e9b45ea3a49f57b94c6abe49e6527893 antioxidants-12-02063-v3.pdf 0b92294053a7331ea5d26ae4eca16b382f4964e9 antioxidants-12-02063-v3.pdf f7938d22a79c5c1d13332fc7490f7864ffc24b78044a6379bdd0cce79deb7eda antioxidants-12-02063-v3.pdf Title: A Novel Therapy for Cisplatin-Induced Allodynia and Dysfunctional and Emotional Impairments in Male and Female Mice Subject: Patients undergoing chemotherapy with cisplatin (CIS) develop neuropathy in addition to other symptoms such as, anxiety, depression, muscle wasting and body weight loss. This symptomatology greatly weakens patients and may even lead to adjournment of chemotherapy. The protecting actions of molecular hydrogen in many neurological illnesses have been described, but its effect on the functional and emotional deficiencies caused by CIS has not been assessed. In C57BL/6J male and female mice injected with CIS, we examined the impact of the prophylactic treatment with hydrogen-rich water (HRW) on: (i) the tactile and cold allodynia, (ii) the deficits of grip strength and weight loss, (iii) the anxiodepressive-like behaviors and (iv) the inflammatory and oxidative reactions incited by CIS in the dorsal root ganglia (DRG) and prefrontal cortex (PFC). The results demonstrate that the mechanical allodynia and the anxiodepressive-like comportment provoked by CIS were similarly manifested in both sexes, whereas the cold allodynia, grip strength deficits and body weight loss produced by this chemotherapeutic agent were greater in female mice. Nonetheless, the prophylactic treatment with HRW prevented the allodynia and the functional and emotional impairments resulting from CIS in both sexes. This treatment also inhibited the inflammatory and oxidative responses activated by CIS in the DRG and PFC in both sexes, which might explain the therapeutic actions of HRW in male and female mice. In conclusion, this study revealed the plausible use of HRW as a new therapy for the allodynia and physical and mental impairments linked with CIS and its possible mechanism of action. Keywords: anxiety; chemotherapy-induced peripheral neuropathy; cisplatin; depression; hydrogen-rich water; inflammation; molecular hydrogen; oxidative stress Author: Ignacio Martínez-Martel and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 8 10:41:43 2023 CET ModDate: Fri Dec 8 10:45:27 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 9028321 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- KORLVE+VnURWPalladioL Type 1 Custom yes yes no 10 0 AFPFLL+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 XRXCOI+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 UVYASF+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 KESBIZ+EURM10 Type 1 Builtin yes yes no 68 0 WTAUCZ+CMSY10 Type 1 Builtin yes yes no 75 0 CIDFont+F3 CID TrueType Identity-H yes no yes 84 0 CIDFont+F2 CID TrueType Identity-H yes no yes 92 0 CIDFont+F1 CID TrueType Identity-H yes no yes 100 0 CIDFont+F3 CID TrueType Identity-H yes no yes 117 0 CIDFont+F2 CID TrueType Identity-H yes no yes 125 0 CIDFont+F1 CID TrueType Identity-H yes no yes 133 0 CIDFont+F3 CID TrueType Identity-H yes no yes 165 0 CIDFont+F2 CID TrueType Identity-H yes no yes 173 0 CIDFont+F1 CID TrueType Identity-H yes no yes 181 0 CIDFont+F3 CID TrueType Identity-H yes no yes 204 0 CIDFont+F2 CID TrueType Identity-H yes no yes 212 0 CIDFont+F1 CID TrueType Identity-H yes no yes 220 0 CIDFont+F3 CID TrueType Identity-H yes no yes 238 0 CIDFont+F2 CID TrueType Identity-H yes no yes 246 0 CIDFont+F1 CID TrueType Identity-H yes no yes 254 0 CIDFont+F3 CID TrueType Identity-H yes no yes 275 0 CIDFont+F2 CID TrueType Identity-H yes no yes 283 0 CIDFont+F1 CID TrueType Identity-H yes no yes 291 0 CIDFont+F3 CID TrueType Identity-H yes no yes 320 0 CIDFont+F2 CID TrueType Identity-H yes no yes 328 0 CIDFont+F1 CID TrueType Identity-H yes no yes 336 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-01-16 02:30:33 CET RepresentationInformation: antioxidants-12-02063-v3.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-01-10 01:35:51 CET Size: 9028321 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 666 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: Experimental Design Destination: subsection.2.2 Item: Title: Drug Administration Destination: subsection.2.3 Item: Title: Allodynia Destination: subsection.2.4 Item: Title: Forelimb Grip Strength Test Destination: subsection.2.5 Item: Title: Anxiety and Depressive Conducts Destination: subsection.2.6 Item: Title: Western Blot Destination: subsection.2.7 Item: Title: Statistical Analyses Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: The Prophylactic Treatment with HRW Inhibited the Mechanical and Cold Allodynia Generated by CIS in Male and Female Mice Destination: subsection.3.1 Item: Title: The Effects of the Prophylactic Treatment with HRW on the Grip Strength Deficits and Body Weight Loss Produced by CIS in Male and Female Mice Destination: subsection.3.2 Item: Title: Treatment with HRW Inhibited the Emotional Disorders Causes by CIS Destination: subsection.3.3 Item: Title: Effects of HRW on the Inflammatory and Oxidative Reactions Provoked by CIS in the DRG and PFC Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: A Novel Therapy for Cisplatin-Induced Allodynia and Dysfunctional and Emotional Impairments in Male and Female Mice Author: Ignacio Martínez-Martel and Olga Pol Subject: Patients undergoing chemotherapy with cisplatin (CIS) develop neuropathy in addition to other symptoms such as, anxiety, depression, muscle wasting and body weight loss. This symptomatology greatly weakens patients and may even lead to adjournment of chemotherapy. The protecting actions of molecular hydrogen in many neurological illnesses have been described, but its effect on the functional and emotional deficiencies caused by CIS has not been assessed. In C57BL/6J male and female mice injected with CIS, we examined the impact of the prophylactic treatment with hydrogen-rich water (HRW) on: (i) the tactile and cold allodynia, (ii) the deficits of grip strength and weight loss, (iii) the anxiodepressive-like behaviors and (iv) the inflammatory and oxidative reactions incited by CIS in the dorsal root ganglia (DRG) and prefrontal cortex (PFC). The results demonstrate that the mechanical allodynia and the anxiodepressive-like comportment provoked by CIS were similarly manifested in both sexes, whereas the cold allodynia, grip strength deficits and body weight loss produced by this chemotherapeutic agent were greater in female mice. Nonetheless, the prophylactic treatment with HRW prevented the allodynia and the functional and emotional impairments resulting from CIS in both sexes. This treatment also inhibited the inflammatory and oxidative responses activated by CIS in the DRG and PFC in both sexes, which might explain the therapeutic actions of HRW in male and female mice. In conclusion, this study revealed the plausible use of HRW as a new therapy for the allodynia and physical and mental impairments linked with CIS and its possible mechanism of action. 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