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Hormesis

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Hormesis

Hormesis is a two-phased dose-response relationship to an environmental agent whereby low-dose amounts have a beneficial effect and high-dose amounts are either inhibitory to function or toxic. Within the hormetic zone, the biological response to low-dose amounts of some stressors is generally favorable. An example is the breathing of oxygen, which is required in low amounts (in air) via respiration in living animals, but can be toxic in high amounts, even in a managed clinical setting.

In toxicology, hormesis is a dose-response phenomenon to xenobiotics or other stressors. In physiology and nutrition, hormesis has regions extending from low-dose deficiencies to homeostasis, and potential toxicity at high levels. Physiological concentrations of an agent above or below homeostasis may adversely affect an organism, where the hormetic zone is a region of homeostasis of balanced nutrition. In pharmacology, the hormetic zone is similar to the therapeutic window.

In the context of toxicology, the hormesis model of dose response is vigorously debated. The biochemical mechanisms by which hormesis works (particularly in applied cases pertaining to behavior and toxins) remain under early laboratory research and are not well understood.

The term "hormesis" derives from Greek hórmēsis for "rapid motion, eagerness", itself from ancient Greek hormáein to excite. The same Greek root provides the word hormone. The term "hormetics" is used for the study of hormesis. The word hormesis was first reported in English in 1943.

A form of hormesis famous in antiquity was Mithridatism, the practice whereby Mithridates VI of Pontus supposedly made himself immune to a variety of toxins by regular exposure to small doses. Mithridate and theriac, polypharmaceutical electuaries claiming descent from his formula and initially including flesh from poisonous animals, were consumed for centuries by emperors, kings, and queens as protection against poison and ill health. In the Renaissance, the Swiss doctor Paracelsus said, "All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison."

German pharmacologist Hugo Schulz first described such a phenomenon in 1888 following his own observations that the growth of yeast could be stimulated by small doses of poisons. This was coupled with the work of German physician Rudolph Arndt, who studied animals given low doses of drugs, eventually giving rise to the Arndt–Schulz rule. Arndt's advocacy of homeopathy contributed to the rule's diminished credibility in the 1920s and 1930s. The term "hormesis" was coined and used for the first time in a scientific paper by Chester M. Southam and J. Ehrlich in 1943 in the journal Phytopathology, volume 33, pp. 517–541.

In 2004, Edward Calabrese evaluated the concept of hormesis. Over 600 substances show a U-shaped dose–response relationship; Calabrese and Baldwin wrote: "One percent (195 out of 20,285) of the published articles contained 668 dose-response relationships that met the entry criteria [of a U-shaped response indicative of hormesis]"

Carbon monoxide is produced in small quantities across phylogenetic kingdoms, where it has essential roles as a neurotransmitter (subcategorized as a gasotransmitter). The majority of endogenous carbon monoxide is produced by heme oxygenase; the loss of heme oxygenase and subsequent loss of carbon monoxide signaling has catastrophic implications for an organism. In addition to physiological roles, small amounts of carbon monoxide can be inhaled or administered in the form of carbon monoxide-releasing molecules as a therapeutic agent.

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