misoprostol and Cystitis

Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A1 channels (TRPA1), which is modulated by the TRPA1 antagonist HC-030031. However, a few studies report the role of TRPA1 in visceral pain. Therefore, we investigated the participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels.. Mice were treated with vehicle or HC-030031 (18.75-300 mg/kg) before ifosfamide (400 mg/kg), 0.75% mustard oil (50 μL/colon), acetic acid 0.6% (10 mL/kg), zymosan (1 mg/cavity) or misoprostol (1 μg/cavity) injection. Visceral nociception was assessed through the electronic von Frey test or the writhing response. Ifosfamide-administered mice were euthanized for bladder analysis. The involvement of nitric oxide and the opioid system were investigated in mice injected with ifosfamide and mustard oil, respectively. The participation of resident peritoneal cells in acetic acid-, zymosan- or misoprostol-induced nociception was also evaluated.. HC-030031 failed to protect animals against ifosfamide-induced bladder injury (p > 0.05). However, a marked antinociceptive effect against ifosfamide, mustard oil, acetic acid, zymosan and misoprostol was observed (p < 0.05). Neither L-arginine (600 mg/kg) nor naloxone (2 mg/kg) could reverse the antinociceptive effect of HC-030031. The reduction of the peritoneal cell population inhibited the acetic acid and zymosan-related writhes without interfering with the misoprostol effect.. Our findings suggest that the blockade of TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.

Topics: Abdomen; Acetanilides; Animals; Antineoplastic Agents, Alkylating; Cell Count; Colitis; Cystitis; Dinoprostone; Endorphins; Ifosfamide; Inflammation; Male; Mice; Misoprostol; Motor Activity; Mustard Plant; Nitric Oxide; Nociception; Pain; Peritoneal Lavage; Physical Stimulation; Plant Oils; Purines; Transient Receptor Potential Channels; TRPA1 Cation Channel

A 15-year-old Quarter Horse gelding and a 26-year-old Thoroughbred gelding were evaluated because of hematuria of 4 to 6 days' duration following prolonged oral administration of phenylbutazone.. The horses had received either treatment with phenylbutazone for 3 months or intermittent long-term phenylbutazone treatment prior to development of hematuria. Each horse was systemically stable but had orthopedic or neurologic problems. Clinicopathologic findings included normochromic normocytic anemia in both horses and hypoalbuminemia and high BUN concentration in 1 horse. In both horses, urinalysis revealed proteinuria and RBCs, but no evidence of WBCs or bacteria. Ulceration and hemorrhage of the urinary bladder with no evidence of uroliths were observed via cystoscopy. Gastric ulceration along the margo plicatus was observed via gastroscopy.. For each horse, phenylbutazone treatment was discontinued and a synthetic prostaglandin (misoprostol) was administered. The hematuria resolved, and results of a follow-up CBC, serum biochemical analysis, urinalysis, and cystoscopy 25 or 30 days after cessation of phenylbutazone treatment were unremarkable in both cases.. Given the known adverse effects of NSAID treatment in several species, phenylbutazone and its metabolites were suspected to have caused ulceration of the urinary bladder, resulting in hematuria, in the 2 horses. A definitive cause of urinary bladder ulceration was not confirmed in these cases; however, resolution of ulceration after discontinuation of phenylbutazone treatment and administration of synthetic prostaglandins and exclusion of other causes suggested an association between phenylbutazone administration and ulcerative cystitis in these horses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cystitis; Hematuria; Horse Diseases; Horses; Male; Misoprostol; Omeprazole; Phenylbutazone; Ulcer

Direct instillation of drug solutions into the bladder through a urethral catheter (i.e., intravesical therapy) evades systemic adverse effects of drugs used for bladder diseases. However, conventional vehicles for these drugs fail to extend duration of drug exposure in the bladder beyond the first voiding of urine postinstillation. The current study seeks to overcome the aforementioned inherent limitation of intravesical drug administration by using thermosensitive hydrogel as a matrix for sustained intravesical drug delivery.. Under halothane anesthesia, normal adult female Sprague-Dawley rats were catheterized with PE-50 tubing to instill either 0.02% w/v solution of fluorescein isothiocyanate (FITC) or the same amount of FITC in a 30% w/v dispersion of thermosensitive [Poly(ethylene glycol)-Poly[lactic acid-co-glycolic acid]-Poly(ethylene glycol)) (PEG-PLGA-PEG) polymer in a 0.1 M phosphate buffer. After instillations, rats were kept in metabolic cages for urine collection. Fluorescence emanating from FITC was measured in the urine at various time points up to 24 h after instillation. A rat model of cyclophosphamide-induced cystitis was chosen for the efficacy study using misoprostol as a model drug entrapped in the thermosensitive hydrogel in place of FITC. Efficacy of hydrogel containing misoprostol was compared against rat groups instilled with saline, hydrogel, and misoprostol independently.. Prolonged drug exposure to the bladder afforded by hydrogel was evident from the time course of FITC elimination in the urine and by the green fluorescence of FITC seen at the bladder surface when isolated 24 h after instillation. Rats instilled with free FITC voided almost all of the fluorescence in the urine within the first 8 h, whereas rats instilled with hydrogel encapsulated FITC showed sustained release up to 24 h after instillation. Using a cyclophosphamide-induced cystitis model, rats instilled with misoprostol, a synthetic PGE1 analog, showed significantly reduced frequency of urine voiding (p < 0.05) as compared to the rats instilled with saline. Histological examination of the urothelium showed near normal morphology in rats instilled with misoprostol in hydrogel, whereas extensive tissue damage was observed in rats instilled with saline.. Our study showed that PEG-PLGA-PEG polymer could be used as a viable sustained drug delivery system for intravesical therapy of diseases of the bladder such as cystitis using misoprostol.

Topics: Animals; Cyclophosphamide; Cystitis; Delayed-Action Preparations; Drug Delivery Systems; Female; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Half-Life; Hydrogels; Injections; Misoprostol; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Stereoisomerism; Temperature; Urinary Bladder; Urinary Incontinence

Cyclophosphamide is a well established cytotoxic drug used in the treatment of lymphoproliferative disorders, certain solid tumors, and nonneoplastic disorders such as nephrotic syndrome, systemic lupus erythematosus and rheumatoid arthritis. Hemorrhagic cystitis can be a complication of this drug varying between two and 40 per cent. Misoprostol, which is a synthetic prostaglandin E1 analog, was found to significantly decrease the histological damage to the bladder from cyclophosphamide. Male rats receiving misoprostol in conjunction with cyclophosphamide were found to have a reduction in ulceration, inflammation and edema of the bladder walls as compared to those treated with cyclophosphamide alone.

Topics: Alprostadil; Animals; Cyclophosphamide; Cystitis; Hemorrhage; Male; Misoprostol; Mucous Membrane; Organ Size; Rats; Rats, Inbred Strains; Urinary Bladder; Urinary Bladder Diseases