Phthalates Rapidly Increase Production of Reactive Oxygen Species in Vivo: Role of Kupffer Cells

• DOI: 10.1124/mol.59.4.744
• Publication Date: 2018-01-08T20:42:16Z
• Authors: Ivan Rusyn; Maria B. Kadiiska; Anna Dikalova; Hiroshi Kono; Ming Yin; Koichiro Tsuchiya; Ronald P. Mason; Jeffrey M. Peters; Frank J. Gonzalez; Brahm H. Segal; Steven M. Holland; Ronald G. Thurman
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Free Radicals; Kupffer Cells; Pyridines; Electron Spin Resonance Spectroscopy; NADPH Oxidases; Oxidants; Phosphoproteins; Rats; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Diethylhexyl Phthalate; Animals; Nitrogen Oxides; Peroxisome Proliferators; Spin Labels; Hexanols; Reactive Oxygen Species; Spin Trapping

The role of oxidants in the mechanism tumor promotion by peroxisome proliferators remains controversial. idea that induction acyl-coenzyme A oxidase leads to increased production H₂O₂, which damages DNA, seems unlikely; still, free radicals might be important signaling specialized cell types such as Kupffer cells, produce mitogens. Because hard evidence for oxidant vivo after treatment with is lacking, spin-trapping technique and electron spin resonance spectroscopy were used. Rats given di(2-ethylhexyl) phthalate (DEHP) acutely. trapping agent α-(4-pyridyl-1-oxide)-<i>N-tert</i>-butylnitrone was also bile samples collected 4 h. Under these conditions, intensity six-line radical adduct signal a maximum value 2.5-fold 2 h administration DEHP, before peroxisomal oxidases induced. Furthermore, DEHP [¹³C₂]dimethyl sulfoxide produced 12-line spectrum, providing stimulates ^⋅OH formation vivo. when rats pretreated dietary glycine, inactivates did not increase signals. Moreover, similar treatments performed knockout mice deficient NADPH (p47^phox subunit). Importantly, wild-type but oxidase-deficient mice. These data provide hypothesis molecular source induced cells. On contrary, affected proliferator-activated receptor α observations represent first direct, phthalates liver are