Study · Molecules (Basel, Switzerland) · 2020Conflicts declared

Computer predictions of BHT's protein targets in the body

What it found

Computer modelling predicted that BHT can bind to several human proteins, including ones in the brain and gut.

The work was done in computers, not in people or animals.

What they found

Predicted protein targets

The computer analysis predicted that BHT can bind to the GABA-A receptor, serotonin 2B and 2C receptors, COX-1, and the noradrenaline transporter. These proteins are involved in brain signalling, inflammation, and stress responses.

Brain access

A computer prediction suggested that BHT can be taken in through the gut and can cross the blood-brain barrier. This means it could reach targets in the brain.

Binding to brain receptors

Docking models showed BHT binding to the same pockets on GABA-A and serotonin receptors as propofol, a sedative. The authors suggest this could affect brain circuits and lead to side effects like anxiety.

Binding to COX-1

BHT was predicted to bind to COX-1 in a similar way to flurbiprofen, an anti-inflammatory drug. This suggests BHT might affect inflammation, but the authors note this target is low confidence.

Binding to noradrenaline transporter

BHT was predicted to bind to the noradrenaline transporter and similar transporters, with a pattern like propofol. This could affect stress responses, but the authors say more experiments are needed.

What the authors conclude

“According to the results of this work, side effects of BHT, such as anxiety [ 10 ] and reduced heart beating activity [ 48 ], could be caused by modulation of 5-HT 2C , GABA-AR, NET and DAT, in the central nervous system.”
Tortosa V, Pietropaolo V, Brandi V, Macari G, Pasquadibisceglie A, Polticelli F, 2020

Also in their conclusions

  • They conclude that side effects of BHT, such as anxiety and reduced heart beating activity, could be caused by its effects on serotonin 2C, GABA-A, noradrenaline and dopamine transporters in the central nervous system.
  • They state that these conclusions must be taken with caution because the virtual screening analysis did not show a clear link between the computer scores and actual binding strength.
  • They advise that further experimental analyses are certainly required to support these findings.

How it was done

The authors wanted to explore possible reasons for BHT's toxic effects, since there is a lack of experimental studies on this additive.

They used computer tools to predict which human proteins BHT might interact with, then used molecular docking to model how BHT binds to four of those proteins. They compared BHT's binding to that of propofol, a similar compound.

What it can’t tell you

  • This study used only computer predictions and did not test BHT in people, animals, or cells.
  • The computer models cannot prove that BHT actually binds to these proteins in the body or that it causes any health effects.
  • The authors note that the docking scores did not correlate well with experimental binding data, so the predictions are uncertain.

The paper

Title
Computational Methods for the Identification of Molecular Targets of Toxic Food Additives. Butylated Hydroxytoluene as a Case Study
Type
Study
Summarised from
Full text
Cite
Tortosa V, Pietropaolo V, Brandi V, Macari G, Pasquadibisceglie A, Polticelli F (2020). Computational Methods for the Identification of Molecular Targets of Toxic Food Additives. Butylated Hydroxytoluene as a Case Study. Molecules (Basel, Switzerland). doi:10.3390/molecules25092229Free full textPubMed 32397407DOI

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