1. bookVolumen 73 (2022): Edición 1 (March 2022)
Detalles de la revista
License
Formato
Revista
eISSN
1848-6312
Primera edición
26 Mar 2007
Calendario de la edición
4 veces al año
Idiomas
Inglés
access type Acceso abierto

Ochratoxin A potentiates citrinin accumulation in kidney and liver of rats

Publicado en línea: 07 Apr 2022
Volumen & Edición: Volumen 73 (2022) - Edición 1 (March 2022)
Páginas: 43 - 47
Recibido: 01 Oct 2021
Aceptado: 01 Feb 2022
Detalles de la revista
License
Formato
Revista
eISSN
1848-6312
Primera edición
26 Mar 2007
Calendario de la edición
4 veces al año
Idiomas
Inglés
Abstract

Okratoksin A(OTA) i citrinin (CTN) nefrotoksični su mikotoksini koji zajednički kontaminiraju žitarice. Cilj ovoga istraživanja bio je izmjeriti koncentraciju OTA-e i CTN-a u bubrezima i jetri štakora, tretiranih tim mikotoksinima, te provjeriti hoće li tretman resveratrolom (RSV) smanjiti koncentraciju mikotoksina u tkivima. Istraživanje je provedeno na mužjacima štakora soja Wistar, koji su 21 dan bili tretirani OTA-om (0,125 i 0,250 mg/kg t. m.), a dva dana CTN-om (20 mg/kg t. m.) ili kombinacijama tih mikotoksina. Dvije skupine štakora koje su tretirane mikotoksinima OTA+CTN dobivale su 21 dan RSV (20 mg/kg t. m.). Povećanje koncentracija OTA-e u bubrezima i jetri bio je u skladu s povećanjem doze. Tretman mikotoksinima OTA+CTN smanjio je nakupljanje OTA-e u bubrezima i jetri, a povećao je koncentraciju CTN-a. Tretman RSV-om povećao je koncentraciju OTA-e u bubrezima i jetri, ali je smanjio koncentraciju CTN-a u bubrezima tretiranih štakora. Koncentracija OTA-e značajno se smanjila u prisutnosti CTN-a, vjerojatno zbog kompeticije CTN-a i OTA-e za prijenosnike OAT1 i 3, koji služe za prijenos tih toksina kroz membrane u bubrezima.

Key words

Ključne riječi

Mycotoxins ochratoxin A (OTA) and citrinin (CTN) are produced by Aspergillus and Penicillium strains and are often found together in grain. Their co-occurrence in food and feed may be the consequence of contamination with several moulds or one mould species producing both mycotoxins such as P. verrucosum (1, 2, 3, 4). Mandatory OTA monitoring in various commodities in the EU has given a rather good insight into human exposure to this mycotoxin (5). CTN monitoring, in contrast, is not mandatory, despite the recommendation issued by the European Food Safety Authority (6), and data on its levels in food and feed are limited. Grain contamination with CTN is usually low (<10 % of positive samples), but its levels tend to be high (1.1–33 times higher than those of OTA) (7). In Croatia contamination is high (50–75 % samples), with a considerably large level range (0–400 μg/kg) (8, 9). In Bangladesh (10) and Germany (11) a very high percentage of CTN-positive samples was found in human urine, indicating substantial exposure to this mycotoxin (10, 11).The biological half-life of OTA is long, which increases the possibility of OTA interaction with other mycotoxins. In rat plasma it is 120 h and in human plasma 35.5 days (12, 13). Being a small molecule, OTA enters the enterohepatic circulation, gets redistributed across organs, and accumulates in the kidney (14). Its renal excretion by glomerular filtration is limited and involves organic anion transporters (OATs) either on the basolateral or apical side of cells in kidney tubules (15).

Target organs of OTA toxicity are the kidney and liver, but it is also immunotoxic, teratogenic, and carcinogenic.

The toxicological properties of CTN have been summarised elsewhere (16), but, generally, it is considered less nephrotoxic than OTA (8). However, CTN could become equally toxicologically important as OTA if the climate change increases CTN production by P. verrucosum. Studies of its mutagenicity are inconclusive and studies of its carcinogenicity are lacking. Some have found it genotoxic (17, 18, 19), and others not (20, 21).

The aim of our study was to establish the accumulation of OTA and CTN in the kidney and liver of rats and see how it would be affected in combined exposure. We also wanted to see how resveratrol (RSV) would affect organ accumulation of these mycotoxins, as this antioxidant is known to inhibit the expression of organic anion transporters (OATs) 1 and 3 (22, 23). This study was a part of a larger study investigating the effects of these two mycotoxins on oxidative stress in rat kidney, liver, and plasma (24).

Materials and methods

Ketamine hydrochloride and xylazine hydrochloride used in combination to anaesthetise the rats were purchased under brand names Narketan and Xylapan from Chassot AG (Bern, Switzerland). OTA, CTN, and methanol were purchased from Sigma (St. Louis, MO, USA). Ultrapure water (18 MW) was obtained from a Milli-Q Smart2pure 3 UV/UF gradient water purification system (Thermo Fisher Scientific, Waltham, MA, USA). Acetic acid (p. a.) was obtained from Merck (Darmstadt, Germany). Other chemicals and reagents were of analytical grade, and their commercial source is indicated with the description of specific methods.

Adult male Wistar rats (10 weeks old, 230–270 g bw) were kept in makrolon cages at room temperature of 22 °C and 12-hour day/ night cycles and had free access to tap water and standard pelleted food (Mucedola, Settimo Milanese, Italy). Animals were divided into eight groups (N=6 each) as follows: controls (receiving 51 mmol/L NaHCO3), OTA125 (receiving 125 μg/kg bw of OTA alone), OTA250 (receiving 250 μg/kg bw of OTA alone), CTN (receiving 20 mg/ kg bw of CTN alone), OTA125+CTN, OTA250+CTN, OTA125+CTN+RSV (20 mg/kg bw), and OTA250+CTN+RSV. OTA was given dissolved in 51 mmol/L NaHCO3 by gavage every day for 21 days. CTN was dissolved in 50 mmol/L Na2CO3 and given by gavage for two days (CTN alone group), which in combined treatment coincided with the last two days of treatment with OTA and RSV every day between 8 and 9 AM. Animals were sacrificed under general anaesthesia with ketamine and xylazine.

Animal experiments were approved by the Ethics Committee of the Institute for Medical Research and Occupational Health in accordance with the EC Council Directive 2010/63/EU (25).

Organs were taken and kept at -80 °C until analysis. Samples were prepared according to the method described previously and modified for these samples accordingly (26).

Chromatographic analysis of OTA and CTN was run on a tandem quadrupole ultra performance liquid chromatography/ tandem mass spectrometry system (ACQUITY TQD UPLC-MS/ MS, Waters, Milford, MA, USA). Separation was done on a Hibar™ Purospher STAR HR 50x2.1 mm column (Merck, Darmstadt, Germany), 2 μm particle size, and flow rate of 0.53 mL/min. Gradient elution was applied (eluent A – 0.1 % acetic acid; eluent B– methanol) according to the following program: 0–0.61 min – 95 % A; 0.61–4.5 min – 5 % A; 4.5–5 min – 95 % A. The chromatographic run was 7 min per sample. Molecular ions were obtained with electrospray ionisation (positive mode for OTA and negative for CTN). The temperature of the ionisation source was maintained at 115 °C and the temperature of the desolvation gas at 350 °C. Cone gas flow was 60 L/h, and desolvation gas flow 750 L/h. Capillary and cone voltages were maintained at 3.5 kV and ±40 V respectively. Quadrupoles were set to the multiple reaction monitoring (MRM) mode. Each compound was confirmed by the presence of the parent ion and two transitional products. Specific transitions of the precursor ion and product ion were as follows: 249.1 ->177.3 and 249.1->205.4 m/z for CTN and 404->221 and 404->239 m/z for OTA, respectively. Quantification transitions were 249.1->205.4 m/z for CTN and 404->239 m/z for OTA. Optimised collision energy (CE) was 22 and 15 eV for CTN and 20 eV for OTA. Dwell times for each MRM were 0.15 s. Retention times were 3.3 min for CTN and 3.4 min for OTA.

For calibration tissue extracts were spiked with OTA and CTN as follows: 0.1, 1, 10, and 20 μg/kg of the sample for OTA and 0.1, 1, 2, and 10 μg/kg of the sample for CTN. The resulting calibration curves were used for quantification. The established quantification limits of the analytical method were 0.5 μg/kg for OTA, and 0.8 μg/kg for CTN, with a relative standard deviation of reproducibility below 5 % for both compounds. Coefficients of determination (R2) were 0.997 and 0.996 for OTA and CTN, respectively.

Statistical analysis

Data were analysed and plotted with the GraphPad Prism for Windows version 5 (San Diego, CA, USA) and R statistical software version 3.3.1 (The R Foundation for Statistical Computing, Vienna, Austria). OTA and CTN values are presented as medians and interquartile ranges, and were analysed using a nonparametric version of Tukey’s multiple comparison test. All applied tests were two-tailed. P values of less than or equal to 0.05 were considered statistically significant.

Results
OTA and CTN concentrations

The increase in OTA concentrations in both organs was dose-dependent (Figures 1 and 2). Kidney OTA levels in the OTA125+CTN and OTA250+CTN were significantly lower than in the groups receiving respective doses of OTA alone. This effect was also observed in the liver of animals receiving the higher OTA dose.

Figure 1

Kidney ochratoxin A levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from OTA125 alone; b different from OTA125+CTN; c different from OTA250 alone; d different from OTA250+CTN (P<0.05)

Figure 2

Liver ochratoxin A levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from OTA125 alone; b different from OTA125+CTN; c different from OTA250 alone (P<0.05)

RSV did not lower OTA levels in animals receiving OTA+CTN+RSV compared to those receiving OTA+CTN regardless of the OTA dose. In fact, it increased kidney OTA in the OTA250+CTN+RSV group and liver OTA in the OTA125+CTN+RSV group.

Kidney and liver CTN levels in animals receiving OTA+CTN were three to six times higher than in respective tissues of animals receiving CTN alone (Figures 3 and 4).

Figure 3

Kidney citrinin levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/ kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from CTN alone; b different from OTA250+CTN (P<0.05)

Figure 4

Liver citrinin levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/ kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from CTN alone (P<0.05)

RSV lowered kidney CTN in the OTA250+CTN+RSV group compared to the OTA250+CTN treatment.

Discussion

We found that OTA accumulation in the kidney was dose-dependent and comparable with our previous studies (27). Our main finding that OTA levels significantly dropped in both organs in the presence of CTN (Figures 1 and 2) supports in vitro findings that CTN competes with OTA for human OAT1 and 3 with different Ki values (3080 and 15.4 μmol/L, respectively) and that these two transporters have higher affinity for CTN than for OTA (28). Similar findings have also been reported in immortalised human proximal tubule cells in the presence of CTN (29) in which OTA dropped by over 60 %. In another study (30) in which rats received ten times lower doses than in ours for 21 days, CTN levels did not change and CTN did not affect Oat1 and Oat3 protein expression, but OTA250 significantly downregulated Oat2 protein expression in the kidney. In addition, both mycotoxins downregulated Oat5 protein expression. All this suggests that high doses of OTA or both mycotoxins together inhibit kidney transporters involved in the excretion of CTN. There are no reports of transporters responsible for CTN excretion from the liver.

RSV lowered kidney CTN levels in animals treated with OTA250+CTN+RSV compared to OTA250+CTN treatment but increased liver OTA in animals receiving OTA125+CTN. Reports on RSV transport suggest that RSV and its conjugates are the substrates of OAT transporters involved in the transport of OTA and CTN in the kidney (15, 31, 32). RSV was also reported to inhibit OAT1 and 3 when combined with methotrexate (MTX) (33). The same mechanism probably regulates OTA and CTN accumulation in the kidney. However, further mycotoxin interaction studies in doses closer to natural exposure are needed to pinpoint the exact mechanisms of toxicity and their transport through membranes.

Figure 1

Kidney ochratoxin A levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from OTA125 alone; b different from OTA125+CTN; c different from OTA250 alone; d different from OTA250+CTN (P<0.05)
Kidney ochratoxin A levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from OTA125 alone; b different from OTA125+CTN; c different from OTA250 alone; d different from OTA250+CTN (P<0.05)

Figure 2

Liver ochratoxin A levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from OTA125 alone; b different from OTA125+CTN; c different from OTA250 alone (P<0.05)
Liver ochratoxin A levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from OTA125 alone; b different from OTA125+CTN; c different from OTA250 alone (P<0.05)

Figure 3

Kidney citrinin levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/ kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from CTN alone; b different from OTA250+CTN (P<0.05)
Kidney citrinin levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/ kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from CTN alone; b different from OTA250+CTN (P<0.05)

Figure 4

Liver citrinin levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/ kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from CTN alone (P<0.05)
Liver citrinin levels in rats treated with OTA doses of 125 μg/kg bw (OTA125) or 250 μg/ kg bw (OTA250) alone or in combination with citrinin (CTN) and resveratrol (RSV), both in the dose of 20 mg/kg bw. a different from CTN alone (P<0.05)

Schatzmayr G, Streit E. Global occurrence of mycotoxins in the food and feed chain: facts and figures. World Mycotoxin J 2013;6:213–22. doi: 10.3920/WMJ2013.1572 Schatzmayr G Streit E Global occurrence of mycotoxins in the food and feed chain: facts and figures World Mycotoxin J 20136213 22 10.3920/WMJ2013.1572Abierto DOISearch in Google Scholar

Bragulat MR, Martínez E, Castellá G, Cabañes FJ. Ochratoxin A and citrinin producing species of the genus Penicillium from feedstuffs. Int J Food Microbiol 2008;126:43–8. doi: 10.1016/j.ijfoodmicro.2008.04.034 Bragulat MR Martínez E Castellá G Cabañes FJ Ochratoxin A and citrinin producing species of the genus Penicillium from feedstuffs Int J Food Microbiol 200812643 8 10.1016/j.ijfoodmicro.2008.04.03418571755Abierto DOISearch in Google Scholar

Scott PM, Van Walbeek W, Kennedy B, Anyeti D. Mycotoxins (ochratoxin A, citrinin, and sterigmatocystin) and toxigenic fungi in grains and other agricultural products. J Agric Food Chem 1972;20:1103–9. doi: 10.1021/jf60184a010 Scott PM Van Walbeek W Kennedy B Anyeti D Mycotoxins (ochratoxin A, citrinin, and sterigmatocystin) and toxigenic fungi in grains and other agricultural products J Agric Food Chem 1972201103 9 10.1021/jf60184a0105083521Abierto DOISearch in Google Scholar

Ostry V, Malir F, Ruprich J. Producers and important dietary sources of ochratoxin A and citrinin. Toxins (Basel) 2013;5:1574–86. doi: 10.3390/toxins5091574 Ostry V Malir F Ruprich J Producers and important dietary sources of ochratoxin A and citrinin Toxins (Basel) 201351574 86 10.3390/toxins5091574379887424048364Abierto DOISearch in Google Scholar

COMMISSION REGULATION (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs [displayed 16 February 2022]. Available at https://eur-lex.e u r o p a . e u / L e x U r i S e r v / L e x U r i S e r v. do?uri=OJ:L:2006:364:0005:0024:EN:PDF COMMISSION REGULATION (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs [displayed 16 February 2022] Available at https://eur-lex.e u r o p a . e u / L e x U r i S e r v / L e x U r i S e r v. do?uri=OJ:L:2006:364:0005:0024:EN:PDFSearch in Google Scholar

Böhm J, De Saeger S, Edler L, Fink-Gremmels J, Mantle P, Peraica M, Štětina R, Vrabcheva T. Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed. EFSA J 2012;10:2605. doi :10.2903/j.efsa.2012.2605 Böhm J De Saeger S Edler L Fink-Gremmels J Mantle P Peraica M Štětina R Vrabcheva T Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed EFSA J 2012102605 10.2903/j.efsa.2012.260510.2903/j.efsa.2012.2605Search in Google Scholar

Kononenko GP, Burkin AA. Peculiarities of feed contamination with citrinin and ochratoxin A. Agric Sci 2013;4:34–8. doi: 10.4236/as.2013.41006 Kononenko GP Burkin AA Peculiarities of feed contamination with citrinin and ochratoxin A Agric Sci 2013434 8 10.4236/as.2013.41006Abierto DOISearch in Google Scholar

Pleadin J, Frece J, Kudumija N, Petrović D, Vasilj V, Zadravec M, Škrivanko M, Perković I, Markov K. Citrinin in cereals and feedstuffs coming from Croatia and Bosnia & Herzegovina. Food Addit Contam Part B Surveill 2016;9:268–74. doi: 10.1080/19393210.2016.1210242 Pleadin J Frece J Kudumija N Petrović D Vasilj V Zadravec M Škrivanko M Perković I Markov K Citrinin in cereals and feedstuffs coming from Croatia and Bosnia & Herzegovina Food Addit Contam Part B Surveill 20169268 74 10.1080/19393210.2016.121024227409398Abierto DOISearch in Google Scholar

Čulig B, Bevardi M, Bošnir J, Serdar S, Lasić D, Racz A, Galić A, Kuharić Ž. Presence of citrinin in grains and its possible health effects. Afr J Tradit Complement Altern Med 2017;14:22–30. doi: 10.21010/AJTCAM.V14I3.3 Čulig B Bevardi M Bošnir J Serdar S Lasić D Racz A Galić A Kuharić Ž Presence of citrinin in grains and its possible health effects Afr J Tradit Complement Altern Med 20171422 30 10.21010/AJTCAM.V14I3.3Abierto DOISearch in Google Scholar

Ali N, Blaszkewicz M, Mohanto NC, Rahman M, Alim A, Hossain K, Degen GH. First results on citrinin biomarkers in urines from rural and urban cohorts in Bangladesh. Mycotoxin Res 2015;31:9–16. doi: 10.1007/s12550-014-0217-z Ali N Blaszkewicz M Mohanto NC Rahman M Alim A Hossain K Degen GH First results on citrinin biomarkers in urines from rural and urban cohorts in Bangladesh Mycotoxin Res 2015319 16 10.1007/s12550-014-0217-z25488509Abierto DOISearch in Google Scholar

Ali N, Blaszkewicz M, Degen GH. Occurrence of the mycotoxin citrinin and its metabolite dihydrocitrinone in urines of German adults. Arch Toxicol 2015;89:573–8. doi: 10.1007/s00204-014-1363-y Ali N Blaszkewicz M Degen GH Occurrence of the mycotoxin citrinin and its metabolite dihydrocitrinone in urines of German adults Arch Toxicol 201589573 8 10.1007/s00204-014-1363-y25224402Abierto DOISearch in Google Scholar

Hagelberg S, Hult K, Fuchs R. Toxicokinetics of ochratoxin A in several species and its plasma-binding properties. J Appl Toxicol 1989;9:91–6. doi: 10.1002/jat.2550090204 Hagelberg S Hult K Fuchs R Toxicokinetics of ochratoxin A in several species and its plasma-binding properties J Appl Toxicol 1989991 6 10.1002/jat.2550090204Abierto DOISearch in Google Scholar

Studer-Rohr I, Schlatter J, Dietrich DR. Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans. Arch Toxicol 2000;74:499–510. doi: 10.1007/s002040000157 Studer-Rohr I Schlatter J Dietrich DR Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans Arch Toxicol 200074499 510 10.1007/s002040000157Abierto DOISearch in Google Scholar

Fuchs R, Radić B, Peraica M, Hult K, Pleština R. Enterohepatic circulation od ochratoxin A in rats. Period Biol 1988;90:39–42. Fuchs R Radić B Peraica M Hult K Pleština R Enterohepatic circulation od ochratoxin A in rats Period Biol 19889039 42Search in Google Scholar

Žlender V, Breljak D, Ljubojević M, Flajs D, Balen D, Brzica H, Domijan A-M, Peraica M, Fuchs R, Anzai N, Sabolić I. Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex. Toxicol Appl Pharmacol 2009;239:284–96. doi: 10.1016/j.taap.2009.06.008 Žlender V Breljak D Ljubojević M Flajs D Balen D Brzica H Domijan A-M Peraica M Fuchs R Anzai N Sabolić I Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex Toxicol Appl Pharmacol 2009239284 96 10.1016/j.taap.2009.06.008Abierto DOISearch in Google Scholar

Flajs D, Peraica M. Toxicological properties of citrinin. Arh Hig Rada Toksikol 2009;60:457–64. doi: 10.2478/10004-1254-60-2009-1992 Flajs D Peraica M Toxicological properties of citrinin Arh Hig Rada Toksikol 200960457 64 10.2478/10004-1254-60-2009-1992Abierto DOISearch in Google Scholar

Šegvić Klarić M, Zelježić D, Rumora L, Peraica M, Pepeljnjak S, Domijan A-M. A potential role of calcium in apoptosis and aberrant chromatin forms in porcine kidney PK15 cells induced by individual and combined ochratoxin A and citrinin. Arch Toxicol 2012;86:97–107. doi: 10.1007/s00204-011-0735-9 Šegvić Klarić M Zelježić D Rumora L Peraica M Pepeljnjak S Domijan A-M A potential role of calcium in apoptosis and aberrant chromatin forms in porcine kidney PK15 cells induced by individual and combined ochratoxin A and citrinin Arch Toxicol 20128697 107 10.1007/s00204-011-0735-9Abierto DOISearch in Google Scholar

Bouslimi A, Bouaziz C, Ayed-Boussema I, Hassen W, Bacha H. Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells. Toxicology 2008;251:1–7. doi: 10.1016/j.tox.2008.06.008 Bouslimi A Bouaziz C Ayed-Boussema I Hassen W Bacha H Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells Toxicology 20082511 7 10.1016/j.tox.2008.06.008Abierto DOISearch in Google Scholar

Jeswal P. Citrinin-induced chromosomal abnormalities in the bone marrow cells of Mus musculus. Cytobios 1996;86:29–33. PMID: 8952057 Jeswal P Citrinin-induced chromosomal abnormalities in the bone marrow cells of Mus musculus Cytobios 19968629 33 PMID: 8952057Search in Google Scholar

Liu B-H, Yu F-Y, Wu T-S, Li S-Y, Su M-C, Wang M-C, Shih S-M. Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin. Toxicol Appl Pharmacol 2003;191:255–63. doi: 10.1016/S0041-008X(03)00254-0 Liu B-H Yu F-Y Wu T-S Li S-Y Su M-C Wang M-C Shih S-M Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin Toxicol Appl Pharmacol 2003191255 63 10.1016/S0041-008X(03)00254-0Abierto DOISearch in Google Scholar

Knasmüller S, Cavin C, Chakraborty A, Darroudi F, Majer BJ, Huber WW, Ehrlich VA. Structurally related mycotoxins ochratoxin A, ochratoxin B, and citrinin differ in their genotoxic activities and in their mode of action in human-derived liver (HepG2) cells: implications for risk assessment. Nutr Cancer 2004;50:190–7. doi: 10.1207/s15327914nc5002_9 Knasmüller S Cavin C Chakraborty A Darroudi F Majer BJ Huber WW Ehrlich VA Structurally related mycotoxins ochratoxin A, ochratoxin B, and citrinin differ in their genotoxic activities and in their mode of action in human-derived liver (HepG2) cells: implications for risk assessment Nutr Cancer 200450190 7 10.1207/s15327914nc5002_915623466Abierto DOISearch in Google Scholar

Jia Y, Liu Z, Wang C, Meng Q, Huo X, Liu Q, Sun H, Sun P, Yang X, Ma X, Liu K. P-gp, MRP2, OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate. Toxicol Appl Pharmacol 2016:27–35. doi: 10.1016/j.taap.2016.06.030 Jia Y Liu Z Wang C Meng Q Huo X Liu Q Sun H Sun P Yang X Ma X Liu K P-gp, MRP2, OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate Toxicol Appl Pharmacol 20162735 10.1016/j.taap.2016.06.03027377006Abierto DOISearch in Google Scholar

Shi YW, Wang CP, Liu L, Liu YL, Wang X, Hong Y, Li Z, Kong LD. Antihyperuricemic and nephroprotective effects of resveratrol and its analogues in hyperuricemic mice. Mol Nutr Food Res 2012;56:1433–44. doi: 10.1002/mnfr.201100828 Shi YW Wang CP Liu L Liu YL Wang X Hong Y Li Z Kong LD Antihyperuricemic and nephroprotective effects of resveratrol and its analogues in hyperuricemic mice Mol Nutr Food Res 201256143344 10.1002/mnfr.20110082822865646Abierto DOISearch in Google Scholar

Rašić D, Mladinić M, Želježić D, Pizent A, Stefanović S, Milićević D, Konjevoda P, Peraica M. Effects of combined treatment with ochratoxin A and citrinin on oxidative damage in kidneys and liver of rats. Toxicon 2018;146:99–105. doi: 10.1016/J.TOXICON.2018.03.002 Rašić D Mladinić M Želježić D Pizent A Stefanović S Milićević D Konjevoda P Peraica M Effects of combined treatment with ochratoxin A and citrinin on oxidative damage in kidneys and liver of rats Toxicon 201814699 105 10.1016/J.TOXICON.2018.03.002Abierto DOISearch in Google Scholar

Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes [displayed 16 February 2022]. Available at https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes [displayed 16 February 2022] Available at https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDFSearch in Google Scholar

Frenich AG, Romero-González R, Gómez-Pérez ML, Vidal JLM. Multi-mycotoxin analysis in eggs using a QuEChERS-based extraction procedure and ultra-high-pressure liquid chromatography coupled to triple quadrupole mass spectrometry. J Chromatogr A 2011;1218:4349–56. doi: 10.1016/j.chroma.2011.05.005 Frenich AG Romero-González R Gómez-Pérez ML Vidal JLM Multi-mycotoxin analysis in eggs using a QuEChERS-based extraction procedure and ultra-high-pressure liquid chromatography coupled to triple quadrupole mass spectrometry J Chromatogr A 20111218434956 10.1016/j.chroma.2011.05.005Abierto DOISearch in Google Scholar

Domijan A-M, Peraica M, Ferencić Z, Cuzić S, Fuchs R, Lucić A, Radić B. Ochratoxin A-induced apoptosis in rat kidney tissue. Arh Hig Rada Toksikol 2004;55:243–8. PMID: 15584550 Domijan A-M Peraica M Ferencić Z Cuzić S Fuchs R Lucić A Radić B Ochratoxin A-induced apoptosis in rat kidney tissue Arh Hig Rada Toksikol 200455243 8 PMID: 15584550Search in Google Scholar

Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H. Characterization of ochratoxin A transport by human organic anion transporters. Life Sci 2001;69:2123–35. doi: 10.1016/S0024-3205(01)01296-6 Jung KY Takeda M Kim DK Tojo A Narikawa S Yoo BS Hosoyamada M Cha SH Sekine T Endou H Characterization of ochratoxin A transport by human organic anion transporters Life Sci 2001692123 35 10.1016/S0024-3205(01)01296-6Abierto DOISearch in Google Scholar

Knecht A, Schwerdt G, Gekle M, Humpf H-U. Combinatory effects of citrinin and ochratoxin A in immortalized human proximal tubule cells. Mycotoxin Res 2005;21:176–81. doi: 10.1007/BF02959258 Knecht A Schwerdt G Gekle M Humpf H-U Combinatory effects of citrinin and ochratoxin A in immortalized human proximal tubule cells Mycotoxin Res 200521176 81 10.1007/BF02959258Abierto DOISearch in Google Scholar

Karaica D, Micek V, Rašić D, Peraica M, Šegvić Klarić M, Breljak D. Subchronic exposure to individual and combined ochratoxin A and citrinin affects the expression of rat renal organic anion transporters. Mycotoxin Res 2020;36:339–52. doi: 10.1007/s12550-020-00399-4 Karaica D Micek V Rašić D Peraica M Šegvić Klarić M Breljak D Subchronic exposure to individual and combined ochratoxin A and citrinin affects the expression of rat renal organic anion transporters Mycotoxin Res 202036339 52 10.1007/s12550-020-00399-4Abierto DOISearch in Google Scholar

Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H. Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta 2002;1590:64–75. doi: 10.1016/S0167-4889(02)00187-8 Babu E Takeda M Narikawa S Kobayashi Y Enomoto A Tojo A Cha SH Sekine T Sakthisekaran D Endou H Role of human organic anion transporter 4 in the transport of ochratoxin A Biochim Biophys Acta 2002159064 75 10.1016/S0167-4889(02)00187-8Abierto DOISearch in Google Scholar

Riha J, Brenner S, Böhmdorfer M, Giessrigl B, Pignitter M, Schueller K, Thalhammer T, Stieger B, Somoza V, Szekeres T, Jäger W. Resveratrol and its major sulfated conjugates are substrates of organic anion transporting polypeptides (OATPs): Impact on growth of ZR-75-1 breast cancer cells. Mol Nutr Food Res 2014;58:1830–42. doi: 10.1002/mnfr.201400095 Riha J Brenner S Böhmdorfer M Giessrigl B Pignitter M Schueller K Thalhammer T Stieger B Somoza V Szekeres T Jäger W Resveratrol and its major sulfated conjugates are substrates of organic anion transporting polypeptides (OATPs): Impact on growth of ZR-75-1 breast cancer cells Mol Nutr Food Res 2014581830 42 10.1002/mnfr.20140009524996158Abierto DOISearch in Google Scholar

Jia Y, Liu Z, Wang C, Meng Q, Huo X, Liu Q, Sun H, Sun P, Yang X, Ma X, Liu K. P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate. Toxicol Appl Pharmacol 2016;306:27–35. doi: 10.1016/j.taap.2016.06.030 Jia Y Liu Z Wang C Meng Q Huo X Liu Q Sun H Sun P Yang X Ma X Liu K P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate Toxicol Appl Pharmacol 201630627 35 10.1016/j.taap.2016.06.03027377006Abierto DOISearch in Google Scholar

Artículos recomendados de Trend MD

Planifique su conferencia remota con Sciendo