Low-dose testosterone protects against renal ischemia-reperfusion injury by increasing renal IL-10-to-TNF-α ratio and attenuating T-cell infiltration

Abstract

Renal ischemia-reperfusion (I/R) in male rats causes reductions in plasma testosterone, and infusion of testosterone 3 h postreperfusion is protective. We tested the hypotheses that acute high doses of testosterone promote renal injury after I/R, and that acute low-dose testosterone is protective by the following: 1) increasing renal IL-10 and reducing TNF-α; 2) its effects on nitric oxide; and 3) reducing intrarenal T-cell infiltration. Rats were subjected to renal I/R, followed by intravenous infusion of vehicle or testosterone (20, 50, or 100 μg/kg) 3 h postreperfusion. Low-dose testosterone (20 μg/kg) reduced plasma creatinine, increased nitrate/nitrite excretion, increased intrarenal IL-10, and reduced intrarenal TNF-α, whereas 50 μg/kg testosterone failed to reduce plasma creatinine, increased IL-10, but failed to reduce TNF-α. A higher dose of testosterone (100 mg/kg) not only failed to reduce plasma creatinine, but significantly increased both IL-10 and TNF-α compared with other groups. Low-dose nitro-l-arginine methyl ester (1 mg·kg(-1)·day(-1)), given 2 days before I/R, prevented low-dose testosterone (20 μg/kg) from protecting against I/R injury, and was associated with lack of increase in intrarenal IL-10. Intrarenal CD4(+) and CD8(+) T cells were significantly increased with I/R, but were attenuated with low-dose testosterone, as were effector T helper 17 cells. The present studies suggest that acute, low-dose testosterone is protective against I/R AKI in males due to its effects on inflammation by reducing renal T-cell infiltration and by shifting the balance to favor anti-inflammatory cytokine production rather than proinflammatory cytokines.

Changes in the IGF-1 and TNF-α synthesis pathways before and after three-month reduction diet with low glicemic index in women with PCOS

“…Observed correlations for TNF-α in women with PCOS before dietary intervention clearly relate to anthropometric parameters linked to higher testosterone activity [28]. The effect of androgens on the increase of TNF-α was also observed by Gonzalez et al [14].…”

Androgen receptor signaling in the lungs mitigates inflammation and improves the outcome of influenza in mice

“…The only chemokine that was significantly altered by testosterone treatment was CXCL1, which was found in greater concentrations in the lungs of testosterone-treated than testosterone-depleted male mice at 3 and 14, but not 9, dpi (Fig 2E; p < 0.05). Despite the known anti-inflammatory effects of testosterone [28][29][30], testosterone treatment did not alter pulmonary concentrations of either IL-10 or TGFβ during IAV infection (Fig 2F and S1 Table). Taken together, these data suggest that the improved outcome of IAV associated with testosterone is independent of substantial changes in the 'cytokine storm' during IAV infection, at least at the time-points selected.…”

Consequences of advanced aging on renal function in chronic hyperandrogenemic female rat model: implications for aging women with polycystic ovary syndrome

“…; Patil et al. ). Kidney injury molecule‐1 (KIM‐1), proximal tubular injury biomarker, was measured in urine using an ELISA assay kit (R&D Systems, Cat# RKM 100), according to the manufacturer's instructions, as we previously described (Patil et al.…”

“…Kidney injury molecule‐1 (KIM‐1), proximal tubular injury biomarker, was measured in urine using an ELISA assay kit (R&D Systems, Cat# RKM 100), according to the manufacturer's instructions, as we previously described (Patil et al. ). KIM‐1 levels in urine were factored for the volume of urine collected over the first 24 h after reperfusion.…”