4.7 Article

Constant light exposure and/or pinealectomy increases susceptibility to trichloroethylene-induced hepatotoxicity and liver cancer in male mice

Journal

ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
Volume 29, Issue 40, Pages 60371-60384

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s11356-022-19976-4

Keywords

Trichloroethylene; Pollution; Melatonin; Liver cancer; Constant light; Circadian rhythm; Oxidative stress

Funding

  1. Science, Technology & Innovation Funding Authority (STDF)
  2. Competitive Funding Projects, research unit of Mansoura University
  3. Egyptian Knowledge Bank (EKB)

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Exposure to light at night, pineal gland impairment, and TCE pollution have a significant impact on health, including increased susceptibility to liver toxicity and cancer. Low melatonin levels, constant light exposure, and the combination of these factors increase the toxic and carcinogenic effects of TCE on the liver.
Exposure to light at night, pineal gland impairment, and the environmental pollutant trichloroethylene (TCE) have serious implications for health and contribute to illness, including liver cancer. The adverse effect of the association of continuous exposure to light with decreased melatonin levels and TCE-induced toxicity is not disclosed in target organs. This work explored the role of light and pineal impairment in increasing susceptibility to liver toxicity and cancer upon exposure to TCE. Male albino mice were divided into groups as follows: control group (12-h light/12-h dark cycle), constant light (24-h light), pinealectomized (Pnx) mice, sham surgically treated group, TCE-treated groups subjected to two doses (500 and 1000 mg/kg) at two different light regimens, and combination of Pnx and TCE-treated mice kept at a 12-h light/12-h dark cycle. Melatonin levels were significantly decreased in both Pnx mice and TCE-treated animals at both light regimens. Aspartate transaminase, alanine aminotransferase, activities, and serum bilirubin levels were significantly elevated, whereas albumin levels were markedly decreased in Pnx mice, TCE-treated mice, and the combination group. Histopathological investigations reflected changes in liver function parameters indicating liver injury and induction of cancer. These effects were accompanied by significant increase of the liver cancer biomarker alpha-fetoprotein and the expression of the metastatic markers CD44, TGF beta-1, and VEGF, along with increased oxidative stress indicators and inflammatory cytokines (IL-6, IL-1 beta, and TNF-alpha) in both Pnx and TCE-treated mice and the combination group at both light regimens. Taken together, our findings indicated that low melatonin levels, exposure to constant light, and the combination of both factors increases susceptibility to the toxic and carcinogenic effects of TCE on the liver.

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