Pantoprazole Attenuates MAPK (ERK1/2, JNK, p38)–NF-κB and Apoptosis Signaling Pathways after Renal Ischemia/Reperfusion Injury in Rats

Abstract

Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed. ELISA was used to estimate proinflammatory cytokines. qRT-PCR and western blot were used to investigate the gene and protein expression. Renal histopathological examination was also performed. IRI resulted in tissue damage, elevation of serum levels of creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, IL-1β, up-regulation of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it up-regulated the expression of the Bax gene and down-regulated the expression of the Bcl-2 gene. Treatment of the injured rats with pantoprazole, either single dose or multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes, attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins, and the Bax gene, and up-regulated Bcl-2 gene expression. Moreover, treatment with pantoprazole multiple doses has an ameliorative effect that is greater than pantoprazole single-dose. In conclusion, pantoprazole diminished renal IRI via suppression of apoptosis, attenuation of the pro-inflammatory cytokines’ levels, and inhibition of the intracellular signaling pathway MAPK (ERK1/2, JNK, p38)–NF-κB.

Renal Ischemia/Reperfusion Mitigation via Geraniol: The Role of Nrf-2/HO-1/NQO-1 and TLR2,4/MYD88/NFκB Pathway

“…Additionally, histological examination showed that the renal I/R group displayed severe histological alterations, indicating renal injury due to renal ischemia-reperfusion (I/R). Previous studies showed that renal I/R increased renal function markers [ 2 , 5 , 16 ] and several histological alterations [ 16 ].…”

“…Furthermore, Nrf2, HO-1, and NQO-1 gene and protein expression were slightly escalated in animals that experienced renal I/R. Numerous studies indicated that renal ischemia/reperfusion induces nuclear translocation of Nrf2 [ 7 , 16 ], with subsequent augmented levels of HO-1, SOD, and NQO-1 [ 2 , 5 , 16 ].…”

“…I/R injury often initiates non-specific inflammatory responses that can result in the loss of kidney graft viability during renal transplantation [ 1 ]. I/R-induced renal injury with accompanied renal dysfunction may cause renal failure and renal-cell death [ 2 ]. During the ischemic phase of renal I/R, the inadequate oxygen supply causes mitochondrial dysfunction [ 3 ].…”

A New EGFR Inhibitor from Ficus benghalensis Exerted Potential Anti-Inflammatory Activity via Akt/PI3K Pathway Inhibition

“…Inflammation is a crucial, specific, and self-controlled defensive mechanism that is triggered by the host in response to microbial infection, tissue injury, or trauma. However, when the triggering factors are not contained, inflammation can be associated with a dysregulation of the normal physiological processes, and the escalated response can cause serious chronic inflammatory disorders [ 1 , 2 , 3 , 4 ]. Inflammation can contribute to the pathogenesis of arthritis, stroke, cancer, neurodegenerative, and cardiovascular diseases [ 5 , 6 , 7 , 8 , 9 ].…”

Carpachromene Ameliorates Insulin Resistance in HepG2 Cells via Modulating IR/IRS1/PI3k/Akt/GSK3/FoxO1 Pathway

“…Looking for new pharmacological activities for existing candidates became essential [15][16][17][18][19][20][21][22]. Herein, we investigated, for the first time, the potential activity of carpachromene, which was shown to inhibit α-glucosidase enzyme activity [23], on glucose consumption, metabolism, and insulin signaling in a HepG2 cells insulin resistant model.…”