Extracellular hydrogen ion (H+)

Extracellular hydrogen ions (protons) are the primary determinants of the pH in the interstitial space, playing a vital role in maintaining physiological homeostasis and regulating biochemical reactions. In various pathological states, particularly within the tumor microenvironment, an overabundance of these ions leads to extracellular acidosis, which facilitates cancer cell invasion, suppresses immune cell activity, and promotes resistance to certain therapies (Gillies et al., 2004; NIH). The use of buffering agents such as L-histidine or histidine hydrochloride is a therapeutic approach designed to sequester these protons and normalize the extracellular pH (pHe). Histidine is particularly effective as a physiological buffer due to its imidazole side chain, which has a pKa near 6.0, allowing it to act as a proton sink in acidic environments (PubChem). By targeting the extracellular proton concentration, these buffers aim to disrupt the pro-tumorigenic effects of acidity and improve the delivery and efficacy of co-administered drugs.

Other names

ProtonHydronium ionExtracellular pHpHe

Chemical neutralization of extracellular protons via a buffering agent to maintain or increase local pH levels, thereby counteracting acidosis.