Fig. 1

Hydrogen peroxide and disease: A unified mechanism of pathogenesis. Environmental oxidative stress (infections, stress, xenobiotics etc.) leads to increased cellular hydrogen peroxide (H₂O₂). Significantly elevated levels of H₂O₂ have been documented in the colonic mucosa of patients with ulcerative colitis prior to the appearance of colitis, and toxic levels of H₂O₂ have been reported in blood of patients with sepsis. Cumulative evidence also supports a casual role for excess lymphocyte and macrophage H₂O₂ in the pathogenesis of systemic lupus erythematosus. H₂O₂ has distinct properties that can lead to the development of each disease. They are: 1) increased by environmental oxidative stress exposure; 2) Potent apoptotic agent; 3) Impairment of phagocytosis; 4) Biomembrane permeability; 5) Chemotactic for neutrophils; 6) Oxidant induced intestinal barrier disruption; 7) Enzyme inhibition and 8) Hypotensive agent (Pravda 2005; Shenep et al. 1985; Pravda 2019a; Redza-Dutordoir and Averill-Bates 2016; Xiang et al. 2016; Oosting et al. 1990; Möller et al. 2019; Klyubin et al. 1996; Rao et al. 1997; Tatsumi and Kako 1993; Tretter and Adam-Vizi 2000) The resulting disease phenotype is a function of one or more properties of H₂O₂ and the target cell in which H₂O₂ accumulate; i.e., lymphocytes and macrophages in SLE, colonic epithelium in ulcerative colitis and systemic accumulation in sepsis. The capacity of cellular H₂O₂ to increase in response to environmental oxidative stressors is critical to disease development. Determination of specific cell target and subsequent disease phenotype is dependent upon environmental oxidant stress exposure and differential tissue reductive (H₂O₂ neutralizing) capacity influenced by genetic or epigenetic predisposition