19ed2101f253240b01b885bae65ad253 antioxidants-13-00856.pdf 402ed3139c632bc78629629d3c5e42489216efbe antioxidants-13-00856.pdf cb345ca0e2d2c1a99266aed966d96148b09ef79d998e9fa962cbacd7ddef9320 antioxidants-13-00856.pdf Title: The Combination of Molecular Hydrogen and Heme Oxygenase 1 Effectively Inhibits Neuropathy Caused by Paclitaxel in Mice Subject: Chemotherapy-provoked peripheral neuropathy and its associated affective disorders are important adverse effects in cancer patients, and its treatment is not completely resolved. A recent study reveals a positive interaction between molecular hydrogen (H2) and a heme oxygenase (HO-1) enzyme inducer, cobalt protoporphyrin IX (CoPP), in the inhibition of neuropathic pain provoked by nerve injury. Nevertheless, the efficacy of CoPP co-administered with hydrogen-rich water (HRW) on the allodynia and emotional disorders related to paclitaxel (PTX) administration has not yet been assessed. Using male C57BL/6 mice injected with PTX, we examined the effects of the co-administration of low doses of CoPP and HRW on mechanical and thermal allodynia and anxiodepressive-like behaviors triggered by PTX. Moreover, the impact of this combined treatment on the oxidative stress and inflammation caused by PTX in the amygdala (AMG) and dorsal root ganglia (DRG) were studied. Our results indicated that the antiallodynic actions of the co-administration of CoPP plus HRW are more rapid and higher than those given by each of them when independently administered. This combination inhibited anxiodepressive-like behaviors, the up-regulation of the inflammasome NLRP3 and 4-hydroxynonenal, as well as the high mRNA levels of some inflammatory mediators. This combination also increased the expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and/or the glutamate-cysteine ligase modifier subunit and decreased the protein levels of BACH1 in the DRG and/or AMG. Thus, it shows a positive interaction among HO-1 and H2 systems in controlling PTX-induced neuropathy by modulating inflammation and activating the antioxidant system. This study recommends the co-administration of CoPP plus HRW as an effective treatment for PTX-provoked neuropathy and its linked emotive deficits. Keywords: anxiety; depression; heme oxygenase 1; molecular hydrogen; neuropathy; oxidative stress; paclitaxel Author: Ignacio Martínez-Martel, Xue Bai, Rebecca Kordikowski, Christie R. A. Leite-Panissi and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Jul 17 10:12:21 2024 CEST ModDate: Wed Jul 17 10:19:56 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 8080885 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 TETFIN+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 OCUZIP+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 MGFBWM+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 NNKDOL+VnURWPalladioL Type 1 Custom yes yes yes 32 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 JPUAMM+EURM10 Type 1 Builtin yes yes yes 65 0 YFFKLH+CMSY10 Type 1 Builtin yes yes yes 73 0 MPUDFL+PazoMath Type 1 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Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 781 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Animals Destination: subsection.2.1 Item: Title: PTX-Derived Neuropathy Destination: subsection.2.2 Item: Title: Behavioral Tests Destination: subsection.2.3 Item: Title: Western Blot Analysis Destination: subsection.2.4 Item: Title: Analysis of mRNA Levels by Quantitative Real-Time PCR (qRT-PCR) Destination: subsection.2.5 Item: Title: Experimental Procedures Destination: subsection.2.6 Item: Title: Drugs Destination: subsection.2.7 Item: Title: Statistical Analyses Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: The Co-Treatment of CoPP with HRW Enhanced the Antiallodynic Effects Produced by Each Treatment Separately Destination: subsection.3.1 Item: Title: The Concurrent Administration of CoPP and HRW Normalized the Anxious- and Depressant-like Comportments Linked to PIPN Destination: subsection.3.2 Item: Title: The Effects of Combining CoPP with HRW on the Levels of NLRP3, 4-HNE, NRF2, HO-1, GSTM1, SOD-1, and BACH1 in the DRG and AMG of PTX-Injected Mice Destination: subsection.3.3 Item: Title: The Effects of CoPP Combined with HRW on the mRNA Levels of IL-1, IL-6, TNF, CGLC, and GCLM in the DRG and AMG of PTX-Injected Mice Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: The Combination of Molecular Hydrogen and Heme Oxygenase 1 Effectively Inhibits Neuropathy Caused by Paclitaxel in Mice Author: Ignacio Martínez-Martel, Xue Bai, Rebecca Kordikowski, Christie R. A. Leite-Panissi and Olga Pol Subject: Chemotherapy-provoked peripheral neuropathy and its associated affective disorders are important adverse effects in cancer patients, and its treatment is not completely resolved. A recent study reveals a positive interaction between molecular hydrogen (H2) and a heme oxygenase (HO-1) enzyme inducer, cobalt protoporphyrin IX (CoPP), in the inhibition of neuropathic pain provoked by nerve injury. Nevertheless, the efficacy of CoPP co-administered with hydrogen-rich water (HRW) on the allodynia and emotional disorders related to paclitaxel (PTX) administration has not yet been assessed. Using male C57BL/6 mice injected with PTX, we examined the effects of the co-administration of low doses of CoPP and HRW on mechanical and thermal allodynia and anxiodepressive-like behaviors triggered by PTX. Moreover, the impact of this combined treatment on the oxidative stress and inflammation caused by PTX in the amygdala (AMG) and dorsal root ganglia (DRG) were studied. Our results indicated that the antiallodynic actions of the co-administration of CoPP plus HRW are more rapid and higher than those given by each of them when independently administered. This combination inhibited anxiodepressive-like behaviors, the up-regulation of the inflammasome NLRP3 and 4-hydroxynonenal, as well as the high mRNA levels of some inflammatory mediators. This combination also increased the expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and/or the glutamate-cysteine ligase modifier subunit and decreased the protein levels of BACH1 in the DRG and/or AMG. Thus, it shows a positive interaction among HO-1 and H2 systems in controlling PTX-induced neuropathy by modulating inflammation and activating the antioxidant system. This study recommends the co-administration of CoPP plus HRW as an effective treatment for PTX-provoked neuropathy and its linked emotive deficits. 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