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Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.

Selenium is an important trace element with anti-cancer properties. In the present study, the apoptosis-inducing effects of organic selenium derivatives, namely methyl-L-selenocysteine and selenomethionine, were evaluated in vitro on human tumour-derived cell lines from breast, liver, colon, brain, skin and a non-tumorigenic line of epithelial origin. Apoptosis was assessed by cell-death detection immunoassay on cytoplasmic cell lysates. Breast carcinoma cells were highly sensitive to the organic selenium compounds, manifesting apoptosis at concentrations as low as 0.113 microm (0.0205 microg/ml) selenium. By contrast, non-tumorigenic mammary epithelial cells displayed poor sensitivity to selenium, requiring a substantially high concentration of the trace element of 87.9 microm (16.0 microg/ml). The cell lines derived from hepatoma and neuroblastoma showed intermediate sensitivity, with colon carcinoma cells manifesting the lowest sensitivity to the trace element. These results indicate intrinsic differences in the sensitivity of human tumour derivatives to selenium-mediated apoptosis, providing experimental support for the development of organic selenium compounds as anti-neoplastic agents against solid tumours displaying selective apoptotic sensitivity to these compounds.