DOI: 10.1002/ame2.12559
Development and validation of BCG vaccine-induced novel granulomatous liver injury preclinical animal model
Swati Sharma1
Abhishek Moudgil2
Jyoti Grewal3
Pankaj Khatri4
Vishal Sharma5
Madhumita Premkumar6
Amanjit Bal7
Dibyajyoti Banerjee1
Amol N.Patil3
1.Department of Experimental Medicine and Biotechnology,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India2.Department of Internal Medicine,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India3.Department of Pharmacology,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India4.Department of Clinical Medicine and Medical Oncology,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India5.Department of Gastroenterology,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India6.Department of Hepatology,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India7.Department of Histopathology,Postgraduate Institute of Medical Education and Research(PGIMER),Chandigarh,India
摘要：Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs' metabolism in the presence of a spe-cific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus Calmette-Guérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.
Methods:We used 56 rats in seven equal groups.Group Ⅰ functioned as a normal control(NC)receiving normal saline only.Groups Ⅱ-Ⅳ received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21days.Groups Ⅴ,Ⅵ,and Ⅶreceived isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacri-ficed later for oxidative stress and histopathological examination.
Results:The study observed BCG dose-specific LFT derangements in groups Ⅱ-Ⅳcompared to group Ⅰ on day 21(p＜0.05).Isoniazid,rifampicin,and combination inter-vention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemi-cal changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9％in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).
Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.
机标关键词：developmentnovelmodelanimalgranulomatousinjuryliverpreclinical
论文发表日期：2025-03-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 930-938 )
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