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. 2023 May;16(5):682-688.
doi: 10.25122/jml-2022-0287.

The effect of JQ1 systemic administration on oxidative stress and apoptotic markers in renal ischemic reperfusion injury in a rat model

Saba Sahib Younis  1 , Fadhaa Abdul Ameer Ghafil  2 , Sahar Majeed  2 , Najah Rayish Hadi  1
Affiliations

The effect of JQ1 systemic administration on oxidative stress and apoptotic markers in renal ischemic reperfusion injury in a rat model

Saba Sahib Younis et al. J Med Life. 2023 May.

Abstract

This study aimed to investigate the effects of JQ1 in a renal ischemia-reperfusion (IR) rat model. Twenty-four adult male Wistar Albino rats were randomly divided into four equal groups. The sham group underwent laparotomy without ischemia-reperfusion induction. The control group experienced bilateral renal ischemia for 30 minutes, followed by a 2-hour reperfusion period. The vehicle group (IR group + DMSO) and JQ1 group (same as in control IR + 25 mg/kg JQ1). Kidney and blood samples were collected 2 hours after reperfusion. Blood samples were used to analyze serum creatinine and blood urea nitrogen levels. Renal tissue was assessed for TNF-alpha, caspase-3, FOXO4, PI3K/AKT signaling pathway, and histological analysis. The control group exhibited significantly higher serum creatinine, blood urea nitrogen, caspase-3, TNF-alpha, and FOXO4 levels in renal tissue compared to the sham group. Additionally, the PI3K/AKT signaling pathway was significantly decreased in the control group. Histopathological examination revealed severe kidney damage in the control group compared to the sham group. In rats treated with JQ1, serum creatinine, BUN, caspase-3, TNF-alpha, and FOXO4 levels in renal tissue significantly improved. The PI3K/AKT signaling pathway was substantially increased (p-value 0.01) compared to the Vehicle and Control groups. The tubular severity score was also significantly reduced in the JQ1-treated groups compared to the Control and Vehicle groups. In conclusion, JQ1 significantly ameliorated renal ischemia-reperfusion injury in rats by suppressing apoptosis and inflammatory pathways.

Keywords: FOXO4; JQ1; PI3K/AKT; TNF-alpha; caspase-3; ischemia reperfusion injury.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Mean serum creatinine levels (mg/dl) SEM across groups (n=6 rats per group). **Significant difference JQ1 vs. vehicle, JQ1vs IRI, p-value<0.01. ***Significant difference vehicle vs. sham, p-value<0.001. ****Very high significant difference sham vs. IRI, p-value<0.0001
Figure 2.
Figure 2.
Mean serum level of urea (mg/dl) ± SEM across groups (n=6 rats per group). *Significant difference JQ1 vs. vehicle, JQ1 vs. IRI, p-value<0.01. ***High significant difference sham vs. IRI, sham vs. vehicle, p-value<0.001
Figure 3.
Figure 3.
Mean renal tissue of TNFα (ng/ml) across groups (n=6 rats per group). ****Very high significant difference sham vs. IRI, sham vs. vehicle, JQ1 vs. IRI, JQ1 vs. vehicle, p-value<0.0001
Figure 4.
Figure 4.
Mean FOXO4 concentration (ng/ml) across groups (n=6 rats per group). ****Mean highly significant difference between sham vs. IRI, sham vs. vehicle, JQ1 vs. IRI, JQ1 vs. vehicle, p-value<0.0001
Figure 5.
Figure 5.
Mean caspases-3 (ng/ml) across groups (n=6 rats per group). ****Very high significant difference sham vs. IRI, sham vs. vehicle, JQ1 vs. IRI, JQ1 vs. vehicle, p-value<0.0001
Figure 6.
Figure 6.
Mean P-AKT concentration (ng/ml) across groups (n=6 rats per group). **Mean significant difference sham vs. vehicle, p-value<0.01. ***Mean high significant difference sham vs. IRI, p-value<0.001
Figure 7.
Figure 7.
Mean PI3K levels (ng/ml) across groups at the end of the experiment (n=6 rats per group). ****Mean very high significant difference sham vs. IRI, sham vs. vehicle, JQ1vs IRI, JQ1vs vehicle, p-value<0.0001
Figure 8.
Figure 8.
Renal segment from histopathological analysis. A: renal segment photomicrograph for the sham group, kidney of the rat with normal histology of mean intensity score of tubular damage in the sham group in the renal tubules H&E, 400x; B: photomicrograph shows the control group's renal portion: kidney of the rat with score 4 ischemic reperfusion damage of renal tubules. Increased cytoplasmic eosinophilia, cellular swell, loss of the brush border, and presence of eosinophilic casts, hemorrhage (black arrows) surrounded renal tubules and glomerulus, and occupied spaces of the necrotic renal tubule, H&E, 400X; C: renal segment photomicrograph for the vehicle group, kidney of the rat with score 4 ischemic reperfusion damage of renal tubules. Diffuse cellular swelling, increased cytoplasmic eosinophilia, loss of brush border, and hemorrhage/ necrosis of epithelial cells (black arrows) of renal tubules of cortex area, where the inflammatory exudate (yellow arrows) was observed in the lumen of renal tubules under necrosis, H&E 400X; D: renal segment photomicrograph for the JQ1 treatment group, kidney of the rat with score 1 ischemic reperfusion damage affect 25% of renal tubules cellular swelling, and increase cytoplasmic eosinophilia. H&E 400x.
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References

    1. Sener G, Sehirli O, Velioğlu-Oğünç A, Cetinel S, et al. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res. 2006 Jul;54(1):65–71. doi: 10.1016/j.phrs.2006.02.007.. - DOI - PubMed
    1. Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev. 2015 Jun 1;4(2):20–7. doi: 10.12861/jrip.2015.06.. - DOI - PMC - PubMed
    1. Salvadori M, Rosso G, Bertoni E. Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment. World Journal of Transplantation. 2015;5(2):52–67. doi: 10.5500/wjt.v5.i2.52. - DOI - PMC - PubMed
    1. Nakesha T, Sasaki KI, Kajimoto H, Koiwaya H, et al. FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs. PLoS One. 2014 Mar 24;9(3):e92626. - PMC - PubMed
    1. Moledina DG, Parikh CR. Phenotyping of acute kidney injury: Beyond serum creatinine. Semin Nephrol. 2018 Jan;38(1):3–11. doi: 10.1016/j.semnephrol.2017.09.002.. - DOI - PMC - PubMed

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