The molecular mechanism underlining the preventive effect of vitamin D against hepatic and renal acute toxicity through the NrF2/ BACH1/ HO-1 pathway

Title : The molecular mechanism underlining the preventive effect of vitamin D against hepatic and renal acute toxicity through the NrF2/ BACH1/ HO-1 pathway

Abstract:

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 APAPcaused 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. With the current epidemic COVID-19,  the importance of Vit.D and acetaminophen had a great interest thus, may be combining them together will decrease the side effects of acetaminophen overdose.

Biography:

Nada Ghazy, lecturer of clinical biochemistry at Mansoura University, Egypt for 3 years. She worked as a post-doctoral fellowship visitor at Robert Gordon University, Aberdeen, the UK for 6 months starting from Jan 2019.  She got my B.Sc., M.Sc. and Ph.D of pharmaceutical sciences from Mansoura University, 2012, 2015 and 2018 respectively. She has a good experience in animal models and cell culture in addition to a good experience in several techniques like ELISA technique, colorimetric assay, RNA extraction, PCR work, gel electrophoresis, real-time PCR work, protein array, PCR array, and immunohistochemistry. She published 10 manuscripts in addition to 3 conference abstracts.