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. 2024 May 20;10(1):FSO911.
doi: 10.2144/fsoa-2023-0117. eCollection 2024.

Fischer's oligopeptide ratio in ischemic hypoxia: prophylactic amendment of sophoretin and melatonin supplementation

Mai O Kadry  1 , Hanaa Mahmoud Ali  2
Affiliations

Fischer's oligopeptide ratio in ischemic hypoxia: prophylactic amendment of sophoretin and melatonin supplementation

Mai O Kadry et al. Future Sci OA. .

Abstract

Aim: The fundamental pathophysiology of ischemic-hypoxia is oxygen depletion. Fischer's ratio is essential for monitoring hypoxia intensity. Methods: the current study highlighted the prophylactic role of sophoretin (QRC) and/or melatonin (MLN) versus sodium nitrite (SN) brain hypoxia. Results: Prophylactic treatment with sophoretin and MLN, was preceded with hypoxia-induction via sodium nitrite (60 mg/kg, S.C.). SN decreased hemoglobin (Hb), elevated HIF-α, HSP-70, IL-6 and TNF-α. Sophoretin and/or MLN restored the ameliorated inflammatory biomarkers, modulated norepinephrine, dopamine, serotonin and gamma-aminobutyric acid (GABA). Similarly, single-cell gel electrophoresis (SCGE or COMET) DNA damage assay confirmed this finding. Conclusion: Treatment via sophoretin and MLN was the most effective therapy for improving sodium nitrite-induced brain injury.

Keywords: DNA-damage; HSP-70; IL-6; TNF-α; hypoxia; melatonin; sophoretin.

Plain language summary

Sodium nitrite is utilized as a preservative, food colorant and in medicine. However, misusage can affect human health, leading to brain injury, cyanosis, hypotension and hypoxia. Therefore, its toxic effect on the brain was investigated in addition to the potential protective impact of sophoretin and/or melatonin was also monitored. Sophoretin and melatonin revealed a positive impact on certain factors. They regulated hemoglobin level, hypoxia biomarker hypoxia inducible factor (HIF-α), inflammatory biomarkers such as TNF-α and IL-6 and heat shock protein-70 (HSP-70) and DNA damage. When these antioxidants were combined, they had a superior protective impact against brain injury and mutations.

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Influence of sophoretin and/or melatonin on brain hypoxia inducible factor gene expression and HSP-70, IL-6 and TNF-α protein expression post NaNO2-induced hypoxia. Data are expressed as means ± SEM (n = 10). A p-value <0.05 is considered significant. Groups having the same letter are not significantly different, while those having different letters are significantly different.
Figure 2.
Figure 2.
Influence of sophoretin and/or melatonin on serum dopamine, GABA, serotonin and norepinephrine levels following NaNO2-induced hypoxia. Data are expressed as means ± SEM (n = 10). A p-value <0.05 is considered significant. Groups having the same letter are not significantly different, while those having different letters are significantly different.
Figure 3.
Figure 3.
Single-cell gel electrophoresis (SCGS; COMET) assay showing the degree of DNA damage in the brain tissue. Of (A) control group revealing no significant DNA damage. (B) The SN hypoxic group revealing a highly significant DNA damage represented by tail length. (C) The sophoretin-treated group revealing low DNA damage. (D) The melatonin treated group with moderate DNA damage. (E) The sophoretin and melatonin-treated group with the lowest DNA damage.
Figure 4.
Figure 4.
Influence of sophoretin and/or melatonin on DNA damage (tail moment, length and tail DNA %) following NaNO2 induced hypoxia. (A) Percentage of tail moment, (B) percentage of untailed, (C) tailed percentage, (D) tail DNA percentage, (E) tail length in SN hypoxic group and different treated groups. Data are expressed as means ± SEM (n = 10). P-value <0.05 is considered significant. Groups having the same letter are not significantly different, while those having different letters are significantly different.
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