Amoxicillin decreased KEAP1, CPT1, CHOP expression and PPARa transactivation

A post from another group about TS gave me additional insight: a child had strep infection and was treated with amoxicillin. Vocal and motor tics appeared.

I quickly researched if there is a connection between amoxicillin and NRF2 because NRF2 overactivation is the main suspect in my model of tics development.

This is what I found:

Amoxicillin decreased KEAP1 gene expression significantly (p < 0.01) and dose-dependently. Penicillin did not affect KEAP1 gene expression, whereas streptomycin and the combination of penicillin and streptomycin significantly (p < 0.05) decreased KEAP1 gene expression.

Moreover, amoxicillin significantly (p < 0.01) decreased CPT1 gene expression, whereas penicillin, streptomycin, and the combination of penicillin and streptomycin did not change CPT1 mRNA expression.

Furthermore, amoxicillin significantly (p < 0.05) decreased CHOP gene expression whereas penicillin, streptomycin, and the combination of penicillin and streptomycin did not change CHOP gene expression (Figure 2).

In line with the lowering effect on CPT1 mRNA expression, amoxicillin also significantly (p < 0.01) lowered PPARα transactivation." (R1)

Lowered amount of KEAP1 protein directly increases chances of NRF2 activation because KEAP1 is the main trap for Nrf2.

This antibiotic also interferes with fat metabolism by lowering carnitine transport and metabolic switching via PPARa.