Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer

Abstract

A multitude of extrinsic environmental factors (referred to in their entirety as the ‘skin exposome’) impact structure and function of skin and its corresponding cellular components. The complex (i.e. additive, antagonistic, or synergistic) interactions between multiple extrinsic (exposome) and intrinsic (biological) factors are important determinants of skin health outcomes. Here, we review the role of hypochlorous acid (HOCl) as an emerging component of the skin exposome serving molecular functions as an innate immune factor, environmental toxicant, and topical chemopreventive agent targeting solar UV-induced skin cancer. HOCl [and its corresponding anion (OCl-; hypochlorite)], a weak halogen-based acid and powerful oxidant, serves two seemingly unrelated molecular roles: (i) as an innate immune factor [acting as a myeloperoxidase (MPO)-derived microbicidal factor] and (ii) as a chemical disinfectant used in freshwater processing on a global scale, both in the context of drinking water safety and recreational freshwater use. Physicochemical properties (including redox potential and photon absorptivity) determine chemical reactivity of HOCl towards select biochemical targets [i.e. proteins (e.g. IKK, GRP78, HSA, Keap1/NRF2), lipids, and nucleic acids], essential to its role in innate immunity, antimicrobial disinfection, and therapeutic anti-inflammatory use. Recent studies have explored the interaction between solar UV and HOCl-related environmental co-exposures identifying a heretofore unrecognized photo-chemopreventive activity of topical HOCl and chlorination stress that blocks tumorigenic inflammatory progression in UV-induced high-risk SKH-1 mouse skin, a finding with potential implications for the prevention of human nonmelanoma skin photocarcinogenesis.

Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

“…Albumin has the ability to conjugate with aldehydes to form Schiff bases or Michael adducts by generating covalent adducts [ 78 ]. Aldehydes can react with protein and the sulfhydryl group of cysteine, thiols, and amine groups in both oxidative (lipoxidation) and non-oxidative reactions [ 78 , 79 , 80 , 81 ]. Furthermore, the addition of toxic lipid peroxidation by-product (e.g., MDA) to proteins results in an increase in carbonyl contents [ 82 ].…”

The Drinking Water and Swimming Pool Disinfectant Trichloroisocyanuric Acid Causes Chlorination Stress Enhancing Solar UV‐Induced Inflammatory Gene Expression in AP‐1 Transgenic SKH‐1 Luciferase Reporter Mouse Skin†

“…Cellular chlorination stress as a result of environmental exposure is an important molecular factor impacting public health, both with regard to recreational ( i.e . swimming pool) and drinking water use, representing a topic of essential importance to global freshwater use and safety in the 21 st century (2). In the context of ubiquitous epithelial (cutaneous, pulmonary, gastrointestinal, etc .)…”

“…Interestingly, with reference to co‐exposure scenarios involving environmental disinfectants and solar UV (such as in the context of recreational swimming pool use), only limited experimental data are available documenting cutaneous pathology and toxicological effects downstream of this environmentally relevant co‐exposure (3,5). Recently, we have published our findings employing co‐exposure models indicating that topical HOCl suppresses inflammatory photocarcinogenesis in SKH‐1 high‐risk mouse skin (2,11). In accordance with this observation, a topical HOCl regimen suppressed acute UV‐induced inflammation and AP‐1‐controlled transcriptional activity in transgenic SKH‐1 luciferase reporter mouse skin as revealed by oxidative stress RT 2 Profiler™ array analysis, substantiating the established anti‐inflammatory effect of topical HOCl harnessed clinically for therapeutic intervention targeting inflammatory pathologies including pruritus, atopic and radiation dermatitis, and psoriasis (2,14).…”

The Role of Reactive Species on Innate Immunity

“…Basic physicochemical properties of HOCl are relevant to its endogenous physiological function including its role as an innate immune factor, topical antimicrobial, and environmental toxicant [ 157 ]. HOCl is a weak halogen-based acid and a powerful chlorination agent, that contains one labile proton (pKa = 7.46) dictating the co-existence between acid and conjugated base under physiological conditions at near equimolar ratio.…”

“…HOCl is a weak halogen-based acid and a powerful chlorination agent, that contains one labile proton (pKa = 7.46) dictating the co-existence between acid and conjugated base under physiological conditions at near equimolar ratio. HOCl and its conjugated base HOCl/OCl − represent a potent oxidizing redox system [E0′ = +0.9 (OCl-); E0′ = +1.48 V (HOCl)] under physiological conditions, and serves as an endogenous microbicidal agent, generated by myeloid lineage-derived effector cells (including neutrophils) [ 157 ]. The oxidant couple HOCl/OCl − is an endogenous microbicidal agent [ 158 ].…”