Hydrogen sulfide reduces kidney injury due to urinary-derived sepsis by inhibiting NF-κB expression, decreasing TNF-α levels and increasing IL-10 levels

Xian Chen; Wujun Xu; Yi Wang; Hongmei Luo; Suqin Quan; Jing Zhou; Ning Yang; Tao Zhang; Lei Wu; Jun Liu; Xiangyang Long; Neng Zhu; Huang Xie; Zhigang Luo

doi:10.3892/etm.2014.1781

Hydrogen sulfide reduces kidney injury due to urinary-derived sepsis by inhibiting NF-κB expression, decreasing TNF-α levels and increasing IL-10 levels

Exp Ther Med. 2014 Aug;8(2):464-470. doi: 10.3892/etm.2014.1781. Epub 2014 Jun 12.

Authors

Xian Chen¹, Wujun Xu¹, Yi Wang¹, Hongmei Luo², Suqin Quan¹, Jing Zhou¹, Ning Yang¹, Tao Zhang¹, Lei Wu¹, Jun Liu¹, Xiangyang Long¹, Neng Zhu¹, Huang Xie¹, Zhigang Luo¹

Affiliations

¹ Department of Urology, Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
² Department of Histology and Embryology, University of South China, Hengyang, Hunan 421001, P.R. China.

Abstract

The present study aimed to investigate the effect of hydrogen sulfide (H₂S) on kidney injury induced by urinary-derived sepsis. Rabbits were randomly divided into control, sham, sepsis, NaHS 2.8 μmol/kg and NaHS 8.4 μmol/kg groups, with six rabbits in each group. Upper urinary tract obstruction and acute infection was induced to establish the sepsis model. Blood was collected to carry out a white blood cell (WBC) count, and creatinine (Cr) and blood urea nitrogen (BUN) analysis. Morphological changes were observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10 and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). Cystathionine-γ-lyase (CSE) activity was measured by the spectrophotometric methylene blue method and the blood H₂S concentration was measured by deproteinization. WBC, Cr and BUN levels were significantly elevated in the sepsis group compared with those in the control group (P<0.05). Following treatment with NaHS, the WBC, Cr and BUN levels were significantly decreased in the NaHS groups compared with those in the sepsis group (P<0.05). The pathological features of kidney injury were also alleviated by NaHS. In the sepsis group, the levels of TNF-α, IL-10 and NF-κB were significantly increased compared with those in the control group (P<0.05). In the NaHS groups, the TNF-α and NF-κB levels were significantly reduced whereas the IL-10 level was significantly increased compared with the respective levels in the sepsis group (P<0.05). The H₂S concentration was significantly decreased in the sepsis group and this reduction was attenuated in the NaHS groups (P<0.05). Furthermore, the NaHS 8.4 μmol/kg dose revealed a more potent effect than the NaHS 2.8 μmol/kg dose. Thus, exogenous H₂S reduced kidney injury from urinary-derived sepsis by decreasing the levels of NF-κB and TNF-α, and increasing the level of IL-10.

Keywords: IL-10; NF-κB; TNF-α; hydrogen sulfide; kidney injury; urinary-derived sepsis.