The M1/M2 Macrophage Polarization and Hepatoprotective Activity of Quercetin in Cyclophosphamide-Induced Experimental Liver Toxicity

被引:0
作者
Seker, Ugur [1 ]
Uyar, Emre [2 ]
Gokdemir, Gul Sahika [3 ]
Kavak, Deniz Evrim [4 ]
Irtegun-Kandemir, Sevgi [5 ]
机构
[1] Mardin Artuklu Univ, Fac Med, Dept Histol & Embryol, Mardin, Turkiye
[2] Uskudar Univ, Fac Med, Dept Med Pharmacol, Istanbul, Turkiye
[3] Mardin Artuklu Univ, Fac Med, Dept Physiol, Mardin, Turkiye
[4] Dokuz Eylul Univ, Fac Med, Dept Med Biol & Genet, Izmir, Turkiye
[5] Dicle Univ, Fac Med, Dept Med Biol, Diyarbakir, Turkiye
关键词
apoptosis; cyclophosphamide; inflammation; liver toxicity; quercetin; INDUCED HEPATOTOXICITY; INDUCED CARDIOTOXICITY; OXIDATIVE STRESS; VITAMIN-E; DOXORUBICIN; KIDNEY;
D O I
10.1002/vms3.70183
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Background: Chemotherapy drugs may lead to hepatic injury, which is considered one of the limitations of these drugs. Objectives: The aim of this study was to evaluate the effect of quercetin (QUE) on M1/M2 macrophage polarization and hepatoprotective effect in cyclophosphamide (CTX)-induced liver toxicity. Methods: Twenty-four mice were divided into four groups (Control, QUE, CTX, CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg CTX. The animals in the QUE and CTX + QUE groups received 50 mg/kg QUE. All animals were sacrificed, and serum and liver samples were used for laboratory analyses. Results: Examinations indicated that CTX exposure led to disruption of liver functions and morphological degenerations. Tissue pro-apoptotic Bax and caspase 3, pro-inflammatory TNF-alpha and IL-1 beta, transcription factor NF-kappa B, and M1 macrophage polarization marker CD86 were upregulated significant (p < 0.05) in this group. In addition, CTX exposure led to significantly (p < 0.05) upregulation of the Bax/Bcl-2 mRNA ratio and DNA fragmentations. The PCNA-positive hepatic cell ratio and anti-apoptotic Bcl-2 expression are remarkably suppressed (p < 0.05). Immunohistochemical analyses are also indicated that M2 macrophage polarization marker CD163 is slightly but remarkably (p < 0.05) downregulated in the CTX group compared to the Control and QUE groups. The morphological and biochemical disruptions were alleviated in QUE-treated animals in the CTX + QUE group. Liver function test results, apoptosis, inflammatory, transcription factor NF-kappa B, regeneration/proliferation, and apoptotic index results in this group were similar (p > 0.05) to the control and QUE groups. The M1 cell surface marker expression of CD86 is significantly (p < 0.05) downregulated, and M2 macrophage polarization marker expression of CD163 is upregulated significantly (p < 0.05) compared to the CTX group. Conclusions: This study indicates that QUE has the potential to downregulate CTX-induced hepatic injury and regulate M1/M2 macrophage polarization to the M2 side, which indirectly demonstrates activation of anti-inflammatory signalling and tissue repair.
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页数:10
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