Effect of gender differences on the regulation of renal ischemia-reperfusion-induced inflammation in mice

Abstract

Inflammation is a key mediator of renal ischemia-reperfusion (IR) injury. Gender disparities have been reported in acute and chronic kidney disease. In particular, males are considered to be more susceptible to renal ischemic injury compared with females according to animal studies. The purpose of the present study was to investigate the effect of gender on the renal inflammatory response following acute renal IR injury in mice. Experiments were performed in male and female C57BL/6 mice. Two weeks prior to the study, castration or ovariectomy were performed and testosterone propionate (100 μg/kg) or 17β-estradiol (100 μg/kg) was injected. Acute kidney injury (AKI) was induced by bilateral clamping of the renal pedicle for 23 min. Histological examination, western blot analysis and quantitative polymerase chain reaction were performed. In the acute renal IR injury model, the female mice were more resistant to kidney injury compared with the male mice. However, castration of the male mice reduced the levels of IR-induced tubular injury and macrophage infiltration compared with those in the injured male mice. Supplementation of testosterone reversed this protective effect in the male AKI model. Depletion of estrogen in the female mice increased the levels of IR-induced tubular injury and macrophage infiltration compared with those in the injured female mice. However, supplementation of estrogen in the ovariectomized female mice attenuated the IR-induced tubular injury and reduced the levels of macrophage infiltration. The expression levels of inflammatory cytokines, including tumor necrosis factor-α, monocyte chemotactic protein-1, interferon-γ and chemokine (C-C motif) ligand 17, were elevated in the male AKI mice compared with those in the control male mice, and were attenuated by castration. Estrogen depletion in the female mice significantly increased the expression levels of the renal inflammatory cytokines compared with those in the injured female mice, and were attenuated by estrogen supplementation in the ovariectomized female mice. These results suggested that the male gender confers greater susceptibility to IR renal injury due to an enhanced inflammatory response.

The role of L-arginine and aerobic exercise in experimental renal ischemia reperfusion injury in male and female rats

“…Finally, according to previous research, male are more sensitive to renal I/R injury than female (35), however, no difference in gender was observed in our model when L-arg or EX were administrated against kidney I/R injury.…”

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

“…However, more research is needed in this area with the use of safer and more selective agonists than nicotine. In addition, studies need to be performed across species, age, and sex to ensure consistent results and to account for the sex differences noted in both preclinical (Kang et al, 2014) as well as clinical studies demonstrating that sex plays a role in the prediction of renal decline (Halbesma et al, 2008). From preclinical studies, the sex difference Therapeutic Potential of a7 nAChRs resulted in greater renovascular vasodilation in female rat kidney tissue with the suggestion that it could be facilitated by estrogen having a direct effect on a7 nAChR downstream signaling (El-Mas et al, 2011).…”

Epigenome-Wide Association (DNA Methylation) Study of Sex Differences in Normal Human Kidney

“…Sexual disparities in response to acute and chronic renal disease have been identified for many years. Animal studies have demonstrated that males are more susceptible to renal injury compared to females [66], and females have a significantly higher ratio of survival when exposed to profound renal ischemia [67]. In the United States (as of 2014), chronic kidney disease is known to affect approximately 30 million adults, where males exhibit a higher prevalence and progression of renal disease, and is associated with a higher incidence of End Stage Renal Disease (ESRD) [68].…”