Resveratrol can prevent CCl4-induced liver injury by inhibiting Notch signaling pathway

Gamze Tanriverdi; Fatma Kaya Dagistanli; Sule Ayla; Sibel Demirci; Mediha Eser; Z. Seda Unal; Mujgan Cengiz; Huseyin Oktar

Ayuda

Resveratrol can prevent CCl4-induced liver injury by inhibiting Notch signaling pathway

Gamze Tanriverdi ^[1] ; Fatma Kaya-Dagistanli ^[1] ; Sule Ayla ^[3] ; Sibel Demirci ^[1] ; Mediha Eser ^[1] ; Z. Seda Unal ^[2] ; Mujgan Cengiz ^[1] ; Huseyin Oktar ^[1]
1. [1] Istanbul University
  
  Istanbul University
  
  Turquía
2. [2] University of Kocaeli
  
  University of Kocaeli
  
  Turquía
3. [3] Medipol University Medical Faculty
Mostrar afiliaciones +
Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 31, Nº. 7, 2016, págs. 769-784
Idioma: inglés
Enlaces
- Texto completo
Resumen
- We investigated whether Notch signaling was increased in an experimental liver fibrosis model and examined the effects of resveratrol on Notch expression. Rats were divided into four groups: the control group, injected with physiological saline; the CCl4 group; the CCl4 plus resveratrol group; and the resveratrol group. After treatment, immunostaining was performed to detect Notch1, Notch3, Notch4, transforming growth factor (TGF)-beta, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA), and TUNEL assays were performed to evaluate apoptosis. Sirius red staining was used to detect fibrosis. Samples were also biochemically evaluated for glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation, and protein oxidation. GSH, GPx, and catalase activities were significantly decreased (p<0.001) in the CCl4 group. Distinct collagen accumulation was detected around the central vein and portal areas, and numbers of Notch1-, Notch3-, and Notch4-positive cells were significantly increased (p<0.001) in fibrotic areas in the CCl4 group. Increased expression of Notch proteins in fibrotic areas may support the role of Notch in mediating signaling associated with liver fibrosis through activation of hepatic stellate and progenitor cells. In contrast, resveratrol prevented liver fibrosis by decreasing lipid peroxidation and may be effective for inhibiting Notch signaling.