(P01-015-23) Lycopene Reverses Hepatic Mitochondrial Function and Restores Oxidized Mt-DNA Damaged by Atrazine

Objectives: Pesticide residues in agriculture are serious environmental contaminants that can adversely affect environmental safety and organism health. Atrazine (ATZ) is a triazine herbicide with a high degree of permanence. Lycopene (LYC), widely known as an antioxidant, is a carotenoid prevalent in plants and fruits. Mitochondria, a type of eukaryotic organelle, of hepatocytes have a crucial role in metabolism, signal transduction, and energy supply. This study aimed to reveal the antioxidant function of lycopene and functional assessment of mitigation of liver injury by environmental pollutants.

Methods: The mice were divided into seven groups by randomization: blank control (Con), vehicle control (Vcon), 5mg/kg lycopene (LYC), 50mg/kg atrazine (ATZ1), 5mg/kg lycopene and 50mg/kg atrazine (ATZ1+LYC), 200mg/kg atrazine (ATZ2), 5mg/kg lycopene and 200mg/kg atrazine (ATZ2+LYC). Mitochondrial ultrastructure was observed, and mitochondrial function were examined to assess the overall mitochondrial assessment. Isolated livers were used to examine NAD^+/NADH, NADP⁺/ NADPH, ATP content, protein, and total RNA extraction. The methods of WB were used to provide a comprehensive assessment of mitochondrial dynamics, mitophagy, mitochondrial stress, mitochondrial biogenesis.

Results: The study reveals that ATZ caused vacuolization of hepatocytes and mitochondria, and reduced ATP production. Additional supplementation with LYC could maintain normal hepatocyte structure and function and restore ATP supply. ATZ caused the excessive fission of mitochondria, mitophagy, and disrupted mitochondrial biogenesis. However, LYC supplementation reversed these changes. The present study revealed a series of specific changes in hepatic mitochondrial function caused by ATZ and LYC. LYC could reverse the significantly exacerbated mitochondrial dysfunction, mitophagy, the production of oxidized mtDNA (Ox-mtDNA) and mitochondrial stress caused by ATZ.

Conclusions: This study revealed that ATZ caused oxidative damage in mitochondria, while LYC could act as an antioxidant to restore disordered mitochondrial function and oxidized mt-DNA.

Funding Sources: This study has received assistance from National Natural Science Foundation of China (No. 32172932).
*Corresponding author: Prof. Jin-Long Li. E-mail address: Jinlongli@neau.edu.cn.