Inflammatory mediators-induced DNA damage in liver and brain injury: Therapeutic approach of 5-Methoy-N-acetyltryptamine.

The pathophysiology of hepatic and cerebral damage includes various molecular and signalling pathways. Assessment of inflammation-induced DNA damage is one of the principal issues for investigating organ distortion and mutation. The current study was premeditated to discover the prophylactic role of 5-Methoy-N-acetyltryptamine (5-MNAT) and/or Quercetin (QR) versus sodium nitrite (NaNO) induced liver and brain injury in a rat model, as well as to clarify the different cross-linked inflammatory pathways and neurotransmitters. Pre-treatment with QR and 5-MNAT was followed with NaNO administration in a dose of (75 mg/kg BW). NaNO-intoxication significantly caused alleviation in inflammatory biomarkers including C-reactive protein (CRP) and interleukin-6 (IL-6). The above-mentioned antioxidants noticeably amended the altered inflammatory biomarkers signalling pathways and liver function biomarkers including alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Furthermore, they modulated brain neurotransmitters including, GABA and serotonin in brain tissue. Likewise, the COMET assay revealed that these antioxidants successfully modified NaNO-induced liver and brain DNA damage. In conclusion, treatment with both QR and 5-MNAT revealed the most effective therapeutic index in improving NaNO-induced liver and brain injury, confirming the effectiveness of this combination as a powerful treatment for brain hypoxia. Nevertheless, this was confirmed with histopathological investigation.