Chloroquine commonly induces hormetic dose responses

Calabrese, Edward J.; Hanekamp, Jaap C.; Hanekamp, Yannic N.; Kapoor, Rachna; Dhawan, Gaurav; Agathokleous, Evgenios

The use of chloroquine in the treatment of COVID-19 has received considerable attention. The recent intense focus on this application of chloroquine stimulated an investigation into the effects of chloroquine at low doses on highly biologically-diverse models and whether it may induce hormetic-biphasic dose response effects. The assessment revealed that hormetic effects have been commonly induced by chloroquine, affecting numerous cell types, including tumor cell lines (e.g. human breast and colon) and non-tumor cell lines, enhancing viral replication, sperm motility, various behavioral endpoints as well as decreasing risks of convulsions, and enhancing a spectrum of neuroprotective responses within a preconditioning experimental framework. These diverse and complex findings indicate that hormetic dose responses commonly occur with chloroquine treatment with a range of biological models and endpoints. These findings have implications concerning study design features including the number and spacing of doses, and suggest a range of possible clinical concerns and opportunities depending on the endpoint considered.