Khelfi Abderrezak, Oussedik-Oumehdi Habiba, Laraba-Djebari Fatima
USTHB, University of Sciences and Technology Houari Boumediene, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology , BP 32, El-Alia, Bab Ezzouar, 16111, Algiers, Algeria.
Inflammation. 2022 Aug;45(4):1700-1719. doi: 10.1007/s10753-022-01654-9. Epub 2022 Mar 5.
Envenomation by Cerastes cerastes often results in local dermonecrotic lesions. While immunotherapy is effective in reversing systemic symptoms, this strategy remains deficient in counteracting the extended dermonecrosis induced from the bite site. In this study, the therapeutic effect of pharmacological drugs on the dermonecrotic activity of the venom was investigated. Venom administration caused a marked dermonecrotic lesion with increased levels of oxidative stress biomarkers (MPO, EPO, NO, HO, MDA, protein carbonyl, and thiol levels). Antioxidant capacity was decreased, as evidenced by reduced catalase, glutathione, and selenium levels. Histopathological analysis of skin biopsies revealed necrotic lesions accompanied by hemorrhage and epidermis thickening. The efficiency of cyproheptadine (C), dexamethasone (D), and tetracycline (T), as a monotherapy or in association, were evaluated on the dermonecrotic activity of the venom. Most of the treatments (CD, CT, DT, and CDT) largely reduced tissue necrosis to, respectively, 84.29, 87.83, 83.77, and 82.71% and significantly decreased MPO and EPO activities and NO, HO, MDA, and protein carbonyl levels in skin tissue homogenates. CT and CDT associations significantly increased the antioxidant status as indicated by enhanced catalase, glutathione, and selenium levels. The second challenge of the pharmacological associations was more effective in improving the oxidative/antioxidative balance. Skin tissue sections from treated animals with CT or CDT revealed tissue structure close to that observed in control animals. Therefore, the synergistic action of all tested drugs on the major pathways of inflammation (phospholipases A, metalloproteinases, and histamine) seems to be efficient to neutralize the necrotic activity of the venom.
角蝰蛇咬伤常导致局部皮肤坏死性损伤。虽然免疫疗法能有效逆转全身症状，但该策略在对抗咬伤部位引起的持续性皮肤坏死方面仍存在不足。在本研究中，研究了药物对毒液皮肤坏死活性的治疗效果。给予毒液会导致明显的皮肤坏死性损伤，氧化应激生物标志物（髓过氧化物酶、红细胞生成素、一氧化氮、血红素加氧酶、丙二醛、蛋白质羰基和巯基水平）升高。抗氧化能力下降，过氧化氢酶、谷胱甘肽和硒水平降低证明了这一点。皮肤活检的组织病理学分析显示坏死性损伤伴有出血和表皮增厚。评估了赛庚啶（C）、地塞米松（D）和四环素（T）单一疗法或联合使用对毒液皮肤坏死活性的效果。大多数治疗（CD、CT、DT和CDT）在很大程度上将组织坏死分别降至84.29%、87.83%、83.77%和82.71%，并显著降低皮肤组织匀浆中髓过氧化物酶和红细胞生成素活性以及一氧化氮、血红素加氧酶、丙二醛和蛋白质羰基水平。CT和CDT联合使用显著提高了抗氧化状态，过氧化氢酶、谷胱甘肽和硒水平升高表明了这一点。药物联合使用的第二个挑战在改善氧化/抗氧化平衡方面更有效。用CT或CDT治疗的动物的皮肤组织切片显示组织结构接近对照动物。因此，所有测试药物对炎症主要途径（磷脂酶A、金属蛋白酶和组胺）的协同作用似乎能有效中和毒液的坏死活性。
