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

## TL;DR

This study shows that sophoretin and melatonin can protect the brain from sodium nitrite-induced hypoxia and reduce inflammation and DNA damage.

## Contribution

The novel contribution is the demonstration of sophoretin and melatonin's combined protective effects against brain injury caused by sodium nitrite-induced hypoxia.

## Key findings

- Sophoretin and melatonin reduced inflammatory biomarkers like TNF-α and IL-6 in hypoxia-induced brain injury.
- The combination of sophoretin and melatonin showed superior protection against DNA damage and neurotransmitter imbalance.
- Fischer's ratio confirmed the effectiveness of the treatment in mitigating hypoxia intensity.

## 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.

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.

Induction of hypoxia in rats via sodium nitrite in a dose of (60 mg/kg, S.C.).

Pretreatment with sophoretin and melatonin and their combination followed by sodium nitrite induced brain injury.

Monitoring the protective impact of sophoretin and melatonin on brain neurotransmitters including dopamine, norepinephrin, serotonin and GABA.

Monitoring brain inflammatory biomarkers including HIF-α, TNF-α, IL-6, HSP-70 and DNA-damage.

Performing Fischer's ratio for identifying the intensity of hypoxia.