ROS/ER stress contributes to trimethyltin chloride-mediated hepatotoxicity; Tea polyphenols alleviate apoptosis and immunosuppression.
Comp Biochem Physiol C Toxicol Pharmacol
; 263: 109505, 2023 Jan.
Article
em En
| MEDLINE
| ID: mdl-36370998
ABSTRACT
Trimethyltin chloride (TMT) is an organotin-based contaminant present in the water environment that poses a great threat to aquatic organisms and humans. The liver is the detoxification organ of the body and TMT exposure accumulates in the liver. Tea polyphenol (TP) is a natural antioxidant extracted from tea leaves and has been widely used as a food and feed additive. To investigate the mechanism of toxicity caused by TMT exposure on grass carp hepatocytes (L8824 cells) and the mitigating effect of TP, we established a hepatocyte model of TMT toxicity and/or TP treatment. L8824 cells were treated with 0.5 µM of TMT and/or 4 µg/mL of TP for 24 h and assayed for relevant indices. The results showed that TMT exposure caused oxidative stress, resulting in increased intracellular ROS content, resulting in intracellular ROS accumulation and increased MDA content, and inhibiting the activities of T-AOC, SOD, CAT, and GSH. Meanwhile, TMT exposure activated the endoplasmic reticulum apoptotic signaling pathway, resulting in abnormal expression of GRP78, ATF-6, IRE1, PERK, Caspase-3 and Caspase-12. In addition, TMT exposure also led to up-regulation of cytokines IL-1ß, IL-6, TNF-α, and decreased expression of IL-2, IFN-γ, and antimicrobial peptides Hepcidin, ß-defensin, and LEAP2. However, the addition of TP could mitigate the above changes. In conclusion, TP can alleviate TMT exposure-mediated hepatotoxicity by inhibiting ROS/ER stress in L8824 cells. In addition, this trial enriches the cytotoxicity study of TMT and provides a new theoretical basis for the use of TP as a mitigating agent for TMT.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Doença Hepática Induzida por Substâncias e Drogas
/
Polifenóis
Limite:
Humans
Idioma:
En
Revista:
Comp Biochem Physiol C Toxicol Pharmacol
Ano de publicação:
2023
Tipo de documento:
Article