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Cytotoxicity of olsalazine, gemcitabine, and combination was measured on human HePG2 cells using MTT assay. Anti\u2010tumor effects of the combination were assessed using animal model of N\u2010nitrosodiethylamine and carbon tetrachloride\u2010induced HCC. Treatment was initiated from 8th week of induction to 11th week and changes in body weight, liver weight (absolute and relative), and survival rate were measured. Following treatment, blood samples were collected for estimation of serum biochemistry. Blood serum was used for the estimation of inflammatory cytokines: tumor necrosis factor\u2010\u03b1\u00a0(TNF\u2010\u03b1), interleukin\u20106 (IL\u20106), C\u2010reactive protein\u00a0[CRP],\u00a0lactate dehydrogenase (LDH), and P53 levels. Oxidative stress markers were measured in liver tissue homogenates. Histopathology and immunohistochemistry (IHC) were performed on liver sections to detect the morphological changes and P53 expression. Docking analysis revealed the interactions between olsalazine and DNMT1 with a binding energy score of \u22125.34 and gemcitabine and DNA with a binding energy score of \u22125.93. Olsalazine pretreatment potentiated the anticancer effects of gemcitabine in cell line study. In the groups receiving olsalazine pretreatment showed significant reductions in relative liver weight and improved survival rate. Serum biochemical markers:\u00a0serum glutamate pyruvate transaminase,\u00a0serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin revealed improved liver functions. Olsalazine pretreatment also reduced the levels of inflammatory markers: CRP, LDH, TNF\u2010\u03b1, and IL\u20106 and oxidative stress markers dose dependently. Histopathology and IHC showed improved liver morphology with potentiated induction of P53 upon olsalazine pretreatment in combination with gemcitabine. In conclusion, sequential combination of olsalazine and gemcitabine improved\u00a0the treatment outcomes during the progression of HCC.<\/jats:p>","DOI":"10.1002\/jbt.23737","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T08:00:50Z","timestamp":1716796850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Olsalazine pretreatment augments chemosensitivity of gemcitabine in hepatocellular carcinoma"],"prefix":"10.1002","volume":"38","author":[{"given":"Ayush","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Pharmacy, Nirma University  Ahmedabad Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1208-1162","authenticated-orcid":false,"given":"Abu Sufiyan","family":"Chhipa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Pharmacy, Nirma University  Ahmedabad Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srashti","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Pharmacy, Nirma University  Ahmedabad Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palak","family":"Parikh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry and Quality Assurance L. 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