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.