Chemical profiling of smokeless tobacco and their disease association
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1
National Institute of Cancer Prevention and Research (NICPR), India
2
Indian Council of Medical Research, India
Publication date: 2018-03-01
Tob. Induc. Dis. 2018;16(Suppl 1):A27
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ABSTRACT
Background:
Smokeless
tobacco (SLT) products are consumed by millions of people in over 130 countries
around the world. SLT products have a large impact on the health of individuals
since the products cause several diseases including cancer. Though the
smokeless tobacco products have been found to be associated with a large number
of health effects and diseases, the understanding of the functions of chemical
compounds of the products and their toxicity is very limited. There is a
complete lack of extensive analysis of the targets of the chemical compounds
and their associated biological mechanisms remain unknown.
Methods:
One hundred and one chemical compounds of SLT
products were studied and similarity search algorithms were used to identify similar
compounds along with their protein targets using ChEMBL. The protein targets
were functionally annotated using PANTHER classification system and Kyoto
Encyclopedia of Genes and Genomes (KEGG) to identify the associated Gene
Ontologies and diseases respectively and the interaction network was studied.
In addition, pharmacological and toxicological
profiling ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) of chemicals were also studied.
Results:
The study shows that the chemical compounds from
SLT products target more than 350 human proteins involved in a plethora of
human biological processes and affect around 100 pathways. The study has
identified associations of diseases such as neurodegenerative, immune and
cardiac diseases which were not known previously along with already established
diseases such as cancer.
Conclusions:
We
provide the first comprehensive report and systematic analyses of 101 chemical
compounds from different SLT products used worldwide. The finding indicates
far-reaching impact of SLT products on human health than already known and this
finding needs further validations using epidemiological, in-vitro and in-vivo
methodologies.