TY - JOUR
T1 - Inflammatory markers S100A8/A9 and metabolic alteration for evaluating signs of early phase toxicity of anticancer agent treatment
AU - Morikawa-Ichinose, Tomomi
AU - Fujimura, Yoshinori
AU - Kumazoe, Motofumi
AU - Onda, Hiroaki
AU - Miura, Daisuke
AU - Tachibana, Hirofumi
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grant Numbers JP20H05683 (to H.T.), JP20H02935 and JP22K19154 (to Y.F.), and JP22K05525 (to T.M-I.). The LCMS-8050 analysis was performed at the Center for Advanced Instrumental and Educational Supports, Faculty of Agriculture, Kyushu University. We appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. We would like to thank Editage (www.editage.com) for English language editing.
Funding Information:
This work was supported in part by JSPS KAKENHI Grant Numbers JP20H05683 (to H.T.), JP20H02935 and JP22K19154 (to Y.F.), and JP22K05525 (to T.M-I.). The LCMS-8050 analysis was performed at the Center for Advanced Instrumental and Educational Supports, Faculty of Agriculture, Kyushu University. We appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. We would like to thank Editage ( www.editage.com ) for English language editing.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/11
Y1 - 2022/11
N2 - Anticancer agents can cause various side effects, including tissue damages/inflammatory reactions. Drug-responsive biomarkers are essential for evaluating drug toxicity in disease processes. S100 calcium-binding proteins A8/A9 (S100A8/A9) are highly expressed in neutrophils and monocytes/macrophages accumulated at inflammatory sites and are known to be related to tissue damage/inflammation; however, their response to drug toxicity has not been reported. Herein, we investigated the effects of anticancer agents (doxorubicin, cisplatin, and docetaxel) on S100A8/A9 gene expression profiles in four representative tissues (heart, kidney, liver, and lung) in normal C57BL/6J mice. Both S100A8/A9 expression was transiently or time-dependently elevated in four tissues within 48 h after dosing of the three anticancer agents under toxicity-inducing conditions. S100A8/A9 patterns differed among agents and tissues. This result suggests that S100A8/A9 is useful for evaluating anticancer agent-induced tissue damage. Metabolomic analysis revealed that some metabolites showed temporal patterns similar to that of S100A8/A9 expression. The amounts of fumarate (doxorubicin-treated heart), tyrosine (cisplatin-treated kidney), acetylcarnosine (doxorubicin-treated liver), and 2-phosphoglycerate (docetaxel-treated lung) showed similar patterns to that of S100A8/A9 expression. Although these metabolites showed different behaviors between tissues and serum, they may be useful marker candidates for evaluating anticancer agent-induced tissue damage at an earlier stage after dosing.
AB - Anticancer agents can cause various side effects, including tissue damages/inflammatory reactions. Drug-responsive biomarkers are essential for evaluating drug toxicity in disease processes. S100 calcium-binding proteins A8/A9 (S100A8/A9) are highly expressed in neutrophils and monocytes/macrophages accumulated at inflammatory sites and are known to be related to tissue damage/inflammation; however, their response to drug toxicity has not been reported. Herein, we investigated the effects of anticancer agents (doxorubicin, cisplatin, and docetaxel) on S100A8/A9 gene expression profiles in four representative tissues (heart, kidney, liver, and lung) in normal C57BL/6J mice. Both S100A8/A9 expression was transiently or time-dependently elevated in four tissues within 48 h after dosing of the three anticancer agents under toxicity-inducing conditions. S100A8/A9 patterns differed among agents and tissues. This result suggests that S100A8/A9 is useful for evaluating anticancer agent-induced tissue damage. Metabolomic analysis revealed that some metabolites showed temporal patterns similar to that of S100A8/A9 expression. The amounts of fumarate (doxorubicin-treated heart), tyrosine (cisplatin-treated kidney), acetylcarnosine (doxorubicin-treated liver), and 2-phosphoglycerate (docetaxel-treated lung) showed similar patterns to that of S100A8/A9 expression. Although these metabolites showed different behaviors between tissues and serum, they may be useful marker candidates for evaluating anticancer agent-induced tissue damage at an earlier stage after dosing.
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U2 - 10.1016/j.fct.2022.113421
DO - 10.1016/j.fct.2022.113421
M3 - Article
C2 - 36100043
AN - SCOPUS:85138061926
SN - 0278-6915
VL - 169
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
M1 - 113421
ER -