Journal
CHEMOSPHERE
Volume 271, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2021.129740
Keywords
di(2-ethylhexyl) phthalate; di-isononyl phthalate; Kidney; Oxidative stress; Lipidomics
Categories
Funding
- National Key R&D Program of China [2018YFC0114503]
- Joint Project of Medical Science and Technology Research Program of Henan Province (China) [LHGJ20190617]
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DEHP and DINP exposure at higher doses can cause oxidative damage in the kidney, leading to increased levels of reactive oxygen species and malondialdehyde, as well as elevated inflammatory status. While DEHP had the greatest impact on kidney lipidomics, DINP also induced significant changes in phospholipids diacylglycerides.
Di(2-ethylhexyl) phthalate (DEHP) has been well acknowledged for its endocrine disruption and associated metabolic diseases, leading to the search for safer industrial alternatives including di-isononyl phthalate (DINP). However, safety data for the latter chemical has been relatively scarce particularly regarding potential damage to the kidney at low doses. Five-week-old ICR male mice were exposed to vehicle, DEHP or DINP (0.05 and 4.8 mg/kg bw) daily via gavage for 5 weeks. We observed increased levels of reactive oxygen species and malondialdehyde, decreased levels of reduced glutathione, in the kidney at higher dose for both chemicals suggestive of oxidative damage. Elevated levels of inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 of the kidney further suggested inflammatory status as a result of phthalate exposure in both high dose groups. Targeted lipidomics demonstrated greatest changes in the kidney induced by high dose of DEHP, although DINP also induced significant changes in phospholipids diacylglycerides that are associated with lipid accumulation in glomerular podocytes and inflammatory responses. Our data suggest that oxidative stress may be involved in both DEHP- and DINP-induced renal lipidomic disruption and continue to question the suitability of DINP as proper DEHP substitute. (C) 2021 Elsevier Ltd. All rights reserved.
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