Senna alata with Selenium Mitigates Liver and Kidney Injury from Isoniazid and Rifampicin in Mice

Oluwadunni Joan Okwulu, Ibrahim Lawal, Naomi Oghenefega Danjuma-Audu, Mathew Olawale Abatan
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Abstract

Aim: This study aimed to evaluate the ameliorative potentials of S. alata in combination with Selenium on liver and kidney injury induced by Isoniazid-Rifampicin (INH-RIF). Study Design: Original Research work. Place and Duration of Study: Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development (NIPRD), Idu, Abuja, between August and October 2023.  Methods: Hydroethanolic extract of S. alata (EESA) was obtained by maceration, 25 Swiss mice (25-35g) were divided into 5 groups, GP1 received distill water, GP 2-5 INH-RIF 150mg/kg for the first two days; while groups 3-5 received S.alata 100mg/kg, 200mg/kg and 400mg/kg in combinAtion with Selenium 1mg/kg respectively from day 3 till day 14 orally. Sera samples were obtained and organs (liver and kidney) for weighing and histopathology on day 15. Results: This study showed that S.alata (EESA) (100mg/kg) and Selenium (1mg/kg) showed no reduction (P>.05) in the biochemical parameters (AST, ALP, ALT, BUN, Uric acid, and creatinine); histo-anatomy of both organs showed injury. The 200mg/kg EESA/Se (1mg/kg) reduced significantly (P<.05) elevated parameters for liver only (ALT, ALP); liver histo-picture showed no lesion; 400mg/kg combination decreased all parameters significantly (P<.05); histo-pathology showed no lesion in both organs. Weights of the liver showed significant reduction (P=.0025, .0052, and .0027) at 100, 200, and 400mg/kg respectively; but no significant difference in weights of the kidney compared to the toxic group. Conclusion: It was concluded that EESA 200mg/kg with Selenium 1mg/kg can mitigate the toxic effects of Isoniazid-Rifampicin on the liver, while EESA/Se 400mg/kg combination has ameliorative potentials on liver and kidney toxicity from INH-RIF. These effects may be dose-dependent. It was recommended that 400mg/kg of EESA and 1mg/kg of Selenium combination be considered in drug development.
番泻叶与硒能减轻异烟肼和利福平对小鼠肝肾的损伤
目的:本研究旨在评估金盏花与硒结合对异烟肼-利福平(INH-RIF)引起的肝肾损伤的改善潜力:原创性研究工作:研究地点和时间:阿布贾伊杜国家药物研究与发展研究所(NIPRD)药理学和毒理学系,2023 年 8 月至 10 月。方法:通过浸渍法获得金莲花水乙醇提取物(EESA),将 25 只瑞士小鼠(25-35 克)分为 5 组,GP1 组接受蒸馏水,GP2-5 组在前两天接受 INH-RIF 150 毫克/千克;而第 3-5 组从第 3 天起至第 14 天分别口服金莲花 100 毫克/千克、200 毫克/千克和 400 毫克/千克,并结合硒 1 毫克/千克。第 15 天采集血清样本,并对器官(肝脏和肾脏)进行称重和组织病理学检查:研究结果表明,白花蛇舌草(EESA)(100 毫克/千克)和硒(1 毫克/千克)对生化指标(谷草转氨酶(AST)、谷丙转氨酶(ALP)、谷草转氨酶(ALT)、尿素氮(BUN)、尿酸(Uric acid)和肌酐(Creatinine))没有降低作用(P>.05);两个器官的组织解剖显示均有损伤。200 毫克/千克 EESA/Se(1 毫克/千克)仅显著降低了肝脏升高的参数(谷丙转氨酶、谷草转氨酶)(P<.05);肝脏组织切片显示无损伤;400 毫克/千克组合显著降低了所有参数(P<.05);组织病理学显示两个器官均无损伤。肝脏重量在100、200和400毫克/千克时分别有明显下降(P=.0025、.0052和.0027),但肾脏重量与中毒组相比无明显差异:结论:EESA 200毫克/千克和硒1毫克/千克可减轻异烟肼-利福平对肝脏的毒性作用,而EESA/Se 400毫克/千克组合对INH-RIF引起的肝脏和肾脏毒性具有改善潜力。这些作用可能与剂量有关。建议在药物开发中考虑将 400 毫克/千克的 EESA 和 1 毫克/千克的硒结合使用。
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