β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation
Peripheral neuropathy is an important adverse effect caused by some chemotherapeutic agents, including oxaliplatin (OXA). OXA-induced peripheral neuropathy (OIPN) is a challenging condition due to diagnostic complexities and a lack of effective treatment. In this study, we investigated the antiallod...
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MDPI AG
2023-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/10/1893 |
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| author | Jonathan Paulo Agnes Barbara dos Santos Raquel Nascimento das Neves Vitória Maria Marques Luciano Larissa Benvenutti Fernanda Capitanio Goldoni Roberta Giusti Schran José Roberto Santin Nara Lins Meira Quintão Alfeu Zanotto-Filho |
| author_facet | Jonathan Paulo Agnes Barbara dos Santos Raquel Nascimento das Neves Vitória Maria Marques Luciano Larissa Benvenutti Fernanda Capitanio Goldoni Roberta Giusti Schran José Roberto Santin Nara Lins Meira Quintão Alfeu Zanotto-Filho |
| author_sort | Jonathan Paulo Agnes |
| collection | DOAJ |
| description | Peripheral neuropathy is an important adverse effect caused by some chemotherapeutic agents, including oxaliplatin (OXA). OXA-induced peripheral neuropathy (OIPN) is a challenging condition due to diagnostic complexities and a lack of effective treatment. In this study, we investigated the antiallodynic effect of β-caryophyllene (BCP), a cannabinoid type 2 (CB2) receptor agonist, in a mouse model of OIPN. BCP treatment inhibited OXA-induced mechanical and cold allodynia in both preventive and therapeutic drug treatment regimens. Experiments with the CB2 receptor agonist GW405833 confirmed the role of CB2 receptors in OIPN. The CB2 antagonist SR144528 abrogated the anti-nociceptive effect of BCP on mechanical allodynia, without impacting OXA-induced sensitivity to cold. BCP decreased neuroinflammation, as inferred from TNF, IL-1β, IL-6, and IL-10 profiling, and also reduced ROS production, lipid peroxidation, and 4-hydroxynonenal protein adduct formation in the spinal cords of OXA-treated mice. BCP did not affect the antitumor response to OXA or its impact on blood cell counts, implying that the cytotoxicity of OXA was preserved. These results underscore BCP as a candidate drug for OIPN treatment via CB2 receptor-dependent mechanisms, and anti-inflammatory and antioxidant responses in the spinal cord. |
| first_indexed | 2024-03-10T21:29:49Z |
| format | Article |
| id | doaj.art-dc3331dffa784fa0b46dabd9c88948bd |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T21:29:49Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-dc3331dffa784fa0b46dabd9c88948bd2023-11-19T15:28:40ZengMDPI AGAntioxidants2076-39212023-10-011210189310.3390/antiox12101893β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and NeuroinflammationJonathan Paulo Agnes0Barbara dos Santos1Raquel Nascimento das Neves2Vitória Maria Marques Luciano3Larissa Benvenutti4Fernanda Capitanio Goldoni5Roberta Giusti Schran6José Roberto Santin7Nara Lins Meira Quintão8Alfeu Zanotto-Filho9Department of Pharmacology, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, BrazilDepartment of Pharmacology, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, BrazilDepartment of Pharmacology, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, BrazilDepartment of Pharmacology, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, BrazilPostgraduate Program in Pharmaceutical Sciences, Universidade do Vale do Itajaí (UNIVALI), Itajaí 88302-901, BrazilPostgraduate Program in Pharmaceutical Sciences, Universidade do Vale do Itajaí (UNIVALI), Itajaí 88302-901, BrazilDepartment of Pharmacology, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, BrazilPostgraduate Program in Pharmaceutical Sciences, Universidade do Vale do Itajaí (UNIVALI), Itajaí 88302-901, BrazilPostgraduate Program in Pharmaceutical Sciences, Universidade do Vale do Itajaí (UNIVALI), Itajaí 88302-901, BrazilDepartment of Pharmacology, Universidade Federal de Santa Catarina (UFSC), Florianópolis 88040-900, BrazilPeripheral neuropathy is an important adverse effect caused by some chemotherapeutic agents, including oxaliplatin (OXA). OXA-induced peripheral neuropathy (OIPN) is a challenging condition due to diagnostic complexities and a lack of effective treatment. In this study, we investigated the antiallodynic effect of β-caryophyllene (BCP), a cannabinoid type 2 (CB2) receptor agonist, in a mouse model of OIPN. BCP treatment inhibited OXA-induced mechanical and cold allodynia in both preventive and therapeutic drug treatment regimens. Experiments with the CB2 receptor agonist GW405833 confirmed the role of CB2 receptors in OIPN. The CB2 antagonist SR144528 abrogated the anti-nociceptive effect of BCP on mechanical allodynia, without impacting OXA-induced sensitivity to cold. BCP decreased neuroinflammation, as inferred from TNF, IL-1β, IL-6, and IL-10 profiling, and also reduced ROS production, lipid peroxidation, and 4-hydroxynonenal protein adduct formation in the spinal cords of OXA-treated mice. BCP did not affect the antitumor response to OXA or its impact on blood cell counts, implying that the cytotoxicity of OXA was preserved. These results underscore BCP as a candidate drug for OIPN treatment via CB2 receptor-dependent mechanisms, and anti-inflammatory and antioxidant responses in the spinal cord.https://www.mdpi.com/2076-3921/12/10/1893oxaliplatinphytocannabinoidsneuropathic painoxidative stressneuroinflammation |
| spellingShingle | Jonathan Paulo Agnes Barbara dos Santos Raquel Nascimento das Neves Vitória Maria Marques Luciano Larissa Benvenutti Fernanda Capitanio Goldoni Roberta Giusti Schran José Roberto Santin Nara Lins Meira Quintão Alfeu Zanotto-Filho β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation Antioxidants oxaliplatin phytocannabinoids neuropathic pain oxidative stress neuroinflammation |
| title | β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation |
| title_full | β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation |
| title_fullStr | β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation |
| title_full_unstemmed | β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation |
| title_short | β-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation |
| title_sort | β caryophyllene inhibits oxaliplatin induced peripheral neuropathy in mice role of cannabinoid type 2 receptors oxidative stress and neuroinflammation |
| topic | oxaliplatin phytocannabinoids neuropathic pain oxidative stress neuroinflammation |
| url | https://www.mdpi.com/2076-3921/12/10/1893 |
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