We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Vinpocetine attenuates 5-fluorouracil-induced intestinal injury: role of the Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3 and RIPK1/RIPK3/MLKL signals.
- Authors
Hassanein, Emad H. M.; Althagafy, Hanan S.; Mansour, Sherif M. A.; Omar, Zainab M. M.; Hussein Hassanein, Mohamed Mahmoud; Abd El-Ghafar, Omnia A. M.
- Abstract
Objectives: 5-Fluorouracil (5-FU) is a chemotherapy drug commonly prescribed in cancer management. Unfortunately, intestinal mucositis restricts 5-FU clinical use. Vinpocetine (VNP) is a synthetic alkaloid that is derived from vincamine. Our study was conducted to elucidate the intestinal protective effects of VNP on 5-FU intestinal injury in rats and explore the underlying mechanisms. Materials and methods: 5-FU was injected i.p. for five days, while VNP was given P.O (5 and 10 mg/kg). Results: VNP effectively mitigates oxidative stress by a significant increase in GSH and SOD and decreasing MDA content mediated by Nrf2, HO-1 upregulation, and significant Keap1 downregulation. VNP mitigated inflammatory perturbations by decreasing MPO, TNF-α, IL-1β, and IL-6 facilitated by downregulating NF-κB and TLR4 and upregulating SOCS3 levels. In addition, the RIPK1, RIPK3, MLKL, and caspase-8 expression levels were significantly decreased, evidenced improvement of intestinal necroptosis by VNP. Conclusion: Hence, VNP potently prevents intestinal injury induced by 5-FU by modulating Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3, and RIPK1/RIPK3/MLKL signals.
- Subjects
INTESTINAL injuries; FLUOROURACIL; CASPASES; OXIDATIVE stress; NUCLEAR factor E2 related factor
- Publication
Immunopharmacology & Immunotoxicology, 2024, Vol 46, Issue 6, p884
- ISSN
0892-3973
- Publication type
Academic Journal
- DOI
10.1080/08923973.2024.2415111