Group28_Part1_ResearchProposal. Queens University PHAR 380
Research proposal Part 1: Background and Research Question
Group 28
Article: Benkerroum, N. (2020). Chronic and acute toxicities of aflatoxins: mechanisms of
action. International Journal of Environmental Research and Public Health, 17, 423.
https://doi.org/10.3390/ijerph17020423
1) Background:
Toxicokinetics:
The toxicokinetic
...[Show More]
Group28_Part1_ResearchProposal. Queens University PHAR 380
Research proposal Part 1: Background and Research Question
Group 28
Article: Benkerroum, N. (2020). Chronic and acute toxicities of aflatoxins: mechanisms of
action. International Journal of Environmental Research and Public Health, 17, 423.
https://doi.org/10.3390/ijerph17020423
1) Background:
Toxicokinetics:
The toxicokinetics of aflatoxins in humans can be described as following two metabolic
pathways. The most common entry route of aflatoxins to the body is through ingestion of the
strains of mold Aspergillus flavus and A. parasiticus which produce aflatoxin B1 (AFB1) and
aflatoxin B2 (AFB2). Following entry to the body, AFB1 can be absorbed in the duodenum and
later taken up by the liver. The microsomal mixed-function oxidase (MFO) enzymes bioactivate
the toxin to produce AFB1-exo-8,9 epoxide which is classified as a reactive epoxide
intermediate. This MFO is part of the CYP450 enzyme superfamily which is well known for its
metabolic effects on most drugs that enter the body. The presence of the epoxide intermediate is
usually what causes DNA mutations and disruption to RNA and protein formation which can
then lead to harmful outcomes. The second pathway that is known for the toxicokinetics of
aflatoxins is the biotransformation of AFB1 by hydroxylation. This pathway has been found to
produce a less toxic metabolite. AFB1 can also produce a dialdehyde form which is called
aflatoxin dialdehyde and this form can be excreted through urine if it interacts with aflatoxin
aldehyde reductase (AFAR). However, it is still able to bind to proteins like albumin (1)
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