Oral exposure of Kunming mice to diisononyl phthalate induces hepatic and renal tissue injury through the accumulation of ROS. Protective effect of melatonin

Food Chem Toxicol. 2014 Jun:68:247-56. doi: 10.1016/j.fct.2014.03.027. Epub 2014 Mar 29.

Abstract

Diisononyl phthalate (DINP) has been widely used in polyvinyl chloride (PVC) products and is ubiquitous as a substitute; however, its toxicity due to exposure remains to be determined. This study investigated the oxidative damage induced by DINP and the induced production of the pro-inflammation cytokines interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). Oral exposure to DINP induced oxidative damage and inflammatory responses in liver and kidney tissues through the accumulation of ROS, which may be an underlying mechanism for its toxicity. These changes may contribute to hepatic and renal histopathological alterations. Our data suggest that oxidative stress is involved in DINP-induced toxicity and that the co-administration of melatonin exerts a protective effect against DINP-induced toxicity.

Keywords: Diisononyl phthalate; Interleukin-1; Melatonin; Oxidative stress; Reactive oxygen species; Tumour necrosis factor α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Interleukin-1 / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Melatonin / pharmacology*
  • Mice
  • Oxidative Stress / drug effects
  • Phthalic Acids / administration & dosage*
  • Phthalic Acids / adverse effects*
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1
  • Phthalic Acids
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • diisononyl phthalate
  • Melatonin