{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:49:27Z","timestamp":1790772567203,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp;amp; Sci"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chemotherapy drugs may lead to hepatic injury, which is considered one of the limitations of these drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The aim of this study was to evaluate the effect of quercetin (QUE) on M1\/M2 macrophage polarization and hepatoprotective effect in cyclophosphamide (CTX)\u2010induced liver toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty\u2010four mice were divided into four groups (Control, QUE, CTX, CTX + QUE). The CTX and CTX + QUE groups received 200\u00a0mg\/kg CTX. The animals in the QUE and CTX + QUE groups received 50\u00a0mg\/kg QUE. All animals were sacrificed, and serum and liver samples were used for laboratory analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Examinations indicated that CTX exposure led to disruption of liver functions and morphological degenerations. Tissue pro\u2010apoptotic Bax and caspase 3, pro\u2010inflammatory TNF\u2010\u03b1 and IL\u20101\u03b2, transcription factor NF\u2010\u03baB, and M1 macrophage polarization marker CD86 were upregulated significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) in this group. In addition, CTX exposure led to significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) upregulation of the Bax\/Bcl\u20102 mRNA ratio and DNA fragmentations. The PCNA\u2010positive hepatic cell ratio and anti\u2010apoptotic Bcl\u20102 expression are remarkably suppressed (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Immunohistochemical analyses are also indicated that M2 macrophage polarization marker CD163 is slightly but remarkably (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) downregulated in the CTX group compared to the Control and QUE groups. The morphological and biochemical disruptions were alleviated in QUE\u2010treated animals in the CTX + QUE group. Liver function test results, apoptosis, inflammatory, transcription factor NF\u2010\u03baB, regeneration\/proliferation, and apoptotic index results in this group were similar (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&gt;\u00a00.05) to the control and QUE groups. The M1 cell surface marker expression of CD86 is significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) downregulated, and M2 macrophage polarization marker expression of CD163 is upregulated significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) compared to the CTX group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study indicates that QUE has the potential to downregulate CTX\u2010induced hepatic injury and regulate M1\/M2 macrophage polarization to the M2 side, which indirectly demonstrates activation of anti\u2010inflammatory signalling and tissue repair.<\/jats:p>\n                  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