Cumene hydroperoxide debilitates macrophage physiology by inducing oxidative stress: Possible protection by α-tocopherol

Macrophages, the major phagocytes of body, are largely dependent on membrane for their apposite functioning. Cum-OOH, a catalyst used in chemical and pharmaceutical industry, is a peroxidative agent, which may induce oxidative stress in macrophages hampering the integrity of their membrane. α-Tocopherol is known to protect the membrane from oxidative modulation and preserve its integrity. In the present study, we investigated the effect of Cum-OOH on physiology of macrophages and evaluated the protective effect of α-tocopherol against Cum-OOH-induced functional impairment. An in vitro exposure to 10–200 μM Cum-OOH altered redox balance of murine peritoneal macrophages and led to a severe physiological impairment. It markedly augmented the release of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β and prostaglandin E2), lipopolysaccharide primed nitric oxide release and inducible nitric oxide synthase expression, and lysosomal hydrolases secretion. It mitigated respiratory burst and phagocytosis and intracellular killing of yeast (Saccharomyces cereviseae). Mannose receptor, a major macrophage phagocytic receptor (also implicated in S. cereviseae phagocytosis), exhibited a hampered recycling with its number being reduced to about 54% of the untreated, control cells following Cum-OOH exposure. A 24-h pretreatment of macrophages with 25 μM α-tocopherol preserved most of the assessed functions close to their corresponding control values. These data suggest that exposure to Cum-OOH may impair the physiology of immune cells such as macrophages and that supplementation with α-tocopherol can safeguard these cells against Cum-OOH toxicity.