Hormesis: Decoding Two Sides of the Same Coin

Abstract

In the paradigm of drug administration, determining the correct dosage of a therapeutic is often a challenge. Several drugs have been noted to demonstrate contradictory effects per se at high and low doses. This duality in function of a drug at different concentrations is known as hormesis. Therefore, it becomes necessary to study these biphasic functions in order to understand the mechanistic basis of their effects. In this article, we focus on different molecules and pathways associated with diseases that possess a duality in their function and thus prove to be the seat of hormesis. In particular, we have highlighted the pathways and factors involved in the progression of cancer and how the biphasic behavior of the molecules involved can alter the manifestations of cancer. Because of the pragmatic role that it exhibits, the imminent need is to draw attention to the concept of hormesis. Herein, we also discuss different stressors that trigger hormesis and how stress-mediated responses increase the overall adaptive response of an individual to stress stimulus. We talk about common pathways through which cancer progresses (such as nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 (Nrf2-Keap1), sirtuin-forkhead box O (SIRT-FOXO) and others), analyzing how diverse molecules associated with these pathways conform to hormesis.

Anti-inflammatory potential of invasive sun corals (Scleractinia: Tubastraea spp.) from Brazil: alternative use for management?

“…It is noteworthy that its 0.02 mg/kg concentration demonstrated similar results to indomethacin at 1 h, 3 h and 4 h and better than 20 mg/kg concentration. When the lower concentration of a molecule generates a more potent response than larger concentrations, the hormesis effect can be considered …”

C57BL/6 Substrains Exhibit Different Responses to Acute Carbon Tetrachloride Exposure: Implications for Work Involving Transgenic Mice

“…Hormesis can be defined as low doses of a stressor being beneficial to survival while high doses of the same stressor are detrimental. It often refers to a chemical insult, but can also refer to adaptations to stress 55,56 . If hormesis is considered in this scenario, 6J mice, which have had a non-functional NNT enzyme, have likely adapted to the lower antioxidant capacity in other ways.…”

Preclinical Studies of a Kidney Safe Iodinated Contrast Agent

“…A similar U‐shaped curve for SBECD nephroprotection from methotrexate was found previously, with its optimum mole ratio being 1:0.50, ie, much higher than found for iohexol, due to the greater nephrotoxicity of methotrexate. Hormetic mechanisms involve competing processes resulting in opposite effects in different dose ranges . Cell signaling pathways are key examples of known hormetic systems, discussed by Calebrese .…”

“…Hormetic mechanisms involve competing processes resulting in opposite effects in different dose ranges. 34,35 Cell signaling pathways are key examples of known hormetic systems, discussed by Calebrese. 34 Fig 8.…”