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. 2020 Aug 28;18(3):1559325820949797.
doi: 10.1177/1559325820949797. eCollection 2020 Jul-Sep.

Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat's Kidneys Induced by Hypoxic Stress

Aliah R Alshanwani  1 , Sameerah Shaheen  2 , Laila M Faddah  3 , Ahlam M Alhusaini  3 , Hanaa M Ali  4   5 , Iman Hasan  3 , Hanan Hagar  1 , Raeesa Ahmed  6 , Fatima M B Alharbi  7 , Alaa AlHarthii  3
Affiliations

Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat's Kidneys Induced by Hypoxic Stress

Aliah R Alshanwani et al. Dose Response. .

Abstract

Hypoxia may lead to inflammatory responses by numerous signaling pathways. This investigation intended to inspect the defensive role of Quercetin (Quer) and/ or Melatonin (Mel) against reno toxicity induced by Sodium nitrite (Sod ntr). Sod ntr injection significantly decreased blood hemoglobin concentration (Hb) with a concurrent increase in serum tumor necrosis factor- α, interleukin-6, C-reactive protein, creatinine, and urea levels. Over protein-expression of vascular endothelial growth factor and heat shock, protein-70 and mRNA of HIF-1α were also observed. Pretreatment of the Sod ntr- injected rats with the aforementioned antioxidants; either alone or together significantly improved such parameters. Histopathological examination reinforced the previous results. It was concluded that the combined administration of Quer and Mel may be useful as a potential therapy against renal injury induced by Sod ntr. HIF-1α and HSP-70 are implicated in the induction of hypoxia and its treatment.

Keywords: CRP; HSP-70; VEGF; hypoxia; mRNA expression; melatonin; protein expression; quercetin.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Serum inflammatory markers (TNF-α, CRP) as well as Creatinine, and Urea in control, Sod ntr injected group as well as in Quer and/ or Mel treated groups. Data are expressed as means ± S.D (n = 6). P ≤ 0.001, P ≤ 0.05 are considered significant. a: compared with the normal group, b: compared with Sod ntr injected group, c: compared with Quer and Mel combination-group.
Figure 2.
Figure 2.
Inflammatory marker (Il-6)in control, Sod ntr injected group as well as in Quer and/ or Mel treated groups. Data are expressed as means ± S.D (n = 6). P ≤ 0.001, P ≤ 0.01, P ≤ 0.05 are considered significant. a: compared with the normal group, b: compared with Sod ntr injected group, c: compared with Quer and Mel combination-group.
Figure 3.
Figure 3.
VEGF and HSP-70 protein expression in control, Sod ntr injected group as well as in Quer and/ or Mel treated groups. Data are expressed as means ± S.D (n = 6). P ≤ 0.001, P ≤ 0.01, P ≤ 0.05 are considered significant. a: compared with the normal group, b: compared with Sod ntr injected group, c: compared with Quer and Mel combination-group.
Figure 4.
Figure 4.
Renal HIF-1α mRNA expression in control and, Sod ntr injected group as well as in Quer and/ or Mel treated groups. Data are expressed as means ± S.D (n = 6). P ≤ 0.001. a: compared with the normal group, b: compared with Sod nitrite induced Sod nitrite treated group, c: compared with Quer and Mel combination-group.
Figure 5.
Figure 5.
Light photomicrographs from a kidney of rat stained with Hematoxylin and Eosin (Scale bar: 100 µm), in which (A), represent normal renal corpuscles (star) and renal tubules. (arrow) . (B) section of a kidney from a rat exposed to Sod ntr showing marked degeneration of renal corpuscles (star) and renal tubules (arrow). Also, there are foci of inflammatory cellular infiltration (arrowhead). (C, D and E) are sections of a kidney from a rat exposed to Sod ntr and received Mel, Quer and combination of both of them respectively, showing marked improvement of the corpuscle and tubular degeneration and a marked decrease of the cellular infiltration especially in rats received the combination of Mel and Quer (E).
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