Endometriosis progression in tumor necrosis factor receptor p55-deficient mice: Impact on oxidative/nitrosative stress and metallomic profile

M B Delsouc, María Belén Delsouc, F Ghersa, Federica Ghersa, Ghersa F, Darío C. Ramírez, D Ramírez, M C Della Vedova, María Cecilia Della Vedova, R A Gil, Raúl A. Gil, Sandra Vallcaneras, S S Vallcaneras, Marilina Casais, Casais M, M Casais
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2018 · vol. 52 , pp. 157–165 · doi:10.1016/j.jtemb.2018.12.013 · PMID:30732877 · W2907099758
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TNFRp55-deficient mice showed larger endometriosis lesions, increased peritoneal fluid copper and strontium, and altered oxidative stress markers compared to wild-type mice.

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Abstract

The present study was conducted to investigate whether the deficiency of tumor necrosis factor receptor p55 (TNFRp55) modulates oxidative/nitrosative stress and metallomic profile into the peritoneal cavity during the experimental endometriosis progression in mice. Female C57BL/6 mice, wild-type (WT) and TNFRp55 knockout (KO) of two months were used. Endometriosis was induced experimentally by autotransplanting three pieces of the right uterine horn to the intestinal mesentery. After four weeks, endometriotic-like lesions and peritoneal lavage fluid were collected. The obtained peritoneal fluid was analyzed for nitrite levels using the Griess method and trace elements concentrations by ICP-MS. Both endometriotic-like lesions and cells isolated from peritoneal lavage were analyzed for the following oxidative/nitrosative stress markers: inducible nitric oxide synthase (iNOS) expression by Western Blot; total antioxidant capacity (TAC), the activity of two antioxidant enzymes (CAT and GPX) and thiobarbituric acid-reactive substances (TBARS) concentration, by spectrophotometric method; and protein carbonyl content and nitrotyrosine presence by ELISA. In comparison to WT group, KO mice exhibited larger lesion volume; higher levels of nitrite, copper (Cu) and strontium (Sr) in the peritoneal fluid; increased TAC, CAT, and GPX in peritoneal lavage cells; decreased concentration of TBARS in lesions and protein carbonyl in peritoneal lavage cells. Significant positive correlations between Cu and lesion volume, Sr and lesion volume, and Cu and Sr were obtained. Our results suggest that the TNFRp55 deficiency increases antioxidant protection and promotes high Cu-Sr concentrations in the peritoneal cavity, which favors the progression of experimental endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Copper Endometriosis Nitrites Receptors, Tumor Necrosis Factor, Type I Strontium Tumor Necrosis Factor Decoy Receptors Animals Antioxidants Antioxidants Copper Copper Disease Progression Endometriosis Endometriosis Female Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide Synthase Type II Nitric Oxide Synthase Type II

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