伏马菌素B1的毒性研究进展
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摘要
伏马菌素B1是国际癌症研究机构认定的2B类致癌物。伏马菌素B1是由串珠镰刀菌产生的毒性代谢产物,是一种真菌毒素,广泛分布于世界范围内的玉米中,严重危害人类健康,成为全球性公共卫生问题。文章综述了伏马菌素B1引起实验动物的各类毒性,包括肝毒性、肾毒性、遗传毒性、生殖发育毒性和致癌性,并对伏马菌素B1的代谢进行了概述,对其毒性机制进行了展望。
Fumonisin B1 has been identified as a 2 B carcinogen by International Agency for Research on Cancer. Fumonisin B1 is a kind of toxic metabolites produced mainly by fusarium moniliforme, which is a fungal toxin and commonly occurs on corn throughout the world. It is hazardous to human health and becomes a global public health problem. This paper reviews the toxicity to experimental animals induced by fumonisin B1, including hepatotoxicity, nephrotoxicity, genotoxicity, reproductive and developmental toxicity and carcinogenicity. And its metabolism is also reviewed. At the same time, this paper forecasts the toxic mechanism of fumonisin B1.
Fumonisin B1 has been identified as a 2 B carcinogen by International Agency for Research on Cancer. Fumonisin B1 is a kind of toxic metabolites produced mainly by fusarium moniliforme, which is a fungal toxin and commonly occurs on corn throughout the world. It is hazardous to human health and becomes a global public health problem. This paper reviews the toxicity to experimental animals induced by fumonisin B1, including hepatotoxicity, nephrotoxicity, genotoxicity, reproductive and developmental toxicity and carcinogenicity. And its metabolism is also reviewed. At the same time, this paper forecasts the toxic mechanism of fumonisin B1.
引文
[1]GELDERBLOM WCA,MARASAS WFO.Cancer promoting potential of different strains of Fusarium moniliforme in a short term cancer initiation promotion assay[J].Carcinogenesis,1988,9(8):1405-1409.
[2]MOSS MO.Recent studies of mycotoxins[J].Symposium,1998,27(27):62-76.
[3]GELDERBLOM WCA,JASKIEWICZ K,MARASAS WFO,et al.Fumonisin-novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme[J].Appl Environ Microbiol,1988,54(7):1806-1811.
[4]LAURENT D,PLATZER N,KOHLER F,et al.Macrofusin and micromonilin:two new mycotoxins isolated from corn infested by Fusarrium moniliforme[J/OL].Microbiol Aliment Nutr,1989,7:9-16.[2017-11-08].http://www.documentation.ird.fr/hor/fdi:43682.oai:ird.fr:fdi:43682.
[5]NORRED WP,PLATTNER RD,CHAMBERLAIN WJ.Distribution and excretion of[14C]fumonisin B1 in male Sprague-Dawley rats[J].Nat Toxins,1993,1(6):341-346.
[6]SHEPHARD GS,THIEL PG,SYDENHAM EW,et al.Biliary excretion of the mycotoxin fumonisin B1 in rats[J].Food Chem Toxicol,1994,32(5):489-491
[7]VOSS KA,CHAMBERLAIN WJ,BACON CW,et al.Subchronic toxicity of fumonisin B1 to male and female rats[J].Food Addit Contam,1995,12(3):473-478.
[8]BHANDARI N,HE Q,SHARMA RP.Gender-related differences in subacute fumonisin B1 hepatotoxicity in BALB/c mice[J].Toxicology,2001,165(2):195-204.
[9]BHANDARI N,BROWN CC,SHARMA RP.Fumonisin B1-induced localized activation of cytokine network in mouse liver[J].Food Chem Toxicol,2002,40(10):1483-1491.
[10]BHANDARI N,RAGHUBIR P,SHARMA.Modulation of selected cell signaling genes in mouse liver by fumonisin B1[J].Chem-Biol Interact,2002,139(3):317-331.
[11]SUZUKI CA,HIERLIHY L,BARKER M,et al.The Effects of Fumonisin B1 on Several Markers of Nephrotoxicity in Rats[J].Toxicol Appl Pharm,1995,133(2):207-214.
[12]ARANDA M,PEREZ-ALZOLA LM,SEPULVEDA C,et al.Assessment of in vitro mutagenicity in Salmonella and in vivo genotoxicity in mice of the mycotoxin fumonisin B1[J].Mutagenesis,2000,15(6):469-471.
[13]GELDERBLOM WCA,SNYMAN SD.Mutagenicity of potentially carcinogenic mycotoxins produced by Fusarium moniliforme[J].Mycotoxin Res,1991,7(2):46-52.
[14]EHRLICH V,DARROUDI F,UHL M,et al.Fumonisin B(1)is genotoxic in human derived hepatoma(Hep G2)cells[J].Mutagenesis,2002,17(3):257-260.
[15]GALVANO F,CAMPISI A,RUSSO A,et al.DNA Damage in Astrocytes Exposed to Fumonisin B1[J].Neurochem Res,2002,27(4):345-351.
[16]GALVANO F,RUSSO A,CARDILE V,et al.DNA damage in human fibroblasts exposed to fumonisin B(1)[J].Food Chem Toxicol,2002,40(1):25-31.
[17]THEUMER MG,C魣NEPA MC,L魷PEZ AG,et al.Subchronic mycotoxicoses in Wistar rats:assessment of the in vivo and in vitro genotoxicity induced by fumonisins and aflatoxin B(1),and oxidative stress biomarkers status[J].Toxicology,2010,268(1-2):104-110.
[18]VOSS KA,BACON CW,NORRED WP,et al.Studies on the reproductive effects of Fusarium moniliforme culture material in rats and the biodistribution of[14C]fumonisin B1 in pregnant rats[J].Nat Toxins,1996,4(1):24-33.
[19]GROSS SM,REDDY RV,ROTTINGHAUS GE,et al.Developmental effects of fumonisin B1-containing Fusarium moniliforme culture extract in CD1 mice[J].Mycopathologia,1994,128(2):111-118.
[20]REDDY RV,JOHNSON G,ROTTINGHAUS GE,et al.Developmental effects of fumonisin B1 in mice[J].Mycopathologia,1996,134(3):161-166.
[21]LABORDE JB,TERRY KK,HOWARD PC,et al.Lack of embryotoxicity of fumonisin B1 in New Zealand white rabbits[J].Fundam Appl Toxicol,1997,40(1):120-128.
[22]GELDERBLOM WC,KRIEK NP,MARASAS WF,et al.Toxicity and carcinogenicity of the Fusarium moniliforme metabolite,fumonisin B1,in rats[J].Carcinogenesis,1991,12(7):1247-1251.
[23]HOWARD PC,EPPLEY RM,STACK ME,et al.Fumonisin B1Carcinogenicity in a Two-Year Feeding Study Using F344 Rats and B6 C3 F1Mice[J].Environ Health Persp,2001,109(Suppl 2):277-282.
[24]HOWARD PC,WARBRITTON A,VOSS KA,et al.Compensatory regeneration as a mechanism for renal tubule carcinogenesis of fumonisin B1 in the F344/N/Nctr BR rat.[J].Environ Health Persp,2001,109(Suppl 2):309.
[25]VOSS KA,HOWARD PC,RILEY RT,et al.Carcinogenicity and mechanism of action of fumonisin B1:a mycotoxin produced by Fusarium moniliforme(=F.verticillioides)[J].Cancer Detect Prev,2002,26(1):1-9.
[26]MERRILL AH,SULLARDS MC,WANG E,et al.Sphingolipid metabolism:roles in signal transduction and disruption by fumonisins[J].Environ Health Persp,2001,109(2):283-289.
[27]R譩GNIER M,GOURBEYRE P,PINTON P,et al.Identification of Signaling Pathways Targeted by the Food Contaminant FB1:Transcriptome and Kinome Analysis of Samples from Pig Liver and Intestine[J].Mol Nutr Food Res,2017,12(5):e0178368.
[28]SINGH MP,KANG SC.Endoplasmic reticulum stress-mediated autophagy activation attenuates fumonisin B1 induced hepatotoxicity in vitro and in vivo[J/OL].Food Chem Toxicol,2017,110:371-382.[2017-12-20].https://www.sciencedirect.com/science/article/pii/S027869151730652X?via%3Dihub.DOI:10.1016/j.fct.2017.10.054.
[29]DEMIREL G,ALPERTUNGA B,OZDEN S.Role of fumonisin B1 on DNA methylation changes in rat kidney and liver cells[J].Pharm Biol,2015,53(9):1302-1310.
[30]HOVE M,POUCKE CV,NJUMBE-EDIAGE E,et al.Review on the natural co-occurrence of AFB1 and FB1 in maize and the combined toxicity of AFB1 and FB1[J/OL].Food Control,2016,59:675-682.[2018-01-01].http://xueshu.baidu.com/s?wd=paperuri%3A%2890da3993df99f6e1fffc3e73f4063421%29&filter=sc_long_sign&tn=SE_xue shusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS0956713515300815&ie=utf-8&sc_us=8145724460889732711.DOI:10.1016/j.foodcont.2015.06.053.
[31]CLARKE R,CONNOLLY L,FRIZZELL C,et al.Cytotoxic assessment of the regulated,co-existing mycotoxins aflatoxin B1,fumonisin B1 and ochratoxin,in single,binary and tertiary mixtures[J].Toxicon,2014,90:70-81.
[32]DU M,LIU Y,ZHANG G.Interaction of Aflatoxin B 1 and Fumonisin B 1 in Hep G2 Cell Apoptosis[J/OL].Food Bioscience,2017,20.[2018-4-9].https://www.sciencedirect.com/science/article/abs/pii/S2212429217301025.DOI:10.1016/j.fbio.2017.09.003.
[33]WEI Z,ZHANG S,ZHANG M,et al.Individual and combined effects of Fusarium,toxins on apoptosis in PK15 cells and the protective role of N-acetylcysteine[J/OL].Food Chem Toxicol,2018,111:27-43.[2017-4-9].http://xueshu.baidu.com/s?wd=paperuri%3A%2894 54623794b4f69c35e0ffce4ff94735%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS0278691517306555&ie=utf-8&sc_us=1790262488136712497.DOI:10.1016/j.fct.2017.10.057.
[34]QIAN GQ,TANG LL,LIN SH,et al.Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction[J/OL].Food Chem Toxicol,2016,95:188-195.[2017-4-9].http://xueshu.baidu.com/s?wd=paperuri%3A%28aed7a7b2bafa14dc97f8cc797139ce13%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS027869151630237X&ie=utf-8&sc_us=214973756711981993.DOI:10.1016/j.fct.2016.07.017.
[35]XUE KS,QIAN G,LIN S,et al.Modulation of pre-neoplastic biomarkers induced by sequential aflatoxin B 1,and fumonisin B 1,exposure in F344 rats treated with UPSN clay[J/OL].Food Chem Toxicol,2018,114.[2018-04-09].https://www.sciencedirect.com/science/article/pii/S0278691518301224.DOI:10.1016/j.fct.2018.02.048.
[36]YIN S,GUO X,LI J,et al.Fumonisin B1 induces autophagic cell death via activation of ERN1-MAPK8/9/10 pathway in monkey kidney MARC-145 cells.[J].Arch Toxicol,2016,90(4):985-996.
[37]DENLI M,BLANDON JC,SALADO S,et al.Efficacy of Adi Detox TM in reducing the toxicity of fumonisin B1 in rats[J/OL].Food Chem Toxicol,2015,78:60-63.[2018-04-09].http://xueshu.baidu.com/s?wd=paperuri%3A%28b6458608a362e06025aa3c0cd7ef093f%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2Fs027869151500037x&ie=utf-8&sc_us=17132529362584106345.DOI:10.1016/j.fct.2015.01.024.
[38]ZADEH MH,SHAHDADI H.Nanocellulose coated with various free fatty acids can adsorb fumonisin B1,and decrease its toxicity[J/OL].Colloid Surface B,2015,134:26-30.[2018-04-09].http://xueshu.baidu.com/s?wd=paperuri%3A%28e0df31ed6e052625ad9e9a1b218df3cb%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS092777651500421X&ie=utf-8&sc_us=4288781987273523347.DOI:10.1016/j.colsurfb.2015.06.037.
[2]MOSS MO.Recent studies of mycotoxins[J].Symposium,1998,27(27):62-76.
[3]GELDERBLOM WCA,JASKIEWICZ K,MARASAS WFO,et al.Fumonisin-novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme[J].Appl Environ Microbiol,1988,54(7):1806-1811.
[4]LAURENT D,PLATZER N,KOHLER F,et al.Macrofusin and micromonilin:two new mycotoxins isolated from corn infested by Fusarrium moniliforme[J/OL].Microbiol Aliment Nutr,1989,7:9-16.[2017-11-08].http://www.documentation.ird.fr/hor/fdi:43682.oai:ird.fr:fdi:43682.
[5]NORRED WP,PLATTNER RD,CHAMBERLAIN WJ.Distribution and excretion of[14C]fumonisin B1 in male Sprague-Dawley rats[J].Nat Toxins,1993,1(6):341-346.
[6]SHEPHARD GS,THIEL PG,SYDENHAM EW,et al.Biliary excretion of the mycotoxin fumonisin B1 in rats[J].Food Chem Toxicol,1994,32(5):489-491
[7]VOSS KA,CHAMBERLAIN WJ,BACON CW,et al.Subchronic toxicity of fumonisin B1 to male and female rats[J].Food Addit Contam,1995,12(3):473-478.
[8]BHANDARI N,HE Q,SHARMA RP.Gender-related differences in subacute fumonisin B1 hepatotoxicity in BALB/c mice[J].Toxicology,2001,165(2):195-204.
[9]BHANDARI N,BROWN CC,SHARMA RP.Fumonisin B1-induced localized activation of cytokine network in mouse liver[J].Food Chem Toxicol,2002,40(10):1483-1491.
[10]BHANDARI N,RAGHUBIR P,SHARMA.Modulation of selected cell signaling genes in mouse liver by fumonisin B1[J].Chem-Biol Interact,2002,139(3):317-331.
[11]SUZUKI CA,HIERLIHY L,BARKER M,et al.The Effects of Fumonisin B1 on Several Markers of Nephrotoxicity in Rats[J].Toxicol Appl Pharm,1995,133(2):207-214.
[12]ARANDA M,PEREZ-ALZOLA LM,SEPULVEDA C,et al.Assessment of in vitro mutagenicity in Salmonella and in vivo genotoxicity in mice of the mycotoxin fumonisin B1[J].Mutagenesis,2000,15(6):469-471.
[13]GELDERBLOM WCA,SNYMAN SD.Mutagenicity of potentially carcinogenic mycotoxins produced by Fusarium moniliforme[J].Mycotoxin Res,1991,7(2):46-52.
[14]EHRLICH V,DARROUDI F,UHL M,et al.Fumonisin B(1)is genotoxic in human derived hepatoma(Hep G2)cells[J].Mutagenesis,2002,17(3):257-260.
[15]GALVANO F,CAMPISI A,RUSSO A,et al.DNA Damage in Astrocytes Exposed to Fumonisin B1[J].Neurochem Res,2002,27(4):345-351.
[16]GALVANO F,RUSSO A,CARDILE V,et al.DNA damage in human fibroblasts exposed to fumonisin B(1)[J].Food Chem Toxicol,2002,40(1):25-31.
[17]THEUMER MG,C魣NEPA MC,L魷PEZ AG,et al.Subchronic mycotoxicoses in Wistar rats:assessment of the in vivo and in vitro genotoxicity induced by fumonisins and aflatoxin B(1),and oxidative stress biomarkers status[J].Toxicology,2010,268(1-2):104-110.
[18]VOSS KA,BACON CW,NORRED WP,et al.Studies on the reproductive effects of Fusarium moniliforme culture material in rats and the biodistribution of[14C]fumonisin B1 in pregnant rats[J].Nat Toxins,1996,4(1):24-33.
[19]GROSS SM,REDDY RV,ROTTINGHAUS GE,et al.Developmental effects of fumonisin B1-containing Fusarium moniliforme culture extract in CD1 mice[J].Mycopathologia,1994,128(2):111-118.
[20]REDDY RV,JOHNSON G,ROTTINGHAUS GE,et al.Developmental effects of fumonisin B1 in mice[J].Mycopathologia,1996,134(3):161-166.
[21]LABORDE JB,TERRY KK,HOWARD PC,et al.Lack of embryotoxicity of fumonisin B1 in New Zealand white rabbits[J].Fundam Appl Toxicol,1997,40(1):120-128.
[22]GELDERBLOM WC,KRIEK NP,MARASAS WF,et al.Toxicity and carcinogenicity of the Fusarium moniliforme metabolite,fumonisin B1,in rats[J].Carcinogenesis,1991,12(7):1247-1251.
[23]HOWARD PC,EPPLEY RM,STACK ME,et al.Fumonisin B1Carcinogenicity in a Two-Year Feeding Study Using F344 Rats and B6 C3 F1Mice[J].Environ Health Persp,2001,109(Suppl 2):277-282.
[24]HOWARD PC,WARBRITTON A,VOSS KA,et al.Compensatory regeneration as a mechanism for renal tubule carcinogenesis of fumonisin B1 in the F344/N/Nctr BR rat.[J].Environ Health Persp,2001,109(Suppl 2):309.
[25]VOSS KA,HOWARD PC,RILEY RT,et al.Carcinogenicity and mechanism of action of fumonisin B1:a mycotoxin produced by Fusarium moniliforme(=F.verticillioides)[J].Cancer Detect Prev,2002,26(1):1-9.
[26]MERRILL AH,SULLARDS MC,WANG E,et al.Sphingolipid metabolism:roles in signal transduction and disruption by fumonisins[J].Environ Health Persp,2001,109(2):283-289.
[27]R譩GNIER M,GOURBEYRE P,PINTON P,et al.Identification of Signaling Pathways Targeted by the Food Contaminant FB1:Transcriptome and Kinome Analysis of Samples from Pig Liver and Intestine[J].Mol Nutr Food Res,2017,12(5):e0178368.
[28]SINGH MP,KANG SC.Endoplasmic reticulum stress-mediated autophagy activation attenuates fumonisin B1 induced hepatotoxicity in vitro and in vivo[J/OL].Food Chem Toxicol,2017,110:371-382.[2017-12-20].https://www.sciencedirect.com/science/article/pii/S027869151730652X?via%3Dihub.DOI:10.1016/j.fct.2017.10.054.
[29]DEMIREL G,ALPERTUNGA B,OZDEN S.Role of fumonisin B1 on DNA methylation changes in rat kidney and liver cells[J].Pharm Biol,2015,53(9):1302-1310.
[30]HOVE M,POUCKE CV,NJUMBE-EDIAGE E,et al.Review on the natural co-occurrence of AFB1 and FB1 in maize and the combined toxicity of AFB1 and FB1[J/OL].Food Control,2016,59:675-682.[2018-01-01].http://xueshu.baidu.com/s?wd=paperuri%3A%2890da3993df99f6e1fffc3e73f4063421%29&filter=sc_long_sign&tn=SE_xue shusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS0956713515300815&ie=utf-8&sc_us=8145724460889732711.DOI:10.1016/j.foodcont.2015.06.053.
[31]CLARKE R,CONNOLLY L,FRIZZELL C,et al.Cytotoxic assessment of the regulated,co-existing mycotoxins aflatoxin B1,fumonisin B1 and ochratoxin,in single,binary and tertiary mixtures[J].Toxicon,2014,90:70-81.
[32]DU M,LIU Y,ZHANG G.Interaction of Aflatoxin B 1 and Fumonisin B 1 in Hep G2 Cell Apoptosis[J/OL].Food Bioscience,2017,20.[2018-4-9].https://www.sciencedirect.com/science/article/abs/pii/S2212429217301025.DOI:10.1016/j.fbio.2017.09.003.
[33]WEI Z,ZHANG S,ZHANG M,et al.Individual and combined effects of Fusarium,toxins on apoptosis in PK15 cells and the protective role of N-acetylcysteine[J/OL].Food Chem Toxicol,2018,111:27-43.[2017-4-9].http://xueshu.baidu.com/s?wd=paperuri%3A%2894 54623794b4f69c35e0ffce4ff94735%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS0278691517306555&ie=utf-8&sc_us=1790262488136712497.DOI:10.1016/j.fct.2017.10.057.
[34]QIAN GQ,TANG LL,LIN SH,et al.Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction[J/OL].Food Chem Toxicol,2016,95:188-195.[2017-4-9].http://xueshu.baidu.com/s?wd=paperuri%3A%28aed7a7b2bafa14dc97f8cc797139ce13%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS027869151630237X&ie=utf-8&sc_us=214973756711981993.DOI:10.1016/j.fct.2016.07.017.
[35]XUE KS,QIAN G,LIN S,et al.Modulation of pre-neoplastic biomarkers induced by sequential aflatoxin B 1,and fumonisin B 1,exposure in F344 rats treated with UPSN clay[J/OL].Food Chem Toxicol,2018,114.[2018-04-09].https://www.sciencedirect.com/science/article/pii/S0278691518301224.DOI:10.1016/j.fct.2018.02.048.
[36]YIN S,GUO X,LI J,et al.Fumonisin B1 induces autophagic cell death via activation of ERN1-MAPK8/9/10 pathway in monkey kidney MARC-145 cells.[J].Arch Toxicol,2016,90(4):985-996.
[37]DENLI M,BLANDON JC,SALADO S,et al.Efficacy of Adi Detox TM in reducing the toxicity of fumonisin B1 in rats[J/OL].Food Chem Toxicol,2015,78:60-63.[2018-04-09].http://xueshu.baidu.com/s?wd=paperuri%3A%28b6458608a362e06025aa3c0cd7ef093f%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2Fs027869151500037x&ie=utf-8&sc_us=17132529362584106345.DOI:10.1016/j.fct.2015.01.024.
[38]ZADEH MH,SHAHDADI H.Nanocellulose coated with various free fatty acids can adsorb fumonisin B1,and decrease its toxicity[J/OL].Colloid Surface B,2015,134:26-30.[2018-04-09].http://xueshu.baidu.com/s?wd=paperuri%3A%28e0df31ed6e052625ad9e9a1b218df3cb%29&filter=sc_long_sign&tn=SE_xueshusource_2kduw22v&sc_vurl=http%3A%2F%2Fwww.sciencedirect.com%2Fscience%2Farticle%2Fpii%2FS092777651500421X&ie=utf-8&sc_us=4288781987273523347.DOI:10.1016/j.colsurfb.2015.06.037.