Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations

Pharmacol Res. 2016 Aug;110:242-264. doi: 10.1016/j.phrs.2015.12.021. Epub 2016 Jan 3.

Abstract

This article provides the first extensive documentation of the dose response features of pre- and postconditioning. Pre- and postconditioning studies with rigorous study designs, using multiple doses/concentrations along with refined dose/concentration spacing strategies, often display hormetic dose/concentration response relationships with considerable generality across biological model, inducing (i.e., conditioning) agent, challenging dose treatment, endpoint, and mechanism. Pre- and postconditioning hormesis dose/concentration-response relationships are reported for 154 diverse conditioning agents, affecting more than 550 dose/concentration responses, across a broad range of biological models and endpoints. The quantitative features of the pre- and postconditioning-induced protective responses are modest, typically being 30-60% greater than control values at maximum, findings that are consistent with a large body (>10,000) of hormetic dose/concentration responses not related to pre- and postconditioning. Regardless of the biological model, inducing agent, endpoint or mechanism, the quantitative features of hormetic dose/concentration responses are similar, suggesting that the magnitude of response is a measure of biological plasticity. This paper also provides the first documentation that hormetic effects account for preconditioning induced early (1-3h) and delayed (12-72h) windows of protection. These findings indicate that pre- and postconditioning are specific types of hormesis.

Keywords: Adaptive response; Biphasic; Dose-response; Hormesis; Postconditioning; Preconditioning.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / prevention & control*
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / adverse effects
  • Cytoprotection
  • Disease Models, Animal
  • Heart / drug effects*
  • Heart / physiopathology
  • Hormesis*
  • Humans
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / pathology
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / adverse effects
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Time Factors
  • Treatment Outcome

Substances

  • Cardiovascular Agents
  • Neuroprotective Agents