Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice
Cav3.2 T-type Ca2+ channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine), a medici...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-02-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315000079 |
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| author | Masahiro Murakami-Nakayama Maho Tsubota Saki Hiruma Fumiko Sekiguchi Kenji Matsuyama Takeshi Kimura Masahiro Moriyama Atsufumi Kawabata |
| author_facet | Masahiro Murakami-Nakayama Maho Tsubota Saki Hiruma Fumiko Sekiguchi Kenji Matsuyama Takeshi Kimura Masahiro Moriyama Atsufumi Kawabata |
| author_sort | Masahiro Murakami-Nakayama |
| collection | DOAJ |
| description | Cav3.2 T-type Ca2+ channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine), a medicine for peptic ulcer treatment and zinc supplementation, reveals preventive or therapeutic effects on bladder inflammation and/or pain in the mouse with cyclophosphamide-induced cystitis, a model for interstitial cystitis. Systemic administration of cyclophosphamide caused cystitis-related symptoms including increased bladder weight and vascular permeability, and histological signs of bladder edema, accompanied by bladder pain-like nociceptive behavior/referred hyperalgesia. All these symptoms were significantly attenuated by oral preadministration of polaprezinc at 400 mg/kg. The same dose of polaprezinc also prevented the increased malondialdehyde level, an indicator of lipid peroxidation, and protein upregulation of cystathionine-γ-lyase, an H2S-generating enzyme, but not occludin, a tight junction-related membrane protein, in the bladder tissue of cyclophosphamide-treated mice. Oral posttreatment with polaprezinc at 30–100 mg/kg reversed the nociceptive behavior/referred hyperalgesia in a dose-dependent manner without affecting the increased bladder weight. Together, our data show that zinc supplementation with polaprezinc prevents the cyclophosphamide-induced cystitis probably through the antioxidant activity, and, like T-channel blockers, reverses the established cystitis-related bladder pain in mice, suggesting novel therapeutic usefulness of polaprezinc. |
| first_indexed | 2024-04-12T11:43:42Z |
| format | Article |
| id | doaj.art-236eed3ecf8b4c87a39340faba505b90 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T11:43:42Z |
| publishDate | 2015-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-236eed3ecf8b4c87a39340faba505b902022-12-22T03:34:28ZengElsevierJournal of Pharmacological Sciences1347-86132015-02-01127222322810.1016/j.jphs.2015.01.004Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in miceMasahiro Murakami-Nakayama0Maho Tsubota1Saki Hiruma2Fumiko Sekiguchi3Kenji Matsuyama4Takeshi Kimura5Masahiro Moriyama6Atsufumi Kawabata7Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka 577-8502, JapanDivision of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka 577-8502, JapanDivision of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka 577-8502, JapanDivision of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka 577-8502, JapanDivision of Clinical Pharmacy, Kinki University School of Pharmacy, Higashi-Osaka 577-8502, JapanDepartment of Pharmacy, Hyogo College of Medicine Hospital, Nishinomiya 663-8501, JapanSection of Clinical Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, JapanDivision of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka 577-8502, JapanCav3.2 T-type Ca2+ channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine), a medicine for peptic ulcer treatment and zinc supplementation, reveals preventive or therapeutic effects on bladder inflammation and/or pain in the mouse with cyclophosphamide-induced cystitis, a model for interstitial cystitis. Systemic administration of cyclophosphamide caused cystitis-related symptoms including increased bladder weight and vascular permeability, and histological signs of bladder edema, accompanied by bladder pain-like nociceptive behavior/referred hyperalgesia. All these symptoms were significantly attenuated by oral preadministration of polaprezinc at 400 mg/kg. The same dose of polaprezinc also prevented the increased malondialdehyde level, an indicator of lipid peroxidation, and protein upregulation of cystathionine-γ-lyase, an H2S-generating enzyme, but not occludin, a tight junction-related membrane protein, in the bladder tissue of cyclophosphamide-treated mice. Oral posttreatment with polaprezinc at 30–100 mg/kg reversed the nociceptive behavior/referred hyperalgesia in a dose-dependent manner without affecting the increased bladder weight. Together, our data show that zinc supplementation with polaprezinc prevents the cyclophosphamide-induced cystitis probably through the antioxidant activity, and, like T-channel blockers, reverses the established cystitis-related bladder pain in mice, suggesting novel therapeutic usefulness of polaprezinc.http://www.sciencedirect.com/science/article/pii/S1347861315000079PolaprezincCyclophosphamide-induced cystitisBladder painT-type Ca2+ channelAntioxidant activity |
| spellingShingle | Masahiro Murakami-Nakayama Maho Tsubota Saki Hiruma Fumiko Sekiguchi Kenji Matsuyama Takeshi Kimura Masahiro Moriyama Atsufumi Kawabata Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice Journal of Pharmacological Sciences Polaprezinc Cyclophosphamide-induced cystitis Bladder pain T-type Ca2+ channel Antioxidant activity |
| title | Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice |
| title_full | Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice |
| title_fullStr | Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice |
| title_full_unstemmed | Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice |
| title_short | Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice |
| title_sort | polaprezinc attenuates cyclophosphamide induced cystitis and related bladder pain in mice |
| topic | Polaprezinc Cyclophosphamide-induced cystitis Bladder pain T-type Ca2+ channel Antioxidant activity |
| url | http://www.sciencedirect.com/science/article/pii/S1347861315000079 |
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