Aflatoxins general account, types & importance

Aflatoxins-general account,types & importance.

1. Aflatoxins - General account, types & importance Vaishali S.Patil Professor, Department of Botany Shri Shivaji College of Arts, Commerce & Science Akola

2. Introduction Aflatoxins  are poisonous carcinogens and mutagens that are produced by 20 related fungal metabolites of certain  molds  ( Aspergillus flavus  and  Aspergillus parasiticus ) which grow in soil, decaying vegetation, hay, and grains. The molds can colonize and contaminate food before harvest or during storage, especially following prolonged exposure to a high-humidity environment, or to stressful conditions such as drought.  They are regularly found in improperly stored staple commodities such as cassava,  chili peppers, cottonseed, millet, peanuts, rice, sesame seeds, sorghum, sunflower seeds,  sweetcorn , tree nuts, wheat, and a variety of spices. Aflatoxin transformation products are sometimes found in eggs, milk products, and meat when animals are fed contaminated grains.  They have been found in both pet and human foods, as well as in feedstocks for agricultural animals. 

3. The aflatoxins were initially isolated and identified as the causative agent in Turkey X disease that caused necrosis of the liver in 1960 and over 100,000 turkeys died in England and USA and the death was attributed to the consumption of a mould-contaminated peanut meal. . Aflatoxins are highly liposoluble compounds and are readily absorbed from the site of exposure usually through the gastrointestinal tract and respiratory tract into blood stream. Human and animals get exposed to aflatoxins by two major routes (a) direct ingestion of aflatoxin -contaminated foods or ingestion of aflatoxins carried over from feed into milk and milk products like cheese and powdered milk as well as other animal tissues mainly as AFM 1 (b) by inhalation of dust particles of aflatoxins especially AFB 1  in contaminated foods in industries and factories. 

4. Aflatoxins produce by Aspergillus sp .

5. Types 1.Aflatoxin B 1  and B 2  (AFB), produced by  Aspergillus flavus  and  A. parasiticus 2.Aflatoxin G 1  and G 2  (AFG), produced by some Group II   A. flavus  and  Aspergillus parasiticus . 3.Aflatoxin M 1  (AFM 1 ), metabolite of aflatoxin B 1  in humans and animals (exposure in  ng  levels may come from a mother's milk) 4.Aflatoxin M 2 , metabolite of aflatoxin B 2  in milk of cattle fed on contaminated foods. 5. Aflatoxicol (AFL): metabolite produced by breaking down the lactone ring 6. Aflatoxin Q 1  (AFQ 1 ), major metabolite of AFB 1  in  in vitro  liver preparations of other higher vertebrates .

6. 1.Aflatoxin B 1 Chemical formula: C 17 H 12 O 6  is an  aflatoxin  produced by  Aspergillus flavus  and  A. parasiticus . It is a very potent  carcinogen  with a TD 50  3.2 μg /kg/day in rats. Aflatoxin B 1  is a common contaminant in a variety of foods including peanuts, cottonseed meal, corn, and other grains; as well as animal feeds. It is considered the most toxic aflatoxin and it is highly implicated in  hepatocellular carcinoma (HCC) in humans. In animals, aflatoxin B 1  has also been shown to be mutagenic,  teratogenic , and to cause  immunosuppression .  Several sampling and analytical methods including thin-layer chromatography (TLC), high-performance liquId chromatography (HPLC), mass spectrometry, and enzyme-linked immunosorbent assay (ELISA), among others, have been used to test for aflatoxin B 1  contamination in foods. Sources  - found in contaminated food and humans are exposed to aflatoxin B 1  almost entirely through their diet in swine and poultry production.

7. Pathology Reduction in weight of liver, vacuolation of  hepatocytes , and hepatic carcinoma.  Other liver lesions include enlargement of hepatic cells, fatty infiltration, necrosis,  hemorrhage , fibrosis, regeneration of nodules, and bile duct proliferation/hyperplasia. Toxicity 1.Acute toxicity s ymptoms include anorexia, malaise, and low-grade fever. 2.Subacute toxicity showed moderate to severe liver damage. 3. Chronic toxicity showed decreased hepatic microsomal cytochrome P-450 concentration, reduction in feed consumption and decreased weight gain. 4.Subchronic toxicity i n fish showed fish to present with preneoplastic lesions, concurrently with changes in gill, pancreas, intestine and spleen. 5.Genotoxicity DNA adducts, 8-hydroxyguanine lesions and DNA damage. 6. Carcinogenicity  the development of liver cell carcinoma. 7. Embryotoxicity development of the bursa of Fabricius .

8. 8.Teratogenicity reduced fetal weights, wrist drop, enlarged eye socket, agenesis of caudal vertebrae,  micropthalmia , cardiac defects, and lenticular degeneration. 9. Immunotoxicity reduced serum total globulin and reduced bactericidal activities. 2.Aflatoxin B2:  Molecular Formula: C 17 H 14 O 6 Moderately potent hepatotoxic , hepatocarcinogenic , mutagenic and teratogenic mycotoxins produced by  Aspergillus flavus   and  parasiticus .  Dihydroxy derivatives of aflatoxin B1. Formed during growth on the same commodities as aflatoxin B1 (including peanuts, corn and other cereals, and oilseeds), but in smaller amounts. Metabolized to aflatoxin M2, and excreted in milk in this form. 3.Aflatoxin G1- Molecular Formula:C 17 H 12 O 7 - Aflatoxin G1 is a toxic metabolite of the fungi Aspergillus flavus and A. Parasiticus . Aflatoxin G1 belongs to the class of organic compounds known as difurocoumarolactones .  Aflatoxin g is formally rated as a carcinogen (by IARC 1) and is also a potentially toxic compound. Aflatoxins are complex ring compounds that are fatal in large doses; in small doses they

9. induce tumors of the liver. Carcinogens, Mutagens, Teratogens . Skin, Eye, and Respiratory Irritations. 4.Aflatoxin G2 Molecular Formula:C 17 H 14 O 7 . Aflatoxin g2 is a very light and fluffy crystalline solid. Exhibits green-blue fluorescence.  Aflatoxin G2 ... /is/ the 9,10-dihydro derivative of  aflatoxin G1. 5.Aflatoxin M1.- It is a chemical compound of the  aflatoxin  class, a group of  mycotoxins  produced by three species of  Aspergillus  -  Aspergillus flavus ,  Aspergillus parasiticus , and the rare  Aspergillus nomius  - which contaminate plant and plant products. Aspergillus flavus  produces only B-type aflatoxins . Aflatoxin M 1  is the hydroxylated  metabolite of  aflatoxin B 1  and can be found in milk or milk products obtained from livestock that have ingested contaminated feed. Aflatoxin M 1  is usually considered to be a  detoxication  by-product of aflatoxin B 1 . The main sources of aflatoxins in feeds are peanut, meal, maize and cottonseed meal.

10.   The chemical structure of aflatoxin M 1 . Aflatoxin M 1  is the 4-hydroxy derivative of aflatoxin B 1  and is secreted in the milk of mammals that consume aflatoxin B 1 . Aflatoxin M 1  has a relative molecular mass of 328  Da  and has the molecular formula C 17 H 12 O 7 . Aflatoxin M 1  is found in milk, like human milk. Cows, sheep, goats and buffaloes that have consumed feeds contaminated with aflatoxin B 1 , aflatoxin M 1  will be formed as a result of the metabolic process in the livers of ruminants and excreted in milk. In other words, human beings can be exposed to the toxins through consumption of contaminated milk and other foods. Pathology The effect of aflatoxin M 1  was much weaker than aflatoxin B 1  in producing liver cancer. 6.Aflatoxin M2 Chemical FormulaC 17 H 14 O 7 produced by many species of Aspergillus , a fungus, most notably Aspergillus flavus and Aspergillus parasiticus . Aflatoxins are toxic and among the most carcinogenic substances known. Aflatoxin M2 is a metabolite of aflatoxin B2 in milk of cattle fed.

11.   . on contaminated foods. Aflatoxin M2 belongs to the family of Difurocoumarocyclopentenone Series. These are polycyclic aromatic compounds containing a cyclopenten-2-one ring fused to the coumarin moiety of the difurocoumarin skeleton. Difurocoumarocyclopentenones are a subgroup of the aflatoxins and related compounds. 7.Aflatoxicol (AFL):Molecular Formula:C 17 H 14 O 6 Increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism. 8. Aflatoxin Q1- Molecular Formula:C 17 H 12 O 7 Aflatoxin Q1 is a member of the class of aflatoxins that is  aflatoxin B1 in which the hydrogen at the pro-3S position is replaced by a  hydroxy  group. It has a role as a human xenobiotic metabolite and a carcinogenic agent. It is an aflatoxin , an aromatic ether and an aromatic ketone . It derives from an  aflatoxin B1.

12. Aflatoxin disease pathways in humans

13. Importance 1.High-level aflatoxin exposure produces an acute hepatic necrosis (acute aflatoxicosis ), resulting later in cirrhosis or carcinoma of the liver. Acute liver failure is made manifest by bleeding,  edema , alteration in digestion, changes to the absorption and/or metabolism of nutrients, and mental changes and/or coma. 2.Children are particularly affected by aflatoxin exposure, which is associated with stunted growth, delayed development, liver damage, and liver cancer.  3.After entering the body, aflatoxins may be metabolized by the liver to a reactive  epoxide  intermediate or hydroxylated to become the less harmful aflatoxin M 1 . 4. Aflatoxin metabolites may intercalate into DNA and  alkylate  the bases through epoxide  moiety. This is thought to cause mutations in the  p53  gene, an important gene in preventing cell cycle progression when there are DNA mutations, or signaling  apoptosis (programmed cell death).

14. 5.Effect of aflatoxins on mitochondrial DNA- damage the mitochondria can lead to mitochondrial diseases and may be responsible for aging mechanisms. The damage to mitDNA is caused by adduction and mutations of mitochondrial membranes leading to increased cell death (apoptosis) as well as disruption of energy production (production of ATP) . 6. Effect of aflatoxins on mitochondrial structure- AFB causes ultrastuctural changes in mitochondria and also induces mitochondrial directed apoptosis thus reducing their function. 7. Effect of aflatoxins on protein synthesis- reduction in protein content in body tissues like in skeletal muscle, heart, liver and kidney could be due to increased liver and kidney necrosis. 8.Aflatoxin B 1  can cause immune suppression, and exposure to it is associated with an increased viral load in HIV positive individuals. Prevention- A regular diet including apiaceous vegetables, such as carrots, parsnips, celery, and parsley may reduce the carcinogenic effects of aflatoxin .