{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T04:11:41Z","timestamp":1748405501227,"version":"3.41.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic\u2010TB (tuberculosis) and autoimmune granulomatous liver diseases. Antitubercular (ATT) and other drugs' metabolism in the presence of a specific 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\u2010Gu\u00e9rin) vaccine, further studying it in the presence of ATT dosing, and analyze the pharmacokinetics of isoniazid, rifampicin, and their respective primary metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used 56 rats in seven equal groups. Group I functioned as a normal control (NC) receiving normal saline only. Groups II\u2013IV received intravenous injections of low\u2010, medium\u2010, and high\u2010dose BCG vaccine daily for 21\u2009days. Groups V, VI, and VII received isoniazid (H) alone, rifampicin (R) alone, and isoniazid + rifampicin(HR) for a subsequent 15\u2009days 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 sacrificed later for oxidative stress and histopathological examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study observed BCG dose\u2010specific LFT derangements in groups II\u2013IV compared to group I on day 21 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Isoniazid, rifampicin, and combination intervention groups demonstrated normalization of the BCG\u2010led LFT changes. Histology and oxidative stress parameters confirmed model development and biochemical changes. Isoniazid area under the curve (AUC) showed a reduction of 16.9% in BCG\u2009+\u2009HR group in comparison to the BCG\u2009+\u2009H group (<jats:italic>p<\/jats:italic>\u2009=\u20090.01). Des\u2010acetyl\u2010rifampicin AUC and maximum\u2010concentration value demonstrated a significant rise in BCG\u2009+\u2009HR group in comparison to the BCG\u2009+\u2009R group (<jats:italic>p<\/jats:italic>\u2009=\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12559","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T11:25:24Z","timestamp":1739964324000},"page":"930-938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of <scp>BCG<\/scp> vaccine\u2010induced novel granulomatous liver injury preclinical animal model"],"prefix":"10.1002","volume":"8","author":[{"given":"Swati","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine and Biotechnology Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishek","family":"Moudgil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyoti","family":"Grewal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaj","family":"Khatri","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Medical Oncology Postgraduate Institute of Medical 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