الفهرس 
Chapter 1 : ReviewOnly 14 pages are availabe for public view
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Abstract
Introduction: Pantoprazole has an antioxidant function and protects the cardiac cell by killing cell-damaging ROS. Moreover, vincamine is an indole alkaloid of clinical use against the central nervous system’s brain sclerosis and postoperative conditions. It appears to act as an oxygen vector in living cells. However, their functions and mechanisms in Ischemia-reperfusion injury remain unknown. This study aimed to investigate, for the first time, the effect of vincamine as a herbal medication in addition to pantoprazole as a synthetic drug on renal IRI in rats.
Methods: One hundred twenty-eight healthy male Wistar albino rats were used in this study. Serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA) levels were assessed. The enzyme-linked immunosorbent assay (ELISA) was used to estimate the pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. MAPK (ERK1/2, JNK, p38) and NF-κB proteins expressions were investigated by western blot assay, histopathological study for kidney was also studied.
Key findings: IRI resulted in tissue damage with impaired cell function, the elevation of serum levels of Scr, BUN, MDA, proinflammatory cytokines (TNF-α, IL-6, IL-1β), and up-regulation of NF-ĸB, JNK, ERK, and p38 proteins. Furthermore, it down-regulated the expression of Bcl-2 gene and up-regulated Bax gene. Treatment of the injured rats with vincamine as a herbal medication in addition to pantoprazole as a synthetic drug multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes more than pantoprazole alone or vincamine alone, whether the dose is once or multiple doses. This is due to the synergistic effect between them. Treatment of the injured rats with vincamine as a herbal medication in addition to pantoprazole as a synthetic drug multiple doses attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-ĸB, JNK, ERK, p38 proteins, Bax gene, and up-regulated Bcl-2 gene expression.
Conclusion
This research demonstrated, for the first time, that the potent anti-inflammatory and anti-apoptotic effects of vincamine with pantoprazole multiple doses were responsible for the attenuation of IRI that induced renal injury and apoptosis. It suppressed apoptosis via modulation of the expression of Bax and Bcl-2 genes. Furthermore, it attenuated the extracellular signaling pathways, the pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and deactivated the intracellular signaling pathways, MAPK (ERK1/2, JNK, p38), and NF-κB due to the synergistic effect between vincamine and pantoprazole.