ReferenceID 2513
Chronic exposure to nonylphenol induces oxidative stress and liver damage in male zebrafish (Danio rerio): Mechanistic insight into cellular energy sensors, lipid accumulation and immune modulation
Chem Biol Interact
Nonylphenol (NP), an environmentally persistent and toxic endocrine-disrupting chemical with estrogenic properties, has severe implications on humans and wildlife. Accumulating evidence demonstrates the toxic response of
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 2513
- Evidence Id
- 19103
- Core Evidence Id
- 19103
- Source Reference Id
- 5024
- Herb2 Reference Id
- HBREF005821
- Subject Paper Key
- HBIN037271_34843692
- Pubmed Id
- 34843692
- Doi
- 10.1016/j.cbi.2021.109762
- Paper Title
- Chronic exposure to nonylphenol induces oxidative stress and liver damage in male zebrafish (Danio rerio): Mechanistic insight into cellular energy sensors, lipid accumulation and immune modulation
- Paper Abstract
- Nonylphenol (NP), an environmentally persistent and toxic endocrine-disrupting chemical with estrogenic properties, has severe implications on humans and wildlife. Accumulating evidence demonstrates the toxic response of NP on the developmental process, nervous system, and reproductive parameters. Although NP exposure has been implicated in chronic liver injury, the underlying events associated with hepatic pathophysiology remain less investigated. Using male zebrafish (Danio rerio) as the model, the present study investigates the impact of environmentally relevant concentrations of NP (50 and 100 mug/L, 21 days) on hepatic redox homeostasis vis-a-vis cellular energy sensors, inflammatory response, and cell death involving a mechanistic insight into estrogen receptor (ER) modulation. Our results demonstrate that congruent with significant alteration in transcript abundance of antioxidant enzymes (SOD1, SOD2, Catalase, GPx1a, GSTalpha1), chronic exposure to NP promotes ROS synthesis, more specifically superoxide anions and H2O2 levels, and lipid peroxidation potentially through elevated NOX4 expression. Importantly, NP perturbation of markers associated with fatty acid biosynthesis (srebf1/fasn) and cellular energy-sensing network (sirt1/ampkalpha/pgc1alpha) indicates dysregulated energy homeostasis, metabolic disruption, and macrovesicular steatosis, albeit with differential sensitivity at the dose level tested. Besides, elevated p38-MAPK phosphorylation (activation) together with loss of ER homeostasis at both mRNA (esr1, esr2a, esr2b) and protein (ERalpha, ERbeta) levels suggest that NP modulation of ER abundance may have a significant influence on hepatic events. Elevated expression of inflammatory markers (TLR4, p-NF-kappaB, TNF-alpha, IL-6, IL-1beta, and NOS2) and pro-apoptotic and necrotic regulators, e.g., Bax, caspase- 8, -9 and cleaved PARP1 (50 kDa), indicate chronic inflammation and hepatotoxicity in NP-exposed males. Collectively, elevated oxidative stress, metabolic dysregulation and immune modulation may lead to chronic liver injury in organisms exposed to metabolic disrupting chemicals.
- Journal
- Chem Biol Interact
- Publish Year
- 2022
- Experiment Subject
- human; zebrafish
- Experiment Type
- Animal Experiment
- Phenotype Related
- Hepatotoxicity; Chronic Inflammation; Chronic Liver Injury; Macrovesicular Steatosis
- Paper Title Cn
- Paper Title En
- Chronic exposure to nonylphenol induces oxidative stress and liver damage in male zebrafish (Danio rerio): Mechanistic insight into cellular energy sensors, lipid accumulation and immune modulation
- Bilingual Status
- semi_complete