Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats

被引：7

作者：

Lucarini, Elena ^{[1
]}

Nocentini, Alessio ^{[2
]}

Bonardi, Alessandro ^{[2
]}

Chiaramonte, Niccolo ^{[2
]}

Parisio, Carmen ^{[1
]}

Micheli, Laura ^{[1
]}

Toti, Alessandra ^{[1
]}

Ferrara, Valentina ^{[1
]}

Carrino, Donatello ^{[3
]}

Pacini, Alessandra ^{[3
]}

Romanelli, Maria Novella ^{[2
]}

Supuran, Claudiu T. ^{[2
]}

Ghelardini, Carla ^{[1
]}

Mannelli, Lorenzo Di Cesare ^{[1
]}

机构：

[1] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Pharmacol & Toxicol Sect, Viale Gaetano Pieraccini 6, I-50139 Florence, Italy

[2] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Pharmaceut & Nutraceut Sci Sect, Via Ugo Schiff 6, I-50019 Florence, Italy

[3] Univ Florence, Dept Expt & Clin Med, Anat & Histol Sect, Largo Brambilla 3, I-50134 Florence, Italy

来源：

CELLS | 2021年 / 10卷 / 10期

关键词：

IBDs; visceral hypersensitivity; carbonic anhydrase IV; colon; inflammation; POTASSIUM-CHLORIDE-COTRANSPORTER; INFLAMMATORY-BOWEL-DISEASE; GASTROINTESTINAL-TRACT; ACETAZOLAMIDE; MOIETIES; CONTRIBUTES; EXPRESSION; MANAGEMENT; SYSTEM; VII;

D O I：

10.3390/cells10102540

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Persistent pain affecting patients with inflammatory bowel diseases (IBDs) is still very difficult to treat. Carbonic anhydrase (CA) represents an intriguing pharmacological target considering the anti-hyperalgesic efficacy displayed by CA inhibitors in both inflammatory and neuropathic pain models. The aim of this work was to evaluate the effect of inhibiting CA IV, particularly when expressed in the gut, on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) in rats. Visceral sensitivity was assessed by measuring animals' abdominal responses to colorectal distension. Repeated treatment with the selective CA IV inhibitors AB-118 and NIK-67 effectively counteracted the development of visceral pain induced by DNBS. In addition to pain relief, AB-118 showed a protective effect against colon damage. By contrast, the anti-hyperalgesic activity of NIK-67 was independent of colon healing, suggesting a direct protective effect of NIK-67 on visceral sensitivity. The enzymatic activity and the expression of CA IV resulted significantly increased after DNBS injection. NIK-67 normalised CA IV activity in DNBS animals, while AB-118 was partially effective. None of these compounds influenced CA IV expression through the colon. Although further investigations are needed to study the underlying mechanisms, CA IV inhibitors are promising candidates in the search for therapies to relieve visceral pain in IBDs.

引用

页数：16

共 55 条

[1] Benzensulfonamides bearing spyrohydantoin moieties act as potent inhibitors of human carbonic anhydrases II and VII and show neuropathic pain attenuating effects [J].