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Aflatoxin G1
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Aflatoxin G1

Aflatoxins are highly toxic and carcinogenic metabolites produced by molds like Aspergillus flavus and Aspergillus parasiticus, which commonly contaminate foods such as peanuts, corn, and spices. 

Among these, aflatoxin G1 (AFG1) is particularly concerning due to its prevalence in cereals, legumes, dairy products, and non-alcoholic beers. 

Known for its nephrotoxic effects, AFG1 can cause significant kidney damage, as evidenced by decreased expression of aquaporin-1 and histopathological changes in renal tissues. 

Acute exposure to AFG1 can lead to severe toxicity, while chronic exposure increases the risk of liver cancer and immune suppression. 

AFG1’s stability and ability to bioaccumulate in the body, particularly in the liver, underscore the importance of monitoring and managing aflatoxin contamination in food supplies to safeguard public health.

What are Aflatoxins?  [8.] 

Aflatoxins are a group of highly toxic and carcinogenic compounds produced as secondary metabolites by certain molds, primarily Aspergillus flavus and Aspergillus parasiticus.  [8., 22.]

They are one type of mycotoxin, which are a larger group of toxic chemical compounds produced by molds.  

These mycotoxins are formed when the molds colonize foods like peanuts, corn, cottonseed, tree nuts, and spices under favorable temperature and humidity conditions.   [8., 20.] 

The main aflatoxins are B1, B2, G1, and G2, with aflatoxin B1 (AFB1) being the most potent and carcinogenic.  [3.] 

Their production occurs when the mold's growth is stressed, such as during drought conditions or improper crop storage. 

Aflatoxins are among the most carcinogenic substances known - they can cause acute toxicity leading to liver failure, hemorrhaging, and even death in severe cases.   [8.]  Chronic exposure increases the risk of developing liver cancer, as aflatoxins can bind to DNA and cause mutations, particularly in the p53 tumor suppressor gene. [8., 10.]

They can also suppress the immune system, and can cause stunted growth in children.  [9., 13., 14.] 

Worryingly, aflatoxins are highly stable and can persist in foods and animal feeds even after processing and cooking.  They bioaccumulate in the body over time, especially in the liver, due to their lipophilic nature and resistance to metabolic breakdown.  [1., 11., 12.] 

Aflatoxin B1 is metabolized to the reactive aflatoxin-8,9-epoxide, which binds to DNA and proteins, initiating carcinogenesis.  [14.] 

Animals fed contaminated feed can pass aflatoxin metabolites into meat, milk, and eggs, posing risks to humans consuming these products.

Anti-Aflatoxin Biomarkers

Anti-aflatoxin biomarkers are a group of compounds or metabolites that can be measured in biological samples to assess exposure to aflatoxins, which are toxic and carcinogenic metabolites produced by certain molds. 

These biomarkers provide a direct measure of internal exposure and can help evaluate the associated health risks.

A variety of biomarkers have been used to identify the presence of aflatoxins in humans and animals.  

Aflatoxin B1, known as one of the most potent and toxic aflatoxins, is one such biomarker. 

What is Aflatoxin G1?  [8., 11.]

Aflatoxin G1 (AFG1) is one of the major aflatoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus, along with aflatoxins B1, B2, and G2.

AFG1 is a difuranocoumarin derivative with a molecular formula of C17H12O7.  It is structurally similar to the highly potent aflatoxin B1, differing only in the position of a double bond in the terminal furan ring.  [7., 17.] 

Like other aflatoxins, AFG1 is a naturally occurring mycotoxin that can contaminate a wide range of foods including cereals, oilseeds, spices, and tree nuts like maize, peanuts, pistachios, chilies, and dried fruits.  It has also been detected in milk and milk products due to carry-over from contaminated animal feed.

AFG1 contamination can occur during the pre- and post-harvest stages of food production, especially under conditions of high temperature and humidity, which are favorable for fungal growth.

While less is known about the chronic toxicity of AFG1 compared to AFB1, it is also considered a potent carcinogen, though probably slightly less potent than AFB1.  The International Agency for Research on Cancer (IARC) has classified AFG1 as a Group 1 carcinogen, meaning it is carcinogenic to humans.  [8.] 

AFG1 can undergo metabolic activation in the liver, forming reactive epoxide intermediates that can bind to DNA and proteins, potentially leading to mutagenesis and carcinogenesis.  However, the specific metabolic pathways and DNA adducts formed by AFG1 may differ from those of AFB1.

AFG1 poses significant health risks due to its carcinogenic, mutagenic, teratogenic, and immunosuppressive properties.

Toxicity and Health Effects of Aflatoxin G1  [8., 16.]  

Acute and Chronic Toxicity  

Acute exposure to high levels of Aflatoxin G1 can lead to aflatoxicosis, characterized by symptoms such as vomiting, abdominal pain, hepatitis, and even death in severe cases.

Chronic exposure to lower levels of Aflatoxin G1 has been associated with impaired nutrient metabolism, immunosuppression, and liver disorders like cirrhosis and hepatocellular carcinoma.

Aflatoxin G1 Carcinogenic Potential  [8.]

Aflatoxin G1 is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), indicating its strong carcinogenic potential.  Long-term exposure to Aflatoxin G1 has been linked to an increased risk of liver cancer, particularly in regions with high aflatoxin exposure and hepatitis B virus prevalence.

Immunotoxicity  [24.]  

Aflatoxin G1 can suppress the immune system, making individuals more susceptible to infectious diseases.

Aflatoxin G1’s Effects on Renal Health  [19.] 

Aflatoxin G1 (AFG1) can exert detrimental effects on renal cells and overall renal health. 

Exposure to AFG1 has been shown to cause degenerative changes, necrosis, and destruction of renal tubular epithelial cells, as well as hyaline cast formation, glomerular atrophy, and dilation of urinary tracts in renal tissue.

AFG1 treatment leads to significant increases in serum urea and creatinine levels, indicating impaired renal function and altered protein metabolism, while also decreasing serum sodium and potassium levels, suggesting electrolyte imbalance and impaired excretion of waste products.

Furthermore, AFG1 exposure significantly reduces the expression of aquaporin-1, a water channel protein, in renal tissue, contributing to renal dysfunction and impaired water reabsorption. 

Collectively, these findings demonstrate the nephrotoxic effects of AFG1, inducing histopathological changes, altering renal biomarkers, and dysregulating aquaporin-1 expression, ultimately leading to renal damage and impaired renal health .

Aflatoxin G1 Laboratory Testing Methods

Test Information, Sample Collection and Preparation

Various biological samples can be employed to detect and quantify anti-aflatoxin biomarkers, particularly blood, urine and nasal secretions.

Blood samples are typically collected via venipuncture in a clinical setting, while urine and nasal secretion samples may be collected from the comfort of home.  

It is important to consult with the ordering provider prior to sample collection, as certain protocols may be recommended beforehand.  

Interpretation of Aflatoxin G1 Test Results

Optimal Levels of Aflatoxin G1 Test Results

Because of the high level of toxicity of aflatoxins, optimal test results indicate undetectable levels of aflatoxins.  

Clinical Significance of Elevated Aflatoxin G1

Elevated levels of aflatoxins indicate recent or current exposure to aflatoxins.  However, because they are known to bioaccumulate, testing positive for the presence of aflatoxins may indicate a persistent historical exposure.  [4., 13.] 

Clinical Significance of Low Aflatoxin G1

Low or undetectable levels of aflatoxins are considered ideal.  

Aflatoxin G1 Related Biomarkers

In addition to the direct measurement of anti-aflatoxin biomarkers, other biomarkers can provide complementary information about aflatoxin exposure and its potential health effects.

Oxidative Stress Markers  [14., 15.]

Aflatoxin exposure is known to induce oxidative stress, which can lead to cellular damage and contribute to the development of various diseases. 

Biomarkers such as malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) can be measured to assess oxidative stress levels and the associated risk of aflatoxin-related toxicity.  [15.] 

Liver Function Markers  [5.] 

Since the liver is a primary target organ for aflatoxin toxicity, monitoring liver function biomarkers like alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin can provide insights into the extent of hepatic injury and potential liver damage caused by aflatoxin exposure.  

Inflammatory Biomarkers  [15.] 

Aflatoxin exposure can trigger inflammatory responses, and biomarkers such as C-reactive protein (CRP), interleukins (e.g., IL-6, IL-8), and tumor necrosis factor-alpha (TNF-α) can be measured to evaluate the inflammatory status and associated health risks.

Aflatoxins B1, B2, and G2

Aflatoxins B1, B2, G1, and G2 are the four major aflatoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus.  Testing for all four provides a comprehensive assessment of aflatoxin contamination.

Aflatoxin B1 (AFB1) is considered the most potent and carcinogenic aflatoxin . It is crucial to test for AFB1 due to its severe toxicity and strong link to hepatocellular carcinoma (liver cancer).

While less potent than AFB1, aflatoxins G1 and B2 are also known carcinogens and can contribute to the overall toxicity of aflatoxin-contaminated food and feed products.  [9., 19.] 

Co-occurrence and co-exposure to multiple aflatoxins are common in various food commodities like cereals, nuts, and spices.  Testing for all four major aflatoxins provides a comprehensive assessment of the overall aflatoxin burden.

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See References

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[2.] Chen CH, Wang MH, Wang JH, et al. Aflatoxin Exposure and Hepatitis C Virus in Advanced Liver Disease in a Hepatitis C Virus–Endemic Area in Taiwan. American Journal of Tropical Medicine and Hygiene. 2007;77(4):747-752. doi:https://doi.org/10.4269/ajtmh.2007.77.747

[3.] Dai C, Tian E, Hao Z, Tang S, Wang Z, Sharma G, Jiang H, Shen J. Aflatoxin B1 Toxicity and Protective Effects of Curcumin: Molecular Mechanisms and Clinical Implications. Antioxidants (Basel). 2022 Oct 14;11(10):2031. doi: 10.3390/antiox11102031. PMID: 36290754; PMCID: PMC9598162.

[4.] Ferri F, Brera C, De Santis B, Collini G, Crespi E, Debegnach F, Gargano A, Gattei D, Magnani I, Mancuso P, Mozzanica S, Teodori E, Djuric O, Giorgi Rossi P. Association between Urinary Levels of Aflatoxin and Consumption of Food Linked to Maize or Cow Milk or Dairy Products. Int J Environ Res Public Health. 2020 Apr 6;17(7):2510. doi: 10.3390/ijerph17072510. PMID: 32268619; PMCID: PMC7177871.

[5.] Gong YY, Watson S, Routledge MN. Aflatoxin Exposure and Associated Human Health Effects, a Review of Epidemiological Studies. Food Safety. 2016;4(1):14-27. doi:https://doi.org/10.14252/foodsafetyfscj.2015026

[6.] Güç, İ., Yalçin, E., Çavuşoğlu, K. et al. Toxicity mechanisms of aflatoxin M1 assisted with molecular docking and the toxicity-limiting role of trans-resveratrol. Sci Rep 12, 14471 (2022). https://doi.org/10.1038/s41598-022-18791-8

[7.] Human Metabolome Database: Showing metabocard for Aflatoxin G (HMDB0030474). hmdb.ca. Accessed June 3, 2024. https://hmdb.ca/metabolites/HMDB0030474

[8.] International Agency For Research On Cancer. Working Group On The Evaluation Of The Carcinogenic Risks To Humans. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene : This Publication Represents the Views and Expert Opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Which Met in Lyon, 12-19 February 2002. Iarc; 2002.

[9.] Jiang Y, Jolly PE, Preko P, Wang JS, Ellis WO, Phillips TD, Williams JH. Aflatoxin-related immune dysfunction in health and in human immunodeficiency virus disease. Clin Dev Immunol. 2008;2008:790309. doi: 10.1155/2008/790309. PMID: 18695741; PMCID: PMC2496958.

[10.] Kew MC. Aflatoxins as a cause of hepatocellular carcinoma. J Gastrointestin Liver Dis. 2013 Sep;22(3):305-10. PMID: 24078988.

[11.] Kumar P, Mahato DK, Kamle M, Mohanta TK, Kang SG. Aflatoxins: A Global Concern for Food Safety, Human Health and Their Management. Front Microbiol. 2017 Jan 17;7:2170. doi: 10.3389/fmicb.2016.02170. PMID: 28144235; PMCID: PMC5240007.

[12.] MANCINI A, DREASSI E, BOTTA M, TARCHI F, FRANCARDI V. BIOACCUMULATION RISK ASSESSMENT OF AFLATOXIN B1, OCHRA-TOXIN AND FUMONISIN B1 IN TENEBRIO MOLITOR LARVAE. Redia. 2020;103:101-108. doi:https://doi.org/10.19263/redia-103.20.16

[13.] Mao Y, Dang M, Zhang J, et al. Peptide amphiphile inspired self-assembled, ordered gold nanocomposites for improved sensitivity of electrochemical immunosensor: Applications in determining the total aflatoxin amount in food stuffs. Talanta. 2022;247:123532-123532. doi:https://doi.org/10.1016/j.talanta.2022.123532

[14.] Mutocheluh M, Narkwa PW. Aflatoxin B1: An Immunomodulator and Cancer Agent. www.intechopen.com. Published November 30, 2022. https://www.intechopen.com/chapters/83715

[15.] Peng T, Li LQ, Peng MH, et al. Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1 a multi-center and multi-biomarker study. Carcinogenesis. 2007;28(11):2347-2354. doi:https://doi.org/10.1093/carcin/bgm193

[16.] Pickova D, Ostry V, Toman J, Malir F. Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation. Toxins (Basel). 2021 Jun 3;13(6):399. doi: 10.3390/toxins13060399. PMID: 34205163; PMCID: PMC8227755.

[17.] PubChem. Aflatoxin G1. pubchem.ncbi.nlm.nih.gov. https://pubchem.ncbi.nlm.nih.gov/compound/Aflatoxin-G1

[18.] Tong Y, Tonui P, Orang'o O, Zhang J, Maina T, Muthoka K, Groopman J, Smith J, Madeen E, Ermel A, Loehrer P, Brown D. Association of Plasma Aflatoxin With Persistent Detection of Oncogenic Human Papillomaviruses in Cervical Samples From Kenyan Women Enrolled in a Longitudinal Study. Res Sq [Preprint]. 2023 Jan 27:rs.3.rs-2468599. doi: 10.21203/rs.3.rs-2468599/v1. Update in: BMC Infect Dis. 2023 Jun 6;23(1):377. PMID: 36747756; PMCID: PMC9901024.

[19.] Touraj Zamir-Nasta, Ahmadi A, Moein Yazdkhasti, Pazhouhi M, Jalili C, Rezaei K. Effects of Exposure to Aflatoxin G1 on the Plasma Biochemical Factors and Histopathological Properties of Renal Tissue in Mice. Iranian journal of toxicology. 2021;15(2):127-134. doi:https://doi.org/10.32598/ijt.15.2.787.1

[20.] Turner PC, Snyder JA. Development and Limitations of Exposure Biomarkers to Dietary Contaminants Mycotoxins. Toxins (Basel). 2021 Apr 28;13(5):314. doi: 10.3390/toxins13050314. PMID: 33924868; PMCID: PMC8147022.

[21.] Wu X, Meng W, Duan C, et al. AFG1-induced TNF-α-mediated inflammation enhances gastric epithelial cell injury via CYP2E1. Food and chemical toxicology. 2023;176:113756-113756. doi:https://doi.org/10.1016/j.fct.2023.113756

[22.] Xu Y, Gong YY, Routledge MN. Aflatoxin exposure assessed by aflatoxin albumin adduct biomarker in populations from six African countries: REVIEW ARTICLE. World Mycotoxin J. 2018;11(3):411-419. doi: 10.3920/WMJ2017.2284. Epub 2018 Aug 1. PMID: 33552312; PMCID: PMC7797627.

[23.] Xue M, Fu M, Zhang M, et al. Aflatoxin B1 Induced Oxidative Stress and Gut Microbiota Disorder to Increase the Infection of Cyprinid Herpesvirus 2 in Gibel Carp (Carassius auratus gibelio). Antioxidants. 2023;12(2):306-306. doi:https://doi.org/10.3390/antiox12020306

[24.] Zhou X, Gan F, Hou L, et al. Aflatoxin B1 Induces Immunotoxicity through the DNA Methyltransferase-Mediated JAK2/STAT3 Pathway in 3D4/21 Cells. Journal of Agricultural and Food Chemistry. 2019;67(13):3772-3780. doi:https://doi.org/10.1021/acs.jafc.8b07309

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