Investigation of the toxicity of a glyphosate-based herbicide in a human liver cell line: Assessing the involvement of Nrf2 pathway and protective effects of vitamin E and alpha-lipoic acid

ÜNLÜ ENDİRLİK B., BAKIR E., ÖKÇESİZ A., Guler A., HAMURCU Z., EKEN A., ...Daha Fazla

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, cilt.96, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 96
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.etap.2022.103999
  • Dergi Adı: ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Greenfile, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: Roundup, Glyphosate, Vitamin E, ?-lipoic acid, HepG2 cells, OXIDATIVE STRESS, IN-VITRO, CYTOTOXICITY, ROUNDUP, PROLIFERATION, PESTICIDES, TOCOPHEROL, APOPTOSIS, EXPOSURE, DAMAGE
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Glyphosate-based herbicides (GBHs) are the most widely used herbicides all over the world and has gained more attention in recent years because of health safety concerns. In this study, Roundup, one of the most popular glyphosate formulations, was used to evaluate cytotoxic, oxidative stress and apoptosis inducing effects of GBHs in a human hepatocellular cell line (HepG2). Roundup was shown to significantly increase cellular reactive oxygen species (ROS) levels, which lead to activation of the nuclear factor-erythroid-2-related factor 2 (Nrf2) antioxidant defense pathway including reduced levels of heme oxygenase 1 (HO-1). Furthermore, Roundup was found to induce apoptosis and further analysis confirmed involvement of a mitochondrial-dependent pathway verified by increased Bax/Bcl-2 ratios. Investigation of the protective effects of antioxidants vitamin E (Vit E) and alpha-lipoic acid (LA) against Roundup toxicity showed that both antioxidants significantly reduced the cytotoxicity, ROS formation, HO-1 downregulation, and apoptosis and that Vit E did so more efficiently than LA. In conclusion, our findings highlight the ROS producing and apoptosis inducing effects associated with GBHs, the activation of Nrf2 pathway as a defense mechanism and the protective effects of Vit E and LA against GBH toxicity.