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The molecular mechanism underlining the preventive effect of vitamin D against hepatic and renal acute toxicity through the NrF2/ BACH1/ HO-1 pathway.
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-20 , DOI: 10.1016/j.lfs.2020.117331 Nada F Abo El-Magd 1 , Salma M Eraky 1
Life Sciences ( IF 5.2 ) Pub Date : 2020-01-20 , DOI: 10.1016/j.lfs.2020.117331 Nada F Abo El-Magd 1 , Salma M Eraky 1
Affiliation
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AIM
Drug-induced liver and kidney injuries are worldwide problems that cause restrictions in the use of drugs. The injury is highly mediated by oxidative stress and inflammation pathways. So, demonstrating the role of the natural compound (Vit.D) on the prevention of acetaminophen (APAP) overdose toxicity and the molecular mechanism through NrF2/BACH1/HO-1 pathway is promising.
EXPERIMENTAL
Male Sprague Dawley rats (40 rats) were divided randomly into 4 groups: Normal, APAP, APAP+Vit.D (500 IU/kg) and APAP+Vit.D (1000 IU/kg). The APAP toxicity caused by 2 g/kg (orally) on day 7.
KEY FINDINGS
Vit D decreased significantly liver and kidney functions: serum ALT and AST activities (P < 0.0005); creatinine and urea (P < 0.0005) concentrations; liver and kidney histopathological scores. Furthermore, Vit.D ameliorated APAP-caused oxidative stress through the liver malondialdehyde concentration's decrease and the total antioxidant capacity's increase (P < 0.0005). The molecular mechanism of Vit.D may include the prevention of high deteriorating increase of oxidative stress mediators: hepatic and renal NrF2 and BACH1 tissue expression in addition to serum HO-1 (P < 0.0005); the increase of inflammatory mediators; hepatic and renal NF-κB tissue expression, serum interleukin-10 (P < 0.0005) and TNF-α (P < 0.05). The 500 IU/kg Vit.D administration caused better protection results especially on the histopathological and immunohistochemical results than the 1000 IU/kg Vit.D administration.
SIGNIFICANCE
Vit.D ameliorates APAP-induced liver and kidney injury that may be attributed to its ability to moderately increase antioxidant status to counteract the toxicity without the massive destructive increase in the anti-oxidant pathway (NrF2/HO-1/BACH1). So, this work represents a great prophylactic role of Vit.D against drug-induced liver and kidney injury.
中文翻译：
强调了维生素D通过NrF2 / BACH1 / HO-1途径预防肝和肾急性毒性的分子机制。
目的药物引起的肝肾损伤是世界性的问题，导致药物使用受到限制。氧化应激和炎症途径是高度介导的损伤。因此，证明天然化合物（Vit.D）在预防对乙酰氨基酚（APAP）过量毒性中的作用以及通过NrF2 / BACH1 / HO-1途径的分子机制是有希望的。实验将雄性Sprague Dawley大鼠（40只大鼠）随机分为4组：正常，APAP，APAP + Vit.D（500IU / kg）和APAP + Vit.D（1000IU / kg）。第7天（口服）由2 g / kg引起的APAP毒性。主要发现Vit D显着降低了肝和肾功能：血清ALT和AST活性（P <0.0005）；肌酐和尿素浓度（P <0.0005）; 肝肾组织病理学评分。此外，Vit。D通过肝脏丙二醛浓度的降低和总抗氧化剂能力的提高来缓解APAP引起的氧化应激（P <0.0005）。Vit.D的分子机制可能包括防止氧化应激介质高度恶化的增加：除了血清HO-1外，肝和肾脏NrF2和BACH1组织的表达也升高（P <0.0005）；炎性介质的增加；肝和肾NF-κB组织表达，血清白细胞介素10（P <0.0005）和TNF-α（P <0.05）。与1000 IU / kg Vit.D给药相比，500 IU / kg Vit.D给药引起更好的保护效果，尤其是在组织病理学和免疫组织化学结果方面。意义Vit。D改善了APAP引起的肝脏和肾脏损伤，这可能归因于其适度增加抗氧化剂状态以抵消毒性而无需大量破坏性增加抗氧化剂途径（NrF2 / HO-1 / BACH1）的能力。因此，这项工作代表了Vit.D对药物性肝肾损害的巨大预防作用。
更新日期：2020-01-21
中文翻译：
强调了维生素D通过NrF2 / BACH1 / HO-1途径预防肝和肾急性毒性的分子机制。
目的药物引起的肝肾损伤是世界性的问题，导致药物使用受到限制。氧化应激和炎症途径是高度介导的损伤。因此，证明天然化合物（Vit.D）在预防对乙酰氨基酚（APAP）过量毒性中的作用以及通过NrF2 / BACH1 / HO-1途径的分子机制是有希望的。实验将雄性Sprague Dawley大鼠（40只大鼠）随机分为4组：正常，APAP，APAP + Vit.D（500IU / kg）和APAP + Vit.D（1000IU / kg）。第7天（口服）由2 g / kg引起的APAP毒性。主要发现Vit D显着降低了肝和肾功能：血清ALT和AST活性（P <0.0005）；肌酐和尿素浓度（P <0.0005）; 肝肾组织病理学评分。此外，Vit。D通过肝脏丙二醛浓度的降低和总抗氧化剂能力的提高来缓解APAP引起的氧化应激（P <0.0005）。Vit.D的分子机制可能包括防止氧化应激介质高度恶化的增加：除了血清HO-1外，肝和肾脏NrF2和BACH1组织的表达也升高（P <0.0005）；炎性介质的增加；肝和肾NF-κB组织表达，血清白细胞介素10（P <0.0005）和TNF-α（P <0.05）。与1000 IU / kg Vit.D给药相比，500 IU / kg Vit.D给药引起更好的保护效果，尤其是在组织病理学和免疫组织化学结果方面。意义Vit。D改善了APAP引起的肝脏和肾脏损伤，这可能归因于其适度增加抗氧化剂状态以抵消毒性而无需大量破坏性增加抗氧化剂途径（NrF2 / HO-1 / BACH1）的能力。因此，这项工作代表了Vit.D对药物性肝肾损害的巨大预防作用。
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