RESUMO
Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires careful attention in veterinary practice. Malondialdehyde (MDA) is a serum biomarker associated with increased damage to the equine gastrointestinal system. This study investigated the hematological effects and alterations in the gastrointestinal tract and assessed serum MDA concentrations following repeated oral PBZ administration at clinical doses. Fourteen horses were randomly divided into control and treatment groups. All horses in the treatment group were administered 4.4 milligrams per kilogram of body weight of PBZ syrup orally twice a day for 7 days, whereas the control group received syrup as a placebo. The development of gastrointestinal side effects was investigated using gastroscopy, abdominal ultrasound, and fecal pH; serum MDA concentrations were assessed using a commercially available enzyme-linked immunosorbent assay kit. Data were compared between PBZ-treated and control horses before and after the treatment period. The treatment group exhibited decreased albumin and total protein concentrations. Moreover, this group exhibited a higher thickness of the right dorsal colon wall (p = 0.03) and had higher scores for squamous gastric ulcers (p = 0.01). Fecal pH was lower in the treatment group than in the control group after PBZ administration (p < 0.01). Although MDA concentrations were higher in the treatment group after PBZ administration, they did not differ significantly from those of the control group. This study highlighted the changes in hematological and gastrointestinal lesions resulting from PBZ administration in horses at clinical doses, even without clinical signs. However, MDA may not be an optimal biomarker for the early detection of gastrointestinal damage due to PBZ treatment in horses.
RESUMO
OBJECTIVE: Right dorsal colitis causes chronic colic associated with long-term treatment with nonsteroidal antiinflammatory drugs (NSAIDs). This study was designed to determine if NSAIDs could inhibit anion transporters that protect against intestinal mucosal injury in other species. ANIMALS: 20 healthy horses. METHODS: The effects of indomethacin (INDO) and firocoxib (FIR), on short-circuit current (Isc) in mucosa from the right dorsal colon (RDC) and right ventral colon (RVC) were measured in Ussing chambers by standard electrophysiological techniques. Immunohistochemical methods were used to detect apoptosis (caspase-3) with these NSAIDs and phenylbutazone (PBZ) and to locate the NKCC1 transporter. RESULTS: The Isc in RDC and RVC incubated with INDO or FIR was increased almost 3-fold (P < .0001) by prostaglandin E2 (PGE2) through a system inhibited by loop diuretics (P < .0001). Although these findings and anion replacement studies were consistent with anion secretion, the RDC also displayed an Isc response suggestive of a unique transporter apparently absent in RVC or NSAID-free solutions. In RDC, FIR, INDO, and PBZ induced apoptosis in the lower half of crypts. However, significant differences in apoptotic index were recorded in the RDC between NSAID-treated and control tissues (no NSAID). CLINICAL RELEVANCE: The effects of NSAIDs on Isc were consistent with reduced anion secretion, which could represent the pharmacological equivalent of the transport failure responsible for Cystic Fibrosis (CF) in other species. Failure of anion secretion could interfere with buffering acid from intraluminal fermentation, which could suggest a treatment target for right dorsal colitis.
