Journal Article

Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways

Fawzy, Michael A., El-Rehany, Mahmoud A., Maher, Sherif A., Albezrah, Nisreen K. A., Welson, Nermeen N., Fathy, Moustafa, Batiha, Gaber El-Saber

2022

Overview

Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI). One-hundred-and-twenty-eight healthy male Wistar albino rats were included. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were assessed. ELISA was used to estimate the pro-inflammatory cytokines. The expression of Bcl-2 and Bax genes was assessed by quantitative real-time PCR. ERK1/2, JNK1/2, p38, cleaved caspase-3, and NF-κB proteins expressions were estimated using western blot assay. The kidneys were also histopathologically studied. The IRI resulted in impaired cellular functions with increased creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, and IL-1β serum levels, and up-regulated NF-ĸB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it down-regulated the expression of the Bcl-2 gene and upregulated the Bax gene. The treatment with vincamine, in addition to pantoprazole multiple doses, significantly alleviated the biochemical and histopathological changes more than pantoprazole or vincamine alone, whether the dose is single or multiple, declaring their synergistic effect. In conclusion, vincamine with pantoprazole multiple doses mitigated the renal IRI through the inhibition of apoptosis, attenuation of the extracellular signaling pathways through proinflammatory cytokines’ levels, and suppression of the MAPK (ERK1/2, JNK, p38)–NF-κB intracellular signaling pathway.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Apoptosis / Apoptosis - drug effects / Biomarkers / Biopsy / Cytokines / Cytokines - metabolism / Disease Management / Disease Models, Animal / Disease Susceptibility / Gene expression / Immunohistochemistry / Inflammation Mediators - metabolism / Ischemia / Kidney Diseases - drug therapy / Kidney Diseases - etiology / Kidney Diseases - metabolism / Kidneys / Kinases / Male / MAP Kinase Signaling System - drug effects / MAPK / pantoprazole / Pantoprazole - pharmacology / Proteins / Rats / Reactive oxygen species / renal ischemia/reperfusion injury / Reperfusion Injury - drug therapy / Reperfusion Injury - etiology / Reperfusion Injury - metabolism / ROS / Tumor necrosis factor-TNF / vincamine / Vincamine - pharmacology