Effect of p-benzoquinone, a cigarette smoke-derived component, on the architecture and function of human RBC

Abstract

p-benzoquinone (pBQ), a cigarette smoke-derived component, stands as one of the lethal oxidants of cigarette smoke. Health hazards caused by cigarette smoking are a profound global health concern. It has been reported to contribute significantly to several health disorders, such as lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, etc. These adverse health effects might be attributed to the complex mixture of approximately 4,000 chemicals present in cigarette smoke, such as nicotine, tar, nitric oxide, and p-benzosemiquinone (pBSQ). pBSQ, ranging from 100-200 {micro}g per cigarette, gets oxidized to pBQ in the lungs of smokers and subsequently enters into the bloodstream. In the present study, we investigated the detrimental effect of pBQ on the architecture of human RBCs. Previously, we showed that the covalent modification of human hemoglobin with pBQ results in an alteration in its structure and function. In addition, we explored the potential neutralizing role of N-acetyl cysteine (NAC) in the reactivity of pBQ. Our results demonstrated that pBQ exposure to human red blood cells (RBCs), ex vivo, significantly decreases the reduced glutathione (GSH) content of RBCs, leading to the elevation of reactive oxygen species (ROS) and consequently causing oxidative damage to cellular components. pBQ exposure resulted in increased RBC sedimentation, altered membrane fluidity, enhanced lipid peroxidation, and significant morphological changes, such as bulging and distortion on the surface of RBCs, which eventually compromise membrane integrity. In addition, the coexistence of NAC with pBQ was found to be effective in neutralizing pBQ, thereby restoring GSH levels and RBC membrane architecture. These findings highlight the potential of NAC in mitigating the harmful effects of cigarette smoke on RBCs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/619387v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@8c3d58org.highwire.dtl.DTLVardef@10f7655org.highwire.dtl.DTLVardef@21d140org.highwire.dtl.DTLVardef@30d65c_HPS_FORMAT_FIGEXP M_FIG C_FIG