Hormesis: Path and Progression to Significance
Abstract
:1. Introduction
2. Dose Response in Historical Context
3. The Hormesis Concept
4. How Medicine, Pharmacology, and Toxicology Got the Dose Response Half-Wrong
5. Hormetic Applications
5.1. Hazard Assessment
5.2. Risk Assessment for Carcinogens
5.3. Harmful Effects of Hormesis
5.4. Pharmaceutical Products
5.5. Parkinson’s Disease and Huntington’s Disease
6. Hormetic Mechanisms
Macrophage Polarization
7. Stem Cell Biology & Hormesis
8. Discussion/Conclusions
Funding
Conflicts of Interest
Abbreviations
AD | Alzheimer’s Disease |
ALS | Amyotrophic Lateral Sclerosis |
BEAR | Biological Effects of Atomic Radiation |
BEIR | Biological Effects of Ionizing Radiation |
FDA | Food and Drug Administration |
HD | Huntington’s Disease |
LNT | Linear Non-Threshold |
NAS | National Academy of Sciences |
PD | Parkinson’s Disease |
References
- Calabrese, E.J.; Mattson, M.P. Hormesis provides a generalized quantitative estimate of biological plasticity. J. Cell Commun. Signal. 2011, 5, 25–38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Calabrese, E.J. Overcompensation stimulation: A mechanism for hormetic effects. Crit. Rev. Toxicol. 2001, 31, 425–470. [Google Scholar] [CrossRef] [PubMed]
- Muller, H.J. Artificial transmutation of the gene. Science 1927, 66, 84–87. [Google Scholar] [CrossRef] [PubMed]
- Muller, H.J. Radiation and genetics. Am. Nat. 1930, 64, 220–257. [Google Scholar] [CrossRef]
- Calabrese, E.J. The road to linearity: Why linearity at low doses became the basis for carcinogen risk assessment. Arch. Toxicol. 2009, 83, 203–225. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Biphasic dose responses in biology, toxicology and medicine: Accounting for their generalizability and quantitative features. Environ. Pollut. 2013, 182, 452–460. [Google Scholar] [CrossRef] [PubMed]
- Timofeeff-Ressovsky, N.W.; Zimmer, K.G.; Delbruck, M. On the nature of gene mutation and gene structure. In Creating a Physical Biology: The Three-Man Paper and Early Molecular Biology; Sloan, P.R., Fogel, B., Eds.; The University of Chicago Press: Chicago, IL, USA, 2011; ISBN 9780226767826. [Google Scholar]
- Anonymous; (Genetic Panel, W.; Weaver, C.). National Academy of Sciences (NAS), Biological Effects of Atomic Radiation (BEAR), genetic effects of atomic radiation. Science 1956, 123, 1157–1164. [Google Scholar]
- Calabrese, E.J. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations. Pharmacol. Res. 2016, 110, 242–264. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Preconditioning is hormesis part II: How the conditioning dose mediates protection: Dose optimization within temporal and mechanistic frameworks. Pharamcol. Res. 2016, 110, 265–275. [Google Scholar] [CrossRef] [PubMed]
- Russell, W.L. The effect of radiation dose rate and fractionation on mutation in mice. In Repair from Genetic Radiation Damage and Differential Radiosensitivity in Germ Cells; Sobels, F.H., Ed.; Proceedings of an International Symposium; University of Leiden: Leiden, The Netherlands, 1963; pp. 205–217. [Google Scholar]
- Russell, W.L.; Russell, L.B.; Kelly, E.M. Radiation dose rate and mutation frequency. Science 1958, 128, 1546–1550. [Google Scholar] [CrossRef] [PubMed]
- Russell, W.L. Summary of the effect of dose rate on the induction of mutations by radiation in the mouse. In Environmental Effects of Producing Electric Power, Joint Committee on Atomic Energy, 91st Congress of the United States, Washington, DC, USA, October and November 1969; USA Government Printing Office: Washington, DC, USA, 1969; p. 1108. [Google Scholar]
- Calabrese, E.J. The threshold vs. LNT showdown: Dose rate findings exposed flaws in the LNT model part 1: The Russell-Muller debate. Environ. Res. 2017, 154, 435–451. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. The threshold vs. LNT showdown: Dose rate findings exposed flaws in the LNT model part 2: How a mistake led BEIR I to adopt LNT. Environ. Res. 2017, 154, 452–458. [Google Scholar] [CrossRef] [PubMed]
- US National Academy of Sciences (NAS)/National Research Council (NRC). The Effects on Populations of Exposure to Low Levels of Ionizing Radiation (BEIR I); The National Academies Press: Washington, DC, USA, 1972; p. 235. [Google Scholar]
- Calabrese, E.J. From Muller to mechanism: How LNT became the default model for cancer risk assessment. Environ. Res. 2018, 241, 289–302. [Google Scholar] [CrossRef] [PubMed]
- Samson, L.; Cairns, J. New pathway for DNA-repair in Escherichia coli. Nature 1977, 267, 281–283. [Google Scholar] [CrossRef] [PubMed]
- Olivieri, G.; Bodycote, J.; Wolff, S. Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 1984, 223, 594–597. [Google Scholar] [CrossRef] [PubMed]
- Russel, W.L. Mutagenesis in the mouse and its application to the estimation of the genetic hazards of radiation. In Advances in Radiation Research, Biology and Medicine; Duplan, J.F., Chapiro, A., Eds.; Gordon and Breach Science Publishers: New York, NY, USA, 1973; pp. 323–334. [Google Scholar]
- Azzam, E.I.; de Toledo, S.M.; Raaphorst, G.P.; Mitchel, R.E.J. Low-dose ionizing radiation decreases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells. Radiat. Res. 1996, 146, 369–373. [Google Scholar] [CrossRef] [PubMed]
- Thome, C.; Tharmalingam, S.; Pirkkanen, J.; Zarnke, A.; Lafamboise, T.; Boreham, D.R. The REPAIR Project: Examining the biological impacts of sub-background radiation exposure within SNOLAB, a deep underground laboratory. Radiat. Res. 2017, 199, 470–474. [Google Scholar] [CrossRef] [PubMed]
- Planel, H.; Soleilhavoup, J.P.; Tixador, R.; Richoilley, G.; Conter, A.; Croute, F.; Caratero, C.; Gaubin, Y. Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. Health Phys. 1987, 52, 571–578. [Google Scholar] [CrossRef] [PubMed]
- Luckey, T.D. Hormesis with Ionizing Radiation; CRC Press: Boca Raton, FL, USA, 1980; ISBN 0849358418. [Google Scholar]
- Luckey, T.D. Radiation Hormesis; CRC Press: Boca Raton, FL, USA, 1991; ISBN 9780849361593. [Google Scholar]
- Schulz, H. Zur lehre von der arzneiwirkung. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin 1887, 108, 423–445. [Google Scholar] [CrossRef]
- Schulz, H. Uber Hefegifte. Pfluger’s Archiv. fur die Gesemmte Physiol. 1888, 42, 517541. [Google Scholar]
- Branham, S.E. The effects of certain chemical compounds upon the course of gas production by baker’s yeast. J. Bacteriol. 1929, 18, 247–264. [Google Scholar] [PubMed]
- Calabrese, E.J.; Baldwin, L.A. Chemical hormesis: Its historical foundations as a biological hypothesis. Hum. Exp. Toxicol. 2000, 19, 2–31. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Baldwin, L.A. The marginalization of hormesis. Hum. Exp. Toxicol. 2000, 19, 32–40. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Baldwin, L.A. Radiation hormesis: Its historical foundations as a biological hypothesis. Hum. Exp. Toxicol. 2000, 19, 41–75. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Baldwin, L.A. Radiation hormesis: The demise of a legitimate hypothesis. Hum. Exp. Toxicol. 2000, 19, 76–84. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Baldwin, L.A. Tales of two similar hypotheses: The rise and fall of chemical and radiation hormesis. Hum. Exp. Toxicol. 2000, 19, 85–97. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Toxicology rewrites its history and rethinks its future: Giving equal focus to both harmful and beneficial effects. Environ. Toxicol. Chem. 2011, 30, 2658–2673. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Calabrese, E.J. Historical blunders: How toxicology got the dose-response relationship half right. Cell. Mol. Biol. 2005, 51, 643–654. [Google Scholar] [PubMed]
- Calabrese, E.J. Getting the dose-response wrong: Why hormesis became marginalized and the threshold model accepted. Arch. Toxicol. 2009, 83, 227–247. [Google Scholar] [CrossRef] [PubMed]
- Clark, A.J. Applied Pharmacology; P. Blakiston’s Sons: Philadelphia, PA, USA, 1927; Volume 21, pp. 590–634. [Google Scholar]
- Clark, A.J. The Mode of Action of Drugs on Cells; Elsevier Inc.: London, UK, 1933; Volume 22, pp. 589–590. [Google Scholar]
- Clark, A.J. General pharmacology. In Handbuch der Experimentellen Pharmakoligies; Hefftner, A.J., Ed.; Springer: Berlin, Germany, 1937; Volume 4, ISBN 978-3-662-28641-8. [Google Scholar]
- Stebbing, A.R.D. Hormesis—Stimulation of colony growth in cAMP anularia-flexuosa (hydrozoa) by copper, cadmium and other toxicants. Aquat. Toxicol. 1981, 1, 227–238. [Google Scholar] [CrossRef]
- Stebbing, A.R.D. Hormesis—The stimulation of growth by low-levels of inhibitors. Sci. Total Environ. 1982, 22, 213–234. [Google Scholar] [CrossRef]
- Szabadi, E. Model of 2 functionally antagonistic receptor populations activated by same agonist. J. Theor. Biol. 1977, 69, 101–112. [Google Scholar] [CrossRef]
- Calabrese, E.J.; Baldwin, L.A. Hormesis: The dose-response revolution. Ann. Rev. Pharmacol. Toxicol. 2003, 43, 175–197. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Hormesis: Why it is important to toxicology and toxicologists. Environ. Toxicol. Chem. 2008, 27, 1451–1474. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Hormesis is central to toxicology, pharmacology and risk assessment. Hum. Exp. Toxicol. 2010, 29, 249–261. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Blain, R.B. The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: An overview. Toxicol. Appl. Pharm. 2005, 202, 289–301. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Blain, R.B. The hormesis database: The occurrence of hormetic dose responses in the toxicological literature. Reg. Toxicol. Pharm. 2011, 61, 73–81. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences. Environ. Pollut. 2005, 138, 378–411. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Baldwin, L.A. Hormesis: U-shaped dose responses and their centrality in toxicology. TiPS 2001, 22, 285–291. [Google Scholar] [CrossRef]
- Calabrese, E.J. Hormetic mechanisms. Crit. Rev. Toxicol. 2013, 43, 580–606. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Mattson, M.P. How does hormesis impact biology, toxicology, and medicine? NPJ Aging Mech. Dis. 2017, 3. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Hanekamp, J.C.; Shamoun, D.Y. The EPA cancer risk assessment default model proposal: Moving away from the LNT. Dose-Response 2018, 2018, 1–4. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Shamoun, D.Y.; Hanedamp, J.C. Cancer risk assessment: Optimizing human health through linear dose-response models. Food Chem. Toxicol. 2015, 81, 137–140. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. An assessment of anxiolytic drug screening tests: Hormetic dose responses predominate. Crit. Rev. Toxicol. 2008, 38, 489–542. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Staudenmayer, J.W.; Stanek, E.J.; Hoffman, G.R. Hormesis outperforms threshold model in National Cancer Institute antitumor drug screening database. Tox. Sci. 2006, 94, 368–378. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Hoffmann, G.R.; Stanek, E.J.; Nascarella, M.A. Hormesis in high-throughput screening of antibacterial compounds in E. coli. Hum. Exp. Toxicol. 2010, 29, 667–677. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Modulation of the epileptic seizure threshold: Implications of biphasic dose responses. Crit. Rev. Toxicol. 2008, 38, 543–556. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J. Alzheimer’s disease drugs: An application of the hormetic dose-response model. Crit. Rev. Toxicol. 2008, 38, 419–451. [Google Scholar] [CrossRef] [PubMed]
- Puzzo, D.; Privitera, L.; Palmeri, A. Hormetic effect of amnloid-β peptide in synaptic plasticity and memory. Neurobiol. Aging 2012, 33, e15–e24. [Google Scholar] [CrossRef] [PubMed]
- Frizzo, M.E.D.; Dall’Onder, L.P.; Dalcin, K.B.; Souza, D.O. Riluzole enhances glutamate uptake in rat astrocyte cultures. Cell. Mol. Neurobiol. 2004, 24, 123–128. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, V.; Santoro, A.; Monti, D.; Crupi, R.; di Paola, R.; Latteri, S.; Cuzzocrea, S.; Zappia, M.; Giordano, J.; Calabrese, E.J.; et al. Aging and Parkinson’s Disease: Inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radiat. Biol. Med. 2018, 115, 80–91. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, V.; Santoro, A.; Salinaro, A.T.; Modafferi, S.; Scuto, M.; Albouchi, F.; Monti, D.; Giordano, J.; Zappia, M.; Franceschi, C.; et al. Hormetic approaches to the treatment of Parkinson’s disease: Perspective and possibilities. J. Neurosci. Res. 2018, 2018, 1–22. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Zhu, S.; Pei, Z.; Drozda, M.; Stavrovskaya, I.G.; del Signore, S.J.; Cormier, K.; Shimony, E.M.; Wang, H.; Ferrante, R.J.; et al. Inhibitors of cytochrome c release with therapeutic potential for Huntington’s disease. J. Neurosci. 2008, 28, 9473–9485. [Google Scholar] [CrossRef] [PubMed]
- Kuroiwaa, T.; Yamada, I.; Endo, S.; Hakamata, Y.; Ito, U. 3-nitropropionic acid preconditioning ameliorates delayed neurological deterioration and infarction after transient focal cerebral ischemia in gerbils. Neurosci. Lett. 2000, 283, 145–148. [Google Scholar] [CrossRef]
- Morsali, D.; Bechtold, D.; Lee, W.; Chauhdry, S.; Palchaudhuri, U.; Hassoon, P.; Snell, D.M.; Malpass, K.; Piers, T.; Pocock, J.; et al. Safinamide and flecainide protect axons and reduce microglial activation in models of multiple sclerosis. Brain 2013, 136, 1067–1082. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Escribano, B.M.; Luque, E.; Aguilar-Luque, M.; Feijoo, M.; Caballero-Villarraso, J.; Torres, L.A.; Ramirez, V.; Garcia-Maceira, F.I.; Aguera, E.; Santamaria, A.; et al. Dose-dependent S-allyl cysteine ameliorates multiple sclerosis disease-related pathology by reducing oxidative stress biomarkers of dysbiosis in experimental autoimmune encephalomyelitis. Eur. J. Pharmacol. 2017, 815, 266–273. [Google Scholar] [CrossRef] [PubMed]
- Leung, W.C.; Zheng, H.; Law, S.L.; Xue, H. Anxiolytic-like action of orally administered dl-tetrahydropalmatine in elevated plus maze. Prog. Neuron-Psychopharm. Biol. Psychiatry 2003, 27, 775–779. [Google Scholar] [CrossRef]
- Honar, H.; Riazi, K.; Homayoun, H.; Sadeghipour, H.; Rashidi, N.; Ebrahimkhani, M.R.; Mirazi, N.; Dehpour, A.R. Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures. Neuroscience 2004, 129, 733–742. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Li, C.; Chen, S.; Li, Z.; Jia, X.; Wang, K.; Bao, J.; Liang, Y.; Wang, X.; Chen, M.; et al. Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways. Redox Biol. 2017, 11, 1–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Calabrese, E.J. Flaws in the LNT single-hit model for cancer risk: An historical assessment. Environ. Res. 2017, 158, 773–788. [Google Scholar] [CrossRef] [PubMed]
- Calabrese, E.J.; Giordano, J.J.; Kozumbo, W.J.; Leak, R.K.; Bhatia, T.N. Hormesis mediates dose-sensitive shifts in macrophage activation patterns. Pharm. Res. 2018. under review. [Google Scholar]
- Genard, G.; Lucas, S.; Michiels, C. Reprogramming of tumor-associated macrophages with anticancer therapies: Radiotherapy versus chemo- and immunotherapies. Front. Immunol. 2017, 8, 828. [Google Scholar] [CrossRef] [PubMed]
- Wu, Q.; Allouch, A.; Martins, I.; Modjtahedi, N.; Deutsch, E.; Perfettini, J.-L. Macrophage biology plays a central role during ionizing radiation-elicited tumor response. Biomed. J. 2017, 40, 200–211. [Google Scholar] [CrossRef] [PubMed]
- Yuan, L.; Guan, Y.; Ma, D.; Du, H. Optimal concentration and time window for proliferation and differentiation of neural stem cells from embryonic cerebral cortex: 5% oxygen preconditioning for 72 hours. Neural Regen. Res. 2015, 10, 1516–1522. [Google Scholar] [CrossRef] [PubMed]
- Peterson, K.M.; Aly, A.; Lerman, A.; Lerman, L.O.; Rodriguez-Porcel, M. Improved survival of mesenchymal stromal cell after hypoxia preconditioning: Role of oxidative stress. Life Sci. 2011, 88, 65–73. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Muscari, C.; Giordano, E.; Bonafe, F.; Govoni, M.; Pasini, A.; Guarnieri, C. Priming adult stem cells by hypoxic pretreatments for applications in regenerative medicine. J. Biomed. Sci. 2013, 20, 63–74. [Google Scholar] [CrossRef] [PubMed]
- Kim, W.-K.; Sung, J.-H. Hypoxic culturing enhances the wound-healing potential of adipose-derived stem cells. Adv. Wound Care 2012, 1, 172–176. [Google Scholar] [CrossRef] [PubMed]
- Francis, K.R.; Wei, L. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis. 2010, 1, e22. [Google Scholar] [CrossRef] [PubMed]
- Coulter, H.L. Homeopathy and the Medical Profession; Croom Helm: New York, NY, USA, 1972; ISBN 0709918364. [Google Scholar]
- Coulter, H.L. BT Divided Legacy: The Conflict between Homeopathy and the American Medical Association, 2nd ed.; North Atlantic Book: Richmond, CA, USA, 1982; Volume 3, ISBN 0938190571. [Google Scholar]
© 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Calabrese, E.J. Hormesis: Path and Progression to Significance. Int. J. Mol. Sci. 2018, 19, 2871. https://doi.org/10.3390/ijms19102871
Calabrese EJ. Hormesis: Path and Progression to Significance. International Journal of Molecular Sciences. 2018; 19(10):2871. https://doi.org/10.3390/ijms19102871
Chicago/Turabian StyleCalabrese, Edward J. 2018. "Hormesis: Path and Progression to Significance" International Journal of Molecular Sciences 19, no. 10: 2871. https://doi.org/10.3390/ijms19102871