Pirfenidone inhibits cryoablation induced local macrophage infiltration along with its associated TGFb1 expression and serum cytokine level in a mouse model |
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Institution: | 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, H-118, New York, NY 10065, USA;2. Microinvasive Interventional Department, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China;3. Clinical and Translational Science Center, Weill Cornell Medicine, New York, NY 10065, USA;1. Department of Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt;2. Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt;3. Department of Animal Wealth Development, Genetics and Genetic Engineering, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt;4. Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt;1. Department of Radiology, Mie University School of Medicine, Tsu, Mie, Japan;2. Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan;1. Department of Thoracic Surgery, Hôpital Nord–APHM, Aix-Marseille University, Marseille, France;2. Center of Radiology, Aubagne, France;3. Department of Gynecology and Obstetrics, Hôpital Nord–APHM, Aix-Marseille University, Marseille, France;1. Department of Neurosurgery, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, Fujian 364000, China;2. Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China;3. Department of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China |
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Abstract: | PurposeTo investigate the effects of pirfenidone (PFD) on post-cryoablation inflammation in a mouse model.Materials and methodsIn this IACUC-approved study, eighty Balb/c mice were randomly divided into four groups (20/group): sham + vehicle, sham + PFD, cryoablation + vehicle, and cryoablation + PFD. For cryoablation groups, a 20% freeze rate cryoablation (20 s to less than ?100 °C) was used to ablate normal muscle in the right flank. For sham groups, the cryoprobe was advanced into the flank and maintained for 20 s without ablation. PFD or vehicle solution was intraperitoneally injected (5 mg/kg) at days 0, 1, 2, 3, and then every other day until day 13 after cryoablation. Mice were euthanized at days 1, 3, 7, and 14. Blood samples were used for serum IL-6, IL-10, and TGFβ1 analysis using electrochemiluminescence and ELISA assays, respectively. Immunohistochemistry-stained ablated tissues were used to analyze macrophage infiltration and local TGFβ1 expression in the border region surrounding the cryoablation-induced coagulation zone.ResultsCryoablation induced macrophage infiltration and increased TGFβ1 expression in the border of the necrotic zone, and high levels of serum IL-6, peaking at days 7 (70.5 ± 8.46/HPF), 14 (228 ± 18.36/HPF), and 7 (298.67 ± 92.63), respectively. Animals receiving PFD showed reduced macrophage infiltration (35.5 ± 16.93/HPF at day 7, p < 0.01) and cytokine levels (60.2 ± 7.6/HPF at day 14, p < 0.01). PFD also significantly reduced serum IL-6 levels (p < 0.001 vs. all non-PFD groups).ConclusionsPFD mitigates cryoablation induced muscle tissue macrophage infiltration, increased IL-6 levels, and local TGFβ1 expression in a small animal model. |
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Keywords: | Cryoablation Macrophage IL-6 TGFβ1 Pirfenidone BSA"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"bovine serum albumin CA"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"Cryoablation DMSO"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"dimethyl sulfoxide ELISA"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"enzyme-linked immunosorbent assay HGF"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"hepatocyte growth factor HPF"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"high-power field IACUC"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"institutional animal care and use committee IHC"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"immunohistochemistry PEG"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"polyethylene glycol PFD"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"pirfenidone |
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