Abstract
Laminitis is a serious health condition that causes severe pain and lameness in horses. Owing to our lack of understanding of laminitis, treatments often fail to achieve desired results. In recent years, we have recognized that laminitis may involve a complex interaction between local and systemic inflammation. Dysbiosis of the gut microbiota has been linked to the development of systemic inflammation, and our previous findings suggested that the development of laminitis is closely linked to the production of harmful metabolites in the gut microbiota. In addition, localized lesions in the hoof, especially lamellar injuries, are the most direct cause of laminitis. Metalloproteinases have been found to be strongly associated with the development of laminitis. A recent discovery found that Methylated Tirilazad (PTP-102) plays a role in repairing laminar tissues in vitro. However, its efficacy in horses has not been studied. Therefore, we aimed to investigate the efficacy of PTP-102 in the prevention and treatment of oligofructose-induced laminitis in horses. Twenty horses were randomly assigned to four groups: Control, Laminitis, Prophylactic (PTP-102 administered before laminitis induction), and Treatment (PTP-102 administered after laminitis induction). Samples were collected at the end of the study, 72 h after oligofructose administration. The results showed that oligofructose successfully induced laminitis in horses, resulting in detreated clinical signs. Blood serum indices (including inflammation-related and other related indices) were significantly increased. Dissection and staining showed significant bleeding, swelling, and damage to the hoof tissue. Analysis of the gut microbiota revealed a significant decrease in abundance and diversity and a significant increase in the relative abundance of specific bacteria. Following PTP-102 intervention, clinical signs, blood markers, and lamellar tissue damage improved significantly. PTP-102 also had an effect on the gut microbiota, especially those closely related to the development of laminitis. This may indicate that its therapeutic mechanism may be related to improvement of the gut microbiota in addition to direct anti-inflammatory activity. Notably, PTP-102 was more effective in the Treatment group than in the Prophylactic group, indicating that timing may be an important factor for laminitis management. These findings emphasize the therapeutic potential of PTP-102. Further studies are necessary to investigate the long-term effects of PTP-102.