Association of resveratrol with the suppression of TNF-α/NF-kB/iNOS/HIF-1α axis-mediated fibrosis and systemic hypertension in thioacetamide-induced liver injury.
Naunyn Schmiedebergs Arch Pharmacol
; 395(9): 1087-1095, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35729229
ABSTRACT
Chronic liver injury can lead to hepatic failure and the only available method of treatment would be liver transplantation. The link between inflammation (TNF-α), nuclear factor-kappa B (NF-kB), nitrosative stress (iNOS) and hypoxia-inducible factor-1α (HIF-1α) in thioacetamide (TAA) induced liver fibrosis, and hypertension with and without the incorporation of the anti-inflammatory and antioxidant resveratrol (RES) has not been investigated before. Consequently, we injected rats with either 200 mg/kg TAA for 8 weeks starting at week 2 (model group) or pretreated them before TAA injections with RES (20 mg/kg) for 2 weeks and continued them on RES and TAA until being culled at week 10 (protective group). In the model group, we documented the induction of hepatic fibrosis and upregulation of tumor necrosis factor-α (TNF-α), NF-kB, inducible nitric oxide synthase (iNOS), HIF-1α and the profibrotic biomarkers alpha-smooth muscle actin (α-SMA) and matrix metalloproteinase-9 (MMP-9) that was significantly (p ≤ 0.0014) ameliorated by RES. RES also significantly (p ≤ 0.0232) reduced triglycerides (TG), cholesterol (CHOL), very low-density lipoprotein (vLDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure, and heart rate (HR) induction by TAA. Also, a significant (p < 0.0001) positive correlation between TNF-α/NF-kB/iNOS/HIF-1α axis-mediated fibrosis and hypertension and liver injury biomarkers was observed. These findings suggest that in the hepatotoxic compound, TAA is associated with TNF-α/NF-kB/iNOS/HIF-1α-mediated fibrosis and hypertension, whilst being inhibited by RES.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas
/
Hipertensión
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Arabia Saudita