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

Lucarini, Elena; Nocentini, Alessio; Bonardi, Alessandro; Chiaramonte, Niccolò; Parisio, Carmen; Micheli, Laura; Toti, Alessandra; Ferrara, Valentina; Carrino, Donatello; Pacini, Alessandra; Romanelli, Maria Novella; Ghelardini, Carla; Mannelli, Lorenzo Di Cesare

doi:10.3390/cells10102540

Cited by 4 publications

(5 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous works have highlighted the active role of several carbonic anhydrase inhibitors (CAIs) in reducing different pain states in preclinical settings. CAIs’ efficacy against rheumatoid arthritis has emerged [ 9 , 10 , 11 ] as well as against visceral pain, and in this experiment, the CAI IV isoform has been revealed as the main actor to counteract the development of colitis in rats [ 12 ]. Moving to neuropathies induced by chemotherapeutic drugs, CAIs have been observed to possess anti-neuropathic properties in particular against oxaliplatin-induced neurotoxicity [ 13 , 14 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…Recent discoveries, aimed to identify and characterize new therapeutic strategies, have highlighted the inhibition of carbonic anhydrase (CA) as a new valid approach for pain management [ 8 ]. Carbonic anhydrase inhibitors (CAIs) have been shown to possess pain-relieving properties against inflammatory pain resembling human rheumatoid arthritis [ 9 , 10 , 11 ] against persistent visceral pain, in which the CA IV isoform is particularly involved, [ 12 ] as well as against oxaliplatin-induced pain threshold alterations [ 13 , 14 ]. CAs are a ubiquitous superfamily of enzymes that catalyze a reaction fundamental for life: the hydration of CO 2 to bicarbonate and protons.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Micheli

Testai

Angeli

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca2+ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Micheli

Testai

Angeli

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…At the end of the experiment, the sensitivity and visceral pain caused by colitis were evaluated using three different methodologies such as Von Frey, VMR, and AWR tests. We followed all the steps based on previous studies [ 37 , 38 , 39 ] and they are briefly described below. Hypersensitivity to abdominal pain has been evaluated by the von Frey test, which consists of a force detector equipped with a plastic tip [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

“…A score 0 means that no behavioral response has been observed, score 1 means that the animal remained motionless during distension in the colon or had some occasional movement, score 2 means that a weak abdominal contraction was observed, score 3 means that a strong abdominal contraction was observed, and score 4 means that the animal had violent contractions of the body and abdomen [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

New Insights into the Mechanism of Ulva pertusa on Colitis in Mice: Modulation of the Pain and Immune System

et al. 2023

View full text Add to dashboard Cite

Inflammatory bowel diseases (IBDs) involving Crohn’s disease (CD) and ulcerative colitis (UC) are gastrointestinal (GI) disorders in which abdominal pain, discomfort, and diarrhea are the major symptoms. The immune system plays an important role in the pathogenesis of IBD and, as indicated by several clinical studies, both innate and adaptative immune response has the faculty to induce gut inflammation in UC patients. An inappropriate mucosal immune response to normal intestinal constituents is a main feature of UC, thus leading to an imbalance in local pro- and anti-inflammatory species. Ulva pertusa, a marine green alga, is known for its important biological properties, which could represent a source of beneficial effects in various human pathologies. We have already demonstrated the anti-inflammatory, antioxidant, and antiapoptotic effects of an Ulva pertusa extract in a murine model of colitis. In this study, we aimed to examine thoroughly Ulva pertusa immunomodulatory and pain-relieving properties. Colitis was induced by using the DNBS model (4 mg in 100 μL of 50% ethanol), whereas Ulva pertusa was administered daily at the dosage of 50 and 100 mg/kg by oral gavage. Ulva pertusa treatments have been shown to relieve abdominal pain while modulating innate and adaptative immune-inflammatory responses. This powerful immunomodulatory activity was specifically linked with TLR4 and NLRP3 inflammasome modulation. In conclusion, our data suggest Ulva pertusa as a valid approach to counteract immune dysregulation and abdominal discomfort in IBD.

show abstract

“…For abdominal withdrawal response (AWR) we used the method indicated by Lucarini et al [ 25 ], through a semi-quantitative score.…”

Section: Methodsmentioning

confidence: 99%

A Combination of Xyloglucan, Pea Protein and Chia Seed Ameliorates Intestinal Barrier Integrity and Mucosa Functionality in a Rat Model of Constipation-Predominant Irritable Bowel Syndrome

Filippone

Ardizzone

Bova

et al. 2022

JCM

View full text Add to dashboard Cite

Irritable Bowel Syndrome is a gastrointestinal disorder that affects the large intestine, which encompasses several symptoms including, but not limited to, abdominal pain, bloating and dysmotility. In particular, IBS associated with constipation (IBS-C) is characterized by hard and dry stools and inadequate evacuation and difficulty in defecation. Although several drugs ameliorate intestinal modifications and constipation-associated features, management of IBS is still a challenge. Natural compounds including Xyloglucan and pea protein (XP) and Chia seed powder (CS) are widely known to possess beneficial effects in counteracting several gastrointestinal disorders. Here, we aimed to assess the combined effects of XP and CS to treat constipation-related alterations in an IBS-C rat model. IBS-C was induced by gastric instillation of 2 mL of cold water (0–4 °C) for 14 days and Xiloglucan, Pea protein and Chia seeds (XP + CS) treatment was orally administered for 7 days. On day 22, colon tissues were collected for histological analysis. Our results showed that XP + CS administration attenuated constipation-related parameters by increasing body weight and food and water intake. Upon XP + CS treatment, from day 14 to 22, stool moisture content was restored to physiological level. Colonic tissues from IBS-C rats depicted a disruption of the organ architecture accompanied by edema. Loss of colonic structure was reflected by the marked reduction of tight junction protein expression, Occludin and zona occludens-1 (ZO-1). Administration of XP + CS treatment in IBS-C rats significantly ameliorated the colonic histological parameters and exerted a positive effect on barrier integrity by restoring the expression of Occludin and zona occludens-1 (ZO-1). Our findings demonstrated that the efficacy of XP and CS in managing constipation in rats is due to the ability of these compounds to form a protective barrier fortifying intestinal integrity and gut functionality.

show abstract

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

Cited by 4 publications

References 53 publications

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

New Insights into the Mechanism of Ulva pertusa on Colitis in Mice: Modulation of the Pain and Immune System

A Combination of Xyloglucan, Pea Protein and Chia Seed Ameliorates Intestinal Barrier Integrity and Mucosa Functionality in a Rat Model of Constipation-Predominant Irritable Bowel Syndrome

Contact Info

Product

Resources

About