Aflatoxicosis B1 (AFB1) is considered to possess the highest toxicity among various types of secondary metabolites produced by a larger number of Aspergillus spp, and classified as a Group I carcinogen for humans by the International Agency for Research on Cancer.
Many foods such as grains (corn, sorghum, and millet), peanuts, beans, and nuts (almonds, pistachios, etc.) may support the growth of Aspergillus, and may be contaminated with aflatoxins. AFB1 induces growth retardation, hepatocellular carcinoma, and immunosuppression.
Metabolism of AFB1 in the body:
AFB1 is metabolized by cytochrome P450 (CYP 450) enzyme systems after being absorbed in the intestinal tract. Subsequently, under the action of CYP 450, including cytochrome P450 (CYP 450) 1A2 .
CYP 3A4, AFB1 is transformed to exo-AFB1-8,9-epoxide (AFBO), which binds to DNA, proteins, and other critical cellular macromolecules to exert its carcinogenic effect.
However, AFB1 can be converted to aflatoxin Q1 (AFQ1) by CYP 3A4, or aflatoxin M1 (AFM1) by CYP 1A2, which is considered as one way of detoxification.
Glutathione conjugation can eliminate AFBO through the catalytic action of glutathione S-transferase (GST), which is activated by Nrf2-Antioxidant Response Element (ARE) response. Furthermore, GST A3 appeared to be the critical factor involved in AFB1 detoxification.
Mechanism of detoxification of AFB1 by Lactobacillus plantarum:
Lactobacillus plantarum (L. Plantarum) detoxify the AFB1 by following ways.
- Plantarum binds with the AFB1 in the intestine and this binding is not affected by the intestinal pH or the high levels of bile salts in the intestine. By binding with L. plantarum AFB1 is removed with feces along with the bile. In this way bioavailability of AFB1 in the blood decreases which results in reduced pathological changes in the body.
- Plantarum supplementation in diet improves the activities of antioxidant enzymes and decreases the lipid peroxidation in the serum and liver. Antioxidant enzymes play significant role in decreasing the toxic effects of AFB1
- The Addition of Plantarum in the diet decreases the expression level of CYP 1A2 and CYP 3A4 due to this the concentration of AFBO decreases that results in decreased pathological effects in the body.
- Plantarum increases the GST level which causes the detoxification of AFB1 as GST increases the conjugation of AFBO with the GSH to form a water soluble AFB1-GSH which is removed from the body with bile or urine.
- Interleukin-22 production from the natural killer cells increases by using Plantarum in the diet that increases the integrity of intestinal cells which results in decreased absorption of AFB1 from the intestinal tract.
L. plantarum can increase fecal AFB1excretion, reduce lipid peroxidation, and reverse deficits in antioxidant defense systems to alleviate AFB1 L. plantarum might play a role in the suppression of CYP 1A2 and CYP 3A4 expression to decrease the production of AFBO and activate GST A3 through Nrf2 signaling pathways to improve glutathione-conjugating activity and hence induce detoxification.
Authors: Ashiq Ali*1, Aisha Khatoon1, Zain- Ul- Abidin2, Muhammad Kashif Saleemi1.
1 Department of Pathology, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan.
2 Veterinary Research Institute, Lahore, Pakistan.
* Corresponding Author Email: firstname.lastname@example.org