toxicology Program. Aristolochic Acids. Rep. Carcinog. 2011, 12, 45–49.
44. Stiborová, M.; Arlt, V.M.; Schmeiser, H.H. Balkan endemic nephropathy: An update on its aetiology. Arch. Toxicol. 2016, 90, 2595–2615.
45. Pavlović, N.M. Balkan endemic nephropathy—Current status and future perspectives. Clin. Kidney J. 2013, 6, 257–265.
46. Batuman, V. Fifty years of Balkan endemic nephropathy: Daunting questions, elusive answers. Kidney Int. 2006, 69, 644–646.
47. Stefanović, V.; Polenaković, M. Fifty years of research in balkan endemic nephropathy: Where are we now? Nephron Clin. Pract. 2009, 112, 51–56.
48. Dimitrov, P.; Tsolova, S.; Georgieva, R.; Bozhilova, D.; Simeonov, V.; Bonev, A.; Karmaus, W. Clinical markers in adult offspring of families with and without Balkan Endemic Nephropathy. Kidney Int. 2006, 69, 723–729.
49. Pavlovic, N.M.; Maksimovic, V.; Maksimovic, J.D.; Orem, W.H.; Tatu, C.A.; Lerch, H.E.; Bunnell, J.E.; Kostic, E.N.; Szilagyi, D.N.; Paunescu, V. Possible health impacts of naturally occurring uptake of aristolochic acids by maize and cucumber roots: Links to the etiology of endemic (Balkan) nephropathy. Environ. Geochem. Health 2013, 35, 215–226.
50. Stefanovic, V.; Radovanovic, Z. Balkan endemic nephropathy and associated urothelial cancer. Nat. Clin. Pract. Urol. 2008, 5, 105–112.
51. Miletić-Medved, M.; Domijan, A.M.; Peraica, M. Recent data on endemic nephropathy and related urothelial tumors in Croatia. Wien. Klin. Wochenschr. 2005, 117, 604–609.
52. Grollman, A.P.; Jelaković, B. Role of environmental toxins in endemic (Balkan) nephropathy. October 2006, Zagreb, Croatia. J. Am. Soc. Nephrol. 2007, 18, 2817–2823.
53. Grollman, A.P. Aristolochic Acid Nephropathy: Harbinger of a Global Iatrogenic Disease. Environ. Mol. Mutagen. 2013, 51, 1–7.
54. Jelaković, B.; Nikolić, J.; Radovanović, Z.; Nortier, J.; Cosyns, J.P.; Grollman, A.P.; Bašić-Jukić, N.; Belicza, M.; Bukvić, D.; Čavaljuga, S.; et al. Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy. Nephrol. Dial. Transplant. 2014, 29, 2020–2027.
55. Arlt, V.M.; Stiborova, M.; Schmeiser, H.H. Aristolochic acid as a probable human cancer hazard in herbal remedies: A review. Mutagenesis 2002, 17, 265–277.
56. Hranjec, T.; Kovac, A.; Kos, J.; Mao, W.; Chen, J.J.; Grollman, A.P.; Jelaković, B. Endemic nephropathy: The case for chronic poisoning by Aristolochia. Croat. Med. J. 2005, 46, 116–125.
57. De Broe, M.E. Chinese herbs nephropathy and Balkan endemic nephropathy: Toward a single entity, aristolochic acid nephropathy. Kidney Int. 2012, 81, 513–515.
58. Arlt, V.M.; Stiborova, M.; vom Brocke, J.; Simoes, M.L.; Lord, G.M.; Nortier, J.L.; Hollstein, M.; Phillips, D.H.; Schmeiser, H.H. Aristolochic acid mutagenesis: Molecular clues to the aetiology of Balkan endemic nephropathy-associated urothelial cancer. Carcinogenesis 2007, 28, 2253–2261.
59. Yun, B.H.; Rosenquist, T.A.; Sidorenko, V.; Iden, C.R.; Chen, C.H.; Pu, Y.S.; Bonala, R.; Johnson, F.; Dickman, K.G.; Grollman, A.P.; et al. Biomonitoring of aristolactam-DNA adducts in human tissues using ultra-performance liquid chromatography/ion-trap mass spectrometry. Chem. Res. Toxicol. 2012, 25, 1119–1131.
60. Chan, W.; Pavlović, N.M.; Li, W.; Chan, C.-K.; Liu, J.; Deng, K.; Wang, Y.; Milosavljević, B.; Kostić, E.N. Quantitation of Aristolochic Acids in Corn, Wheat Grain, and Soil Samples Collected in Serbia: Identifying a Novel Exposure Pathway in the Etiology of Balkan Endemic Nephropathy. J. Agric. Food Chem. 2016, 64, 5928–5934.
61. Li, W.; Hu, Q.; Chan, W. Uptake and Accumulation of Nephrotoxic and Carcinogenic Aristolochic Acids in Food Crops Grown in Aristolochia clematitis-Contaminated Soil and Water. J. Agric. Food Chem. 2016, 64, 107–112.
62. Grollman, A.P.; Shibutani, S.; Moriya, M.; Miller, F.; Wu, L.; Moll, U.; Suzuki, N.; Fernandes, A.; Rosenquist, T.; Medverec, Z.; et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc. Natl. Acad. Sci. USA 2007, 104, 12129–12134.
63. Tanaka, A.; Nishida, R.; Maeda, K.; Sugawara, A.; Kuwahara, T. Chinese herb nephropathy in Japan presents adult-onset Fanconi syndrome: Could different components of aristolochic acids cause a different type of Chinese herb nephropathy? Clin. Nephrol. 2000, 53, 301–306.
64. Reginster, F.; Jadoul, M.; van Ypersele de Strihou, C. Chinese herbs nephropathy presentation, natural history and fate after transplantation. Nephrol. Dial. Transplant. 1997, 12, 81–86.
65. Kabanda, A.; Jadoul, M.; Lauwerys, R.; Bernard, A.; van Ypersele de Strihou, C. Low molecular weight proteinuria in Chinese herbs nephropathy. Kidney Int. 1995, 48, 1571–1576.
66. Nortier, J.L.; Deschodt-Lanckman, M.M.; Simon, S.; Thielemans, N.O.; de Prez, E.G.; Depierreux, M.F.; Tielemans, C.L.; Richard, C.; Lauwerys, R.R.; Bernard, A.M.; et al. Proximal tubular injury in Chinese herbs nephropathy: Monitoring by neutral endopeptidase enzymuria. Kidney Int. 1997, 51, 288–293.
67. Lord, G.M.; Cook, T.; Arlt, V.M.; Schmeiser, H.H.; Williams, G.; Pusey, C.D. Urothelial malignant disease and Chinese herbal nephropathy. Lancet 2001, 358, 1515–1516.
68. Mengs, U.; Lang, W.; Poch, J.A. The carcinogenic action of aristolochic acid in rats. Arch. Toxicol. 1982, 51, 107–119.
69. Mengs, U. Tumor induction in mice following exposure to aristolochic acid. Arch. Toxicol. 1988, 61, 504–505.
70. Cui, M.; Liu, Z.H.; Qiu, Q.; Li, H.; Li, L.S. Tumour induction in rats following exposure to short-term high dose aristolochic acid I. Mutagenesis 2005, 20, 45–49.
71. Cosyns, J.P.; Dehoux, J.P.; Guiot, Y.; Goebbels, R.M.; Robert, A.; Bernard, A.M.; van Ypersele de Strihou, C. Chronic aristolochic acid toxicity in rabbits: A model of Chinese herbs nephropathy? Kidney Int. 2001, 59, 2164–2173.
72. Lemy, A.; Wissing, K.M.; Rorive, S.; Zlotta, A.; Roumeguere, T.; Muniz Martinez, M.C.; Decaestecker, C.; Salmon, I.; Abramowicz, D.; Vanherweghem, J.L.; et al. Late Onset of Bladder Urothelial Carcinoma after Kidney Transplantation for End-Stage Aristolochic Acid Nephropathy: A Case Series With 15-Year Follow-up. Am. J. Kidney Dis. 2008, 51, 471–477.
73. Gokmen, M.; Cosyns, J.; Arlt, V.M.; Stiborova, M.; Phillips, D.; Schmeiser, H.H.; Simmonds, M.S.J.; Cook, T.; Vanherweghem, J.-L.; Nortier, J.; et al. The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy. Ann. Intern. Med. 2013, 158, 469–477.
74. Huang, L.; Scarpellini, A.; Funck, M.; Verderio, E.A.M.; Johnson, T.S. Development of a Chronic Kidney Disease Model in C57BL/6 Mice with Relevance to Human Pathology. Nephron Extra 2013, 33, 12–29.
75. Sato, N.; Takahashi, D.; Chen, S.-M.; Tsuchiya, R.; Mukoyama, T.; Yamagata, S.; Ogawa, M.; Yoshida, M.; Kondo, S.; Satoh, N.; et al. Acute nephrotoxicity of aristolochic acids in mice. J. Pharm. Pharmacol. 2004, 56, 221–229.
76. Nortier, J.L.; Schmeiser, H.H.; Muniz Martinez, M.C.; Arlt, V.M.; Vervaet, C.; Garbar, C.H.; Daelemans, P.; Vabherweghem, J.L. Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristolochic acid may occur without severe renal failure. Nephrol. Dial. Transplant. 2003, 18, 426–428.
77. Dickman, K.G.; Sweet, D.H.; Bonala, R.; Ray, T.; Wu, A. Physiological and molecular characterization of aristolochic acid transport by the kidney. J. Pharmacol. Exp. Ther. 2011, 338, 588–597.
78. Balachandran, P.; Wei, F.; Lin, R.; Khan, I.A.; Pasco, D.S. Structure activity relationships of aristolochic acid analogues: Toxicity in cultured renal epithelial cells. Kidney Int. 2005, 67, 1797–1805.
79. Shibutani, S.; Dong, H.; Suzuki, N.; Ueda, S.; Miller, F.; Grollman, A.P. Selective toxicity of aristolochic acids I and II. Drug Metab. Dispos. 2007, 35, 1217–1222.
80. Krumbiegel, G.; Hallensleben, J.; Mennicke, W.; Rittmann, N.; Roth, H. Studies on the metabolism of aristolochic acids I and II. Xenobiotica 1987, 17, 981–991.
81. Chan, W.; Luo, H.B.; Zheng, Y.; Cheng, Y.K.; Cai, Z. Investigation of the metabolism and reductive activation of carcinogenic aristolochic acids in rats. Drug Metab. Dispos. 2007, 35, 866–874.
82. Leung, E.M.K.; Chan, W. Noninvasive measurement of aristolochic acid-DNA adducts in urine samples from aristolochic acid-treated rats by liquid chromatography coupled tandem mass spectrometry: Evidence for DNA repair by nucleotide-excision repair mechanisms. Mutat. Res. Fundam. Mol. Mech. Mutagen. 2014, 766–767, 1–6.
83. Leung, E.M.K.; Chan, W. Quantification of aristolochic acid-RNA adducts in the urine of aristolochic acid-treated rats by liquid chromatography-tandem mass spectrometry. Chem. Res. Toxicol. 2015, 28, 567–569.
84. Chen, M.; Gong, L.; Qi, X.; Xing, G.; Luan, Y.; Wu, Y.; Xiao, Y.; Yao, J.; Li, Y.; Xue, X.; et al. Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity. Toxicol. Sci. 2011, 122, 288–296.
85. Guo, L.; Wu, H.; Yue, H.; Lin, S.; Lai, Y.; Cai, Z. A novel and specific method for the determination of aristolochic acid-derived DNA adducts in exfoliated urothelial cells by using ultra performance liquid chromatography-triple quadrupole mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2011, 879, 153–158.
86. Babu, E.; Takeda, M.; Nishida, R.; Noshiro-Kofuji, R.; Yoshida, M.; Ueda, S.; Fukutomi, T.; Anzai, N.; Endou, H. Interactions of human organic anion transporters with aristolochic acids. J. Pharmacol. Sci. 2010, 196, 192–196.
87. Hagos, Y.; Wolff, N.A. Assessment of the role of renal organic anion transporters in drug-induced nephrotoxicity. Toxins (Basel) 2010, 2, 2055–2082.
88. Sekine, T.; Miyazaki, H.; Endou, H. Molecular physiology of renal organic anion transporters. Am. J. Physiol. Ren. Physiol. 2006, 290, 251–261.
89. Nigam, S.K.; Bush, K.T.; Martovetsky, G.; Ahn, S.-Y.; Liu, H.C.; Richard, E.; Bhatnagar, V.; Wu, W. The Organic Anion Transporter (OAT) Family: A Systems Biology Perspective. Physiol. Rev. 2015, 95, 83–123.
90. Otani, N.; Ouchi, M.; Hayashi, K.; Jutabha, P.; Anzai, N. Roles of organic anion transporters (OATs) in renal proximal tubules and their localization. Anat. Sci. Int. 2016, doi:10.1007/s12565-016-0369-3.
91. Bakhiya, N.; Arlt, V.M.; Bahn, A.; Burckhardt, G.; Phillips, D.H.; Glatt, H. Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy. Toxicology 2009, 264, 74–79.
92. Ahn, S.-Y.; Nigam, S.K. Toward a systems level understanding of organic anion and other multispecific drug transporters: A remote sensing and signaling hypothesis. Mol. Pharmacol. 2009, 76, 481–490.
93. Anzai, N.; Endou, H. Renal drug transporters and nephrotoxicity. Life Sci. 2008, 447–452.
94. Yin, J.; Wang, J. Renal drug transporters and their significance in drug–drug interactions. Acta Pharm. Sin. B 2016, 6, 363–373.
95. Xue, X.; Gong, L.-K.; Maeda, K.; Luan, Y.; Qi, X.-M.; Sugiyama, Y.; Ren, J. Critical role of organic anion transporters 1 and 3 in kidney accumulation and toxicity of aristolochic acid I. Mol. Pharm. 2011, 8, 2183–2192.
96. Zeng, Y.; Zhang, R.; Wu, J.; Liu, M.; Peng, W.; Yu, X.; Yang, X. Organic anion transporter 1 (OAT1) involved in renal cell transport of aristolochic acid I. Hum. Exp. Toxicol. 2012, 31, 759–770.
97. Baudoux, T.E.R.; Pozdzik, A.A.; Arlt, V.M.; de Prez, E.G.; Antoine, M.-H.; Quellard, N.; Goujon, J.-M.; Nortier, J.L. Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy. Kidney Int. 2012, 82, 1105–1113.
98. Rosenquist, T.A.; Grollman, A.P. Mutational signature of aristolochic acid: Clue to the recognition of a global disease. DNA Repair (Amst.) 2016, 44, 205–211.
99. Stiborová, M.; Frei, E.; Arlt, V.M.; Schmeiser, H.H. Metabolic activation of carcinogenic aristolochic acid, a risk factor for Balkan endemic nephropathy. Mutat. Res. Rev. Mutat. Res. 2008, 658, 55–67.
100. Stiborova, M.; Frei, E.; Arlt, V.M.; Schmeiser, H.H. The role of biotransformation enzymes in the development of renal injury and urothelial cancer caused by aristolochic acid: Urgent questions and difficult answers. Biomed. Pap. 2009, 153, 5–12.
101. Stiborová, M.; Frei, E.; Schmeiser, H.H.; Arlt, V.M.; Martínek, V. Mechanisms of enzyme-catalyzed reduction of two carcinogenic nitro-aromatics, 3-nitrobenzanthrone and aristolochic acid I: Experimental and theoretical approaches. Int. J. Mol. Sci. 2014, 15, 10271–10295.
102. Arlt, V.M.; Levová, K.; Bárta, F.; Shi, Z.; Evans, J.D.; Frei, E.; Schmeiser, H.H.; Nebert, D.W.; Phillips, D.H.; Stiborová, M. Role of P450 1A1 and P450 1A2 in bioactivation versus detoxication of the renal carcinogen aristolochic acid I: Studies in Cyp1a1(−/−), Cyp1a2(−/−), and Cyp1a1/1a2(−/−) mice. Chem. Res. Toxicol. 2011, 24, 1710–1719.
103. Bieler, C.A.; Stiborova, M.; Wiessler, M.; Cosyns, J.P.; van Ypersele de Strihou, C.; Schmeiser, H.H. 32P-post-labelling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy. Carcinogenesis 1997, 18, 1063–1067.
104. Stiborová, M.; Martínek, V.; Frei, E.; Arlt, V.M.; Schmeiser, H.H. Enzymes Metabolizing Aristolochic Acid and their Contribution to the Development of Aristolochic Acid Nephropathy and Urothelial Cancer. Curr. Drug Metab. 2013, 14, 695–705.
105. Milichovký, J.; Bárta, F.; Schmeiser, H.; Arlt, V.; Frei, E.; Stiborová, M.; Martínek, V. Active Site Mutations as a Suitable Tool Contributing to Explain a Mechanism of Aristolochic Acid I Nitroreduction by Cytochromes P450 1A1, 1A2 and 1B1. Int. J. Mol. Sci. 2016, 17, 213.
106. Schmeiser, H.H.; Nortier, J.L.; Singh, R.; da Costa, G.G.; Sennesael, J.; Cassuto-Viguier, E.; Ambrosetti, D.; Rorive, S.; Pozdzik, A.; Phillips, D.H.; et al. Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy. Int. J. Cancer 2014, 135, 502–507.
107. Yun, B.H.; Sidorenko, V.S.; Rosenquist, T.A.; Dickman, K.G.; Grollman, A.P.; Turesky, R.J. New Approaches for Biomonitoring Exposure to the Human Carcinogen Aristolochic Acid. Toxicol. Res. (Camb.) 2015, 4, 763–776.
108. Leung, E.M.K.; Chan, W. Comparison of DNA and RNA Adduct Formation: Significantly Higher Levels of RNA than DNA Modifications in the Internal Organs of Aristolochic Acid-Dosed Rats. Chem. Res. Toxicol. 2015, 28, 248–255.
109. Lebeau, C.; Debelle, F.D.; Arlt, V.M.; Pozdzik, A.; De Prez, E.G.; Phillips, D.H.; Deschodt-Lanckman, M.M.; Vanherweghem, J.L.; Nortier, J.L. Early proximal tubule injury in experimental aristolochic acid nephropathy: Functional and histological studies. Nephrol. Dial. Transplant. 2005, 20, 2321–2332.
110. Declèves, A.-E.; Jadot, I.; Colombaro, V.; Martin, B.; Voisin, V.; Nortier, J.; Caron, N. Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury: An old friend with new assets. Exp. Physiol. 2016, 101, 193–206.
111. Pozdzik, A.A.; Salmon, I.J.; Husson, C.P.; Decaestecker, C.; Rogier, E.; Bourgeade, M.-F.; Deschodt-Lanckman, M.M.; Vanherweghem, J.-L.; Nortier, J.L. Patterns of interstitial inflammation during the evolution of renal injury in experimental aristolochic acid nephropathy. Nephrol. Dial. Transplant. 2008, 23, 2480–2491.
112. Pozdzik, A.A.; Salmon, I.J.; Debelle, F.D.; Decaestecker, C.; van den Branden, C.; Verbeelen, D.; Deschodt-Lanckman, M.M.; Vanherweghem, J.-L.; Nortier, J.L. Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation. Kidney Int. 2008, 73, 595–607.
113. Diamond, J.R.; Pallone, T.L. Acute interstitial nephritis following use of tung shueh pills. Am. J. Kidney Dis. 1994, 24, 219–221.
114. Jelaković, B.; Karanović, S.; Vuković-Lela, I.; Miller, F.; Edwards, K.L.; Nikolić, J.; Tomić, K.; Slade, N.; Brdar, B.; Turesky, R.J.; et al. Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid. Kidney Int. 2012, 81, 559–567.
115. Schmeiser, H.H.; Janssen, J.W.G.; Lyons, J.; Scherf, H.R.; Pfau, W.; Buchmann, A.; Bartram, C.R.; Wiessler, M. Aristolochic Acid Activates ras Genes in Rat Tumors at Deoxyadenosine Residues. Cancer Res. 1990, 50, 5464–5469.
116. Lord, G.M.; Hollstein, M.; Arlt, V.M.; Roufosse, C.; Pusey, C.D.; Cook, T.; Schmeiser, H.H. DNA adducts and p53 mutations in a patient with aristolochic acid-associated nephropathy. Am. J. Kidney Dis. 2004, 43, e18.1–e18.7.
117. Hollstein, M.; Moriya, M.; Grollman, A.P.; Olivier, M. Analysis of TP53 mutation spectra reveals the fingerprint of the potent environmental carcinogen, aristolochic acid. Mutat. Res. Rev. Mutat. Res. 2013, 753, 41–49.
118. Slade, N.; Moll, U.M.; Brdar, B.; Zorić, A.; Jelaković, B. p53 mutations as fingerprints for aristolochic acid—An environmental carcinogen in endemic (Balkan) nephropathy. Mutat. Res. Fundam. Mol. Mech. Mutagen. 2009, 663, 1–6.
119. Hoang, M.L.; Chen, C.-H.; Sidorenko, V.S.; He, J.; Dickman, K.G.; Yun, B.H.; Moriya, M.; Niknafs, N.; Douville, C.; Karchin, R.; et al. Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing. Sci. Transl. Med. 2013, 5, 197ra102.
120. Moriya, M.; Slade, N.; Brdar, B.; Medverec, Z.; Tomic, K.; Jelaković, B.; Wu, L.; Truong, S.; Fernandes, A.; Grollman, A.P. TP53 Mutational signature for aristolochic acid: An environmental carcinogen. Int. J. Cancer 2011, 129, 1532–1536.
121. Aydin, S.; Dekairelle, A.-F.; Ambroise, J.; Durant, J.-F.; Heusterspreute, M.; Cosyns, Y.G.J.-P.; Gala, J.-L. Unambiguous Detection of Multiple TP53 Gene Mutations in AAN-Associated Urothelial Cancer in Belgium Using Laser Capture Microdissection. PLoS ONE 2014, 9, e106301.
122. Yu, F.-Y.; Wu, T.-S.; Chen, T.-W.; Liu, B.-H. Aristolochic acid I induced oxidative DNA damage associated with glutathione depletion and ERK1/2 activation in human cells. Toxicol. In Vitro 2011, 25, 810–816.
123. Romanov, V.; Whyard, T.C.; Waltzer, W.C.; Grollman, A.P.; Rosenquist, T. Aristolochic acid-induced apoptosis and G2 cell cycle arrest depends on ROS generation and MAP kinases activation. Arch. Toxicol. 2015, 89, 47–56.
124. Wu, T.K.; Wei, C.W.; Pan, Y.R.; Cherng, S.H.; Chang, W.J.; Wang, H.F.; Yu, Y.L. Vitamin C attenuates the toxic effect of aristolochic acid on renal tubular cells via decreasing oxidative stress mediated cell death pathways. Mol. Med. Rep. 2015, 12, 6086–6092.
125. Bunel, V.; Antoine, M.-H.; Stévigny, C.; Nortier, J.; Duez, P. New in vitro insights on a cell death pathway induced by magnolol and honokiol in aristolochic acid tubulotoxicity. Food Chem. Toxicol. 2016, 87, 77–87.
126. Li, Y.C.; Tsai, S.H.; Chen, S.M.; Chang, Y.M.; Huang, T.C.; Huang, Y.P.; Chang, C.T.; Lee, J.A. Aristolochic acid-induced accumulation of methylglyoxal and N-(carboxymethyl)lysine: An important and novel pathway in the pathogenic mechanism for aristolochic acid nephropathy. Biochem. Biophys. Res. Commun. 2012, 423, 832–837.
127. Huang, T.C.; Chen, S.-M.; Li, Y.-C.; Lee, J.-A. Increased renal semicarbazide-sensitive amine oxidase activity and methylglyoxal levels in aristolochic acid-induced nephrotoxicity. Life Sci. 2014, 114, 4–11.
128. Okada, H.; Watanabe, Y.; Inoue, T.; Kobayashi, T.; Kanno, Y.; Shiota, G.; Nakamura, T.; Sugaya, T.; Fukamizu, A.; Suzuki, H. Transgene-derived hepatocyte growth factor attenuates reactive renal fibrosis in aristolochic acid nephrotoxicity. Nephrol. Dial. Transplant. 2003, 18, 2515–2523.
129. Hsin, Y.H.; Cheng, C.H.; Tzen, J.T.C.; Wu, M.J.; Shu, K.H.; Chen, H.C. Effect of aristolochic acid on intracellular calcium concentration and its links with apoptosis in renal tubular cells. Apoptosis 2006, 11, 2167–2177.
130. Qi, X.; Cai, Y.; Gong, L.; Liu, L.; Chen, F.; Xiao, Y.; Wu, X.; Li, Y.; Xue, X.; Ren, J. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid. Toxicol. Appl. Pharmacol. 2007, 222, 105–110.
131. Liu, M.C.; Maruyama, S.; Mizuno, M.; Morita, Y.; Hanaki, S.; Yuzawa, Y.; Matsuo, S. The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its aristolochic acids. Clin. Exp. Nephrol. 2003, 7, 186–194.
132. Zhou, L.; Fu, P.; Huang, X.R.; Liu, F.; Lai, K.N.; Lan, H.Y. Activation of p53 promotes renal injury in acute aristolochic acid nephropathy. J. Am. Soc. Nephrol. 2010, 21, 31–41.
133. Shi, M.; Ma, L.; Zhou, L.; Fu, P. Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy. Molecules 2016, 21, 1391.
134. Debelle, F.D.; Nortier, J.L.; Husson, C.P.; de Prez, E.G.; Vienne, A.R.; Rombaut, K.; Salmon, I.J.; Deschodt-Lanckman, M.M.; Vanherweghem, J.-L. The renin-angiotensin system blockade does not prevent renal interstitial fibrosis induced by aristolochic acids. Kidney Int. 2004, 66, 1815–1825.
135. Pozdzik, A.A.; Berton, A.; Schmeiser, H.H.; Missoum, W.; Decaestecker, C.; Salmon, I.J.; Vanherweghem, J.L.; Nortier, J.L. Aristolochic acid nephropathy revisited: A place for innate and adaptive immunity? Histopathology 2010, 56, 449–463.
136. Wen, Y.-J.; Qu, L.; Li, X.-M. Ischemic injury underlies the pathogenesis of aristolochic acid-induced acute kidney injury. Transl. Res. 2008, 152, 38–46.
137. Vanherweghem, J.L. Renal failure and urinary tract carcinoma secondary to the intake of certain Chinese herbal medicines. Med. Sci. 2002, 18, 1095–1101.
138. Sun, D.; Feng, J.; Dai, C.; Sun, L.; Jin, T.; Ma, J.; Wang, L. Role of peritubular capillary loss and hypoxia in progressive tubulointerstitial fibrosis in a rat model of aristolochic acid nephropathy. Am. J. Nephrol. 2006, 26, 363–371.
139. Zuk, A.; Bonventre, J. Acute Kidney Injury. Annu. Rev. Med. 2016, 67, 293–307.
140. Gewin, L. NO clue to pathogenesis of aristolochic acid nephropathy. Exp. Physiol. 2016, 101, 33.
141. Li, J.; Zhang, Z.; Wang, D.; Wang, Y.; Li, Y.; Wu, G. TGF-β 1/Smads signaling stimulates renal interstitial fibrosis in experimental AAN. J. Recept. Signal Transduct. Res. 2009, 29, 280–285.
142. Wang, Y.; Zhang, Z.; Shen, H.; Lu, Y.; Li, H.; Ren, X.; Wu, G. TGF-β1/Smad7 Signaling Stimulates Renal Tubulointerstitial Fibrosis Induced by AAI. J. Recept. Signal Transduct. 2008, 28, 413–428.
143. Zhou, L.; Fu, P.; Huang, X.R.; Liu, F.; Chung, A.C.K.; Lai, K.N.; Lan, H.Y. Mechanism of chronic aristolochic acid nephropathy: Role of Smad3. Am. J. Physiol. Ren. Physiol. 2010, 298, F1006–F1017.
144. Dai, X.-Y.; Zhou, L.; Huang, X.-R.; Fu, P.; Lan, H.-Y. Smad7 protects against chronic aristolochic acid nephropathy in mice. Oncotarget 2015, 6, 11930–11944.
145. Antoine, M.-H.; Debelle, F.; Piccirilli, J.; El Kaddouri, F.; Declèves, A.-E.; De Prez, E.; Husson, C.; Mies, F.; Bourgeade, M.-F.; Nortier, J.L. Human bone morphogenetic protein-7 does not counteract aristolochic acid-induced renal toxicity. J. Appl. Toxicol. 2015, 35, 1520–1530.
146. Samarakoon, R.; Rehfuss, A.; Khakoo, N.S.; Falke, L.L.; Dobberfuhl, A.D.; Helo, S.; Overstreet, J.M.; Goldschmeding, R.; Higgins, P.J. Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair. FASEB J. 2016, 30, 3308–3320.
147. Pozdzik, A.A.; Giordano, L.; Li, G.; Antoine, M.-H.; Quellard, N.; Godet, J.; de Prez, E.; Husson, C.; Declèves, A.-E.; Arlt, V.M.; et al. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats. PLoS ONE 2016, 11, e0157288.
148. Dai, X.Y.; Huang, X.R.; Zhou, L.; Zhang, L.; Fu, P.; Manthey, C. Targeting c-fms kinase attenuates chronic aristolochic acid nephropathy in mice. Oncotarget 2016, 7, 10841–10856.
149. Chawla, L.S.; Amdur, R.L.; Amodeo, S.; Kimmel, P.L.; Palant, C.E. The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int. 2011, 79, 1361–1369.
150. Chawla, L.S.; Eggers, P.W.; Star, R.A.; Kimmel, P.L. Acute kidney injury and chronic kidney disease as interconnected syndromes. N. Engl. J. Med. 2014, 371, 58–66.