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Bisphenol-A (BPA) is a common environmental pollutant, and exposure to it is associated with proteinuria and may predict the progression of chronic kidney disease; however, the mechanism is not clear. Neutrophil extracellular traps (NETs) are a DNA skeleton coated with various proteases, and it is associated with various types of autoimmune nephritis. In this study, we examine whether NETs is involved in BPA-induced chronic kidney injury. In vivo, BPA exposure resulted in impaired renal function and altered renal morphology, including glomerular mesangial matrix expansion and increased renal interstitial fibroblast markers. Meanwhile, more dsDNA can be detected in the serum, and the NETs-associated proteins, MPO and citH3 were deposited in the renal system. In vitro, BPA and NETs treatment caused podocyte injury, a loss of marker proteins and disorder in the actin skeleton. After NETs inhibition via DNase administration, BPA-induced injuries were significantly relieved. In conclusion, the increase of NETosis in circulation and the renal system during BPA exposure suggests that NETs may be involved in BPA-induced chronic kidney injury.

Bisphenol A (BPA), one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition. However, the mechanism has not been fully elucidated. The polarization of Kupffer cells (KCs) plays an important role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs), which contributes to dysregulated lipid metabolism. The purpose of this study is to investigate the role of KC polarization in BPA-induced hepatosteatosis in male mice. In this study, we examined hepatic lipid contents and quantified M1KC in BPA-treated CD1 mice, and further explored the interaction between KCs and hepatocytes using conditional HepG2 cell culture. BPA treatment significantly increased hepatic fat contents in CD1 mice, accompanied by increased number of pro-inflammatory M1KCs and enhanced secretion of inflammatory cytokines. Increased lipid contents were also observed in HepG2 cells treated with BPA. Interestingly, higher TG contents were observed in HepaG2 cells treated with conditional media from BPA-treated KCs, compared with those treated with BPA directly. Incubation of KCs with BPA promoted the polarization of KCs to pro-inflammatory M1 dominant subtypes, which was blocked by estrogen antagonist ICI182780. Taken together, our results revealed that M1KCs polarization is involved in BPA-induced hepatic fat deposition, which is possibly associated with the estrogen receptor signaling pathway.

The effects of growth hormone (GH) and testosterone, alone or in combination, on the regulation of lipolysis in isolated adipocytes from hypophysectomized rats were investigated. Male Sprague-Dawley rats were hypophysectomized at 50 days of age. One week after operation, hormonal replacement therapy with l-thyroxine and hydrocortisone acetate was given to hypophysectomized rats. Groups of rats were treated with GH (1·33 mg/kg, daily), testosterone (10 mg/kg, once) alone or in combination. After one week of hormonal treatment, adipocytes were isolated from the pooled epididymal and perirenal fat pads and glycerol release after isoproterenol stimulation and 125I-cyanopindolol binding was measured. Hypophysectomy caused a marked decrease in basal and isoproterenol-stimulated lipolysis. There was no effect of testosterone treatment alone on lipolysis, but GH treatment resulted in an increase in isoproterenol-induced lipolysis but not to the levels observed in cells from control rats. Testosterone and GH in combination restored the lipolytic response to isoproterenol. Also 125I-cyanopindolol binding was decreased after hypophysectomy. Testosterone treatment alone and GH treatment alone increased the binding, while in combination the treatment had an additive effect. Affinity was not changed, but the effects seemed to be on receptor number, as determined by Scatchard analysis. Forskolin-stimulated cAMP accumulation in adipocytes was markedly reduced after hypophysectomy. Testosterone treatment alone had no effect. GH treatment alone increased forskolin-stimulated cAMP accumulation, although the level was lower than that found in control rats. The combined treatment resulted in a further increase to levels observed in adipocytes from control rats. These results demonstrate that GH and testosterone have additive effects in the regulation of lipolysis. Both hormones increase the β-adrenergic receptor density, partly explaining this additive effect. Moreover, GH may contribute to the lipolytic response by affecting steps distal to the receptor in the lipolytic cascade. Journal of Endocrinology (1995) 147, 147–152