Results
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