Kadry Mai O, Ali Hanaa Mahmoud
Therapeutic Chemistry Department, National Research Centre, El Buhouth St., Dokki 12622, Egypt.
Department of Genetics and Cytology, National Research Centre, Dokki 12622, Egypt.
Toxicol Rep. 2024 Nov 15;13:101816. doi: 10.1016/j.toxrep.2024.101816. eCollection 2024 Dec.
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.
肝脏和脑损伤的病理生理学包括各种分子和信号通路。评估炎症诱导的DNA损伤是研究器官畸变和突变的主要问题之一。当前研究旨在探究5-甲氧基-N-乙酰色胺（5-MNAT）和/或槲皮素（QR）对大鼠模型中由亚硝酸钠（NaNO）诱导的肝脑损伤的预防作用，以及阐明不同的交联炎症途径和神经递质。在给予（75mg/kg体重）剂量的NaNO之前，先用QR和5-MNAT进行预处理。NaNO中毒显著导致包括C反应蛋白（CRP）和白细胞介素-6（IL-6）在内的炎症生物标志物减轻。上述抗氧化剂显著改善了炎症生物标志物信号通路以及肝功能生物标志物（包括丙氨酸转氨酶（ALT）和乳酸脱氢酶（LDH））的改变。此外，它们调节了脑组织中的神经递质，包括γ-氨基丁酸（GABA）和血清素。同样，彗星试验表明这些抗氧化剂成功地减轻了NaNO诱导的肝脑DNA损伤。总之，QR和5-MNAT联合治疗在改善NaNO诱导的肝脑损伤方面显示出最有效的治疗指数，证实了这种组合作为脑缺氧有效治疗方法的有效性。尽管如此，这一点通过组织病理学研究得到了证实。
