Role of Oxidative Stress and Interrelated Cellular Offences in Sex Modulation of Cardiorenal Sequels of Sepsis

Sepsis is a state of multiple organ dysfunction caused by a disseminated inflammatory response to infection and ensuing metabolic and hemodynamic perturbations. Reports suggest a pivotal role for the subject sex in determining the incidence and severity of sepsis outcomes, signifying a complex interplay between sex steroids and sepsis pathophysiology. Simultaneous and correlated myocardial and renal irregularities constitute paramount hallmarks of sepsis and are often referred to as cardiorenal syndrome type 5. Although several reviews have been published on sex differences in sepsis morbidity and mortality, little or no efforts have been done to summarize integrative and molecular underpinnings of the interaction of gonadal hormonal milieus with cardiorenal injury provoked by sepsis and septic shock. In this chapter, we provide a focused and comprehensive overview of recent clinical and experimental data on the roles of sex steroids and their receptors in modulating cellular and molecular conduits incriminated in the eruption of septic cardiorenal manifestations. The offensive roles of oxidative stress and interrelated inflammatory, chemotactic, apoptotic, autophagic, coagulative, fibrinolytic, cholinergic, and adrenergic signals in this context have been discussed at length. Evidently, awareness of the significance of sexual and gonadal dimorphism in sepsis pathophysiology would facilitate the likelihood of developing personalized therapeutic modalities for managing septic cardiorenal imbalances and possibly other irregularities that are both sex and hormonal specific.