α‐Lipoic acid protects against microcystin‐LR induced hepatotoxicity through regeneration of glutathione via activation of Nrf2

Autor: Jun Bai, Shangchun Li, Zhixia Han, Lihong Gu, Qingbi Zhang
Rok vydání: 2020
Předmět:
Antioxidant
Microcystins
NF-E2-Related Factor 2
Health
Toxicology and Mutagenesis
Alpha-Lipoic Acid
medicine.medical_treatment
Glutathione reductase
010501 environmental sciences
Management
Monitoring
Policy and Law
Pharmacology
Toxicology
medicine.disease_cause
01 natural sciences
Antioxidants
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
medicine
Animals
Humans
0105 earth and related environmental sciences
chemistry.chemical_classification
Mice
Inbred BALB C
Reactive oxygen species
Thioctic Acid
Chemistry
Hep G2 Cells
General Medicine
Glutathione
Cytoprotection
Oxidative Stress
Glutathione Reductase
030220 oncology & carcinogenesis
Marine Toxins
Chemical and Drug Induced Liver Injury
Reactive Oxygen Species
Oxidation-Reduction
Oxidative stress
Zdroj: Environmental Toxicology. 35:738-746
ISSN: 1522-7278
1520-4081
DOI: 10.1002/tox.22908
Popis: Microcystins (MCs), as the most dominant bloom-forming strains in eutrophic surface water, can induce hepatotoxicity by oxidative stress. Alpha-lipoic acid (α-LA) is a super antioxidant that can induce the synthesis of antioxidants, such as glutathione (GSH), by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the potential molecular mechanism of α-LA regeneration of GSH remains unclear. The present study aimed to investigate whether α-LA could reduce the toxicity of MCs induced in human hepatoma (HepG2), Bel7420 cells, and BALB/c mice by activating Nrf2 to regenerate GSH. Results showed that exposure to 10 μM microcystin-leucine arginine (MC-LR) reduced viability of HepG2 and Bel7402 cells and promoted the formation of reactive oxygen species (ROS) compared with untreated cells. Moreover, the protection of α-LA included reducing the level of ROS, increasing superoxide dismutase activity, and decreasing malondialdehyde. Levels of reduced glutathione (rGSH) and rGSH/oxidized glutathione were significantly increased in cells cotreated with α-LA and MC-LR compared to those treated with MC-LR alone, indicating an ability of α-LA to attenuate oxidative stress and MC-LR-induced cytotoxicity by increasing the amount of rGSH. α-LA can mediate GSH regeneration through the Nrf2 pathway under the action of glutathione reductase in MC-LR cell lines. Furthermore, the data also showed that α-LA-induced cytoprotection against MC-LR is associated with Nrf2 mediate pathway in vivo. These findings demonstrated the potential of α-LA to resist MC-LR-induced oxidative damage of liver.
Databáze: OpenAIRE
Externí odkaz: