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In addition to hepatic toxicity, CYP and\/or ionizing gamma radiation (R) may impact the exocrine and endocrine functions of the pancreas. This study aims to determine whether sodium thiosulfate (STS) can protect male rats against CYP and\/or R-induced damage to the pancreas and liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Sixty-four rats were divided into eight groups, with STS administered for 14 days prior to CYP and\/or R treatment. Enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as insulin and glucose levels, were assessed. Amylase and lipase concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and malondialdehyde (MDA) levels were determined to evaluate lipid peroxidation. Glutathione content (GSH), glutathione-S-transferase (GST) activity, and reactive oxygen species (ROS) were quantified. Gene expression of extracellular signal-regulated kinase (Erk-1) and c-Jun N-terminal kinase (JNK) was analyzed using real-time quantitative polymerase chain reaction (qPCR). Histopathological examination and immunohistochemical staining with anti-nuclear factor erythroid 2-related factor 2 (anti-Nrf2) antibodies were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>STS treatment increased GSH, GST, and insulin levels while reducing ROS, MDA, glucose, amylase, and lipase levels. Furthermore, the STS treatment significantly downregulated mitogen-activated protein kinases (MAPKs) such as ERK and JNK Additionally, STS administration increased Nrf2 levels in both pancreatic and hepatic tissues while minimizing pathological changes. These findings suggest that STS may hold promise as a protective agent against CYP and\/or R-induced liver and pancreatic damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The ability of STS to enhance antioxidant defenses, reduce oxidative stress, modulate signaling pathways, and preserve tissue integrity suggests its therapeutic potential in mitigating the detrimental effects of these damaging conditions by inhibiting the MAPK, ERK, and JNK signaling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-025-01011-0","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:22:14Z","timestamp":1761729734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium thiosulfate (hydrogen sulfide donor) ameliorates the pancreatic and liver damage induced by cyclophosphamide and\/or ionizing gamma radiation in male albino rats"],"prefix":"10.1186","volume":"26","author":[{"given":"Ashraf","family":"Kassem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2337-688X","authenticated-orcid":false,"given":"Eman F. 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