title: Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations.
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.
authors.affiliation: Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst MA 01003, United States. Electronic address: edwardc@schoolph.umass.edu.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D059165:Hormesis; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D018696:Neuroprotective Agents
keywords: Adaptive response; Biphasic; Dose-response; Hormesis; Postconditioning; Preconditioning