Effects of separate or combined exposure of nonylphenol and octylphenol on central 5-HT system and related learning and memory in the rats

Ecotoxicol Environ Saf. 2019 May 15:172:523-529. doi: 10.1016/j.ecoenv.2019.02.007. Epub 2019 Feb 8.

Abstract

This study evaluated toxic effects of nonylphenol (NP) and octylphenol (OP) on central 5-hydroxytryptamine (5-HT) system and related learning and memory in the rats. Male Sprague-Dawley rats were exposed to NP (30, 90, or 270 mg/kg), OP (40, 120, or 360 mg/kg), or a mixture of NP and OP [(mixed with the corresponding NP, OP alone exposed low, medium and high dose according to the natural environment exists NP:OP = 4:1; NOL (24 mg/kg NP+8 mg/kg OP), NOM (72 mg/kg NP+24 mg/kg OP), NOH (216 mg/kg NP+72 mg/kg OP)] by gavage every other day for 30 d. Learning and memory were assessed using a passive-avoidance test. Levels of estrogen receptor β (ERβ), 5-HT, tryptophan hydroxylase 2 (TPH2), monoamine oxidase (MAOA) enzyme, serotonin transporter (SERT), the vesicular monoamine transporter 2 (VMAT2), 5-hydroxytryptamine 1 A (5-HT1A), 5-hydroxytryptamine 3 A (5-HT3A), 5-hydroxytryptamine 3B (5-HT3B), 5-hydroxytryptamine 4 A (5-HT4A) and 5-hydroxytryptamine 6 A (5-HT6A) were measured using ELISA kits. Levels of ERβ, MAOA, SERT, VMAT2, 5-HT1A, 5-HT3A, 5-HT3B, 5-HT4A and 5-HT6A in rat hippocampal reduced by a high dose of NP and/or OP. Levels of TPH2 in rat midbrain and 5-HT in rat hippocampal increased by a high dose of NP and/or OP. In addition, latency was significantly shorter and errors were significantly greater in the high dose NP and NP+OP (NO) groups. Taken together, these results suggest that NP and/or OP may affect learning and memory in rats by inhibiting levels of ERβ, which could then lead to decreases in levels of 5-HT1A, 5-HT3A, 5-HT3B, 5-HT4A, and 5-HT6A in the rat hippocampus. These findings suggested that separate and combined exposure to NP and OP could produce toxic effects on central 5-HT system and related learning and memory in the rats.

Keywords: Central 5-HT system; Learning and memory; NP; OP.

MeSH terms

  • Animals
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Learning / drug effects*
  • Male
  • Memory / drug effects*
  • Monoamine Oxidase / metabolism
  • Phenols / toxicity*
  • RNA-Binding Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / toxicity*
  • Tryptophan Hydroxylase / metabolism
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Phenols
  • RNA-Binding Proteins
  • Sert1 protein, rat
  • Slc18a2 protein, rat
  • Vesicular Monoamine Transport Proteins
  • octylphenol
  • Serotonin
  • nonylphenol
  • Tryptophan Hydroxylase
  • tph2 protein, rat
  • Monoamine Oxidase