MMP-2 Plays an Important Role During the Early Acute Developmental Phase of Oligofructose-Induced Equine Laminitis

Li, Xinran; Jiang, Renli; Wang, Guanying; Li, Yue; Fan, Xiaojing; Liu, Xu; Wang, Jinglu; Pan, Jialiang; Li, Gao

doi:10.1515/bvip-2015-0022

Cited by 5 publications

References 29 publications

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High-grain diet feeding altered the composition and functions of the rumen bacterial community and caused the damage to the laminar tissues of goats

Zhang

Jin

Feng

et al. 2018

Animal

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In the current intensive production system, ruminants are often fed high-grain (HG) diets. However, this feeding pattern often causes rumen metabolic disorders and may further trigger laminitis, the exact mechanism is not clear. This study investigated the effect of HG diet feeding on fermentative and microbial changes in the rumen and on the expression of pro-inflammatory cytokines and matrix metalloproteinases (MMPs) in the lamellar tissue. In all, 12 male goats were fed a hay diet (0% grain; n=6) or an HG diet (56.5% grain; n=6). On day 50 of treatment, samples of blood, rumen content, and lamellar tissue of hooves of goats were collected. The data showed that compared with the hay group, HG-fed goats had lower (P<0.05) rumen pH but higher (P<0.05) total volatile fatty acids and lactate in the rumen and higher (P<0.05) lipopolysaccharide (LPS) levels in the rumen and blood. HG diet feeding altered the composition of rumen bacterial community, and correspondingly, the results suggested that their functions in the HG group were also altered. HG diet feeding increased (P<0.05) the expression of interleukin-1β, interleukin-6, tumour necrosis factor-α and MMP-2 mRNA in the lamellar tissues compared with the hay group. Correlation analysis indicated that the expression of pro-inflammatory cytokines were positively correlated with MMP-2 expression in lamellar tissues. Overall, these results revealed that HG feeding altered the patterns of rumen fermentation and the composition and functions of rumen bacterial community, and lead to higher levels of LPS in the peripheral blood, and further activated the inflammatory response in lamellar tissues, which may progress to the level of laminar damage.

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High-grain diet feeding altered the composition and functions of the rumen bacterial community and caused the damage to the laminar tissues of goats

Zhang

Jin

Feng

et al. 2018

Animal

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Methylated Tirilazad (PTP-102) May Mitigate Oligofructose-Induced Laminitis in Horses

Tuniyazi,

Zhang,

Shen

2024

Preprint

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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.

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Methylated tirilazad may mitigate oligofructose-induced laminitis in horses

Tuniyazi,

Tang,

et al. 2024

Front. Microbiol.

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Laminitis is a serious health condition that can cause severe pain and lameness in horses. Due to lack of understanding of laminitis, treatments often fail to achieve the desired results. In recent years, we have begun to recognize that laminitis may involve a complex interaction between local and systemic inflammation. Dysbiosis of the gut microbiota has been linked in the development of systemic inflammation, and our previous findings suggest that the development of laminitis is closely linked to the production of harmful metabolites of the gut microbiota. In addition, it was found that localized lesions in the hoof, especially lamellar injuries, are the most direct cause of laminitis. Matrix metalloproteinases have been found to be strongly associated with the development of laminitis. Recent discovery has found that methylated tirilazad has a role in repairing laminar tissue in vitro. However, its efficacy in horses never has been studied. Therefore, we aimed to investigate the efficacy of methylated tirilazad (product name: PTP-102) in the prevention/treatment of oligofructose-induced laminitis. The results showed that oligofructose successfully induced laminitis in horses, resulting in detreated clinical signs. Blood indices (including inflammation-related indices and other related indices) were significantly increased. Observations of dissection and staining showed significant bleeding, swelling, and damage to hoof tissue. Analysis of the gut microbiota showed a significant decrease in abundance and diversity, and a significant increase in the relative abundance of specific bacteria. Following methylated tirilazad intervention, there were a significant improvement in clinical signs, blood markers and lamellar tissue damage. Additionally, methylated tirilazad positively influenced the gut microbiota structure by reducing the relative abundance of genera closely associated with the development of equine laminitis. This suggests that some of the therapeutic mechanism of methylated tirilazad may be linked to its effects on the gut microbiota. Notably, methylated tirilazad had better effect in the treatment group than the prophylactic group, indicating the post-diagnosis utility of methylated tirilazad for laminitis management.

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MMP-2 Plays an Important Role During the Early Acute Developmental Phase of Oligofructose-Induced Equine Laminitis

Cited by 5 publications

References 29 publications

High-grain diet feeding altered the composition and functions of the rumen bacterial community and caused the damage to the laminar tissues of goats

High-grain diet feeding altered the composition and functions of the rumen bacterial community and caused the damage to the laminar tissues of goats

Methylated Tirilazad (PTP-102) May Mitigate Oligofructose-Induced Laminitis in Horses

Methylated tirilazad may mitigate oligofructose-induced laminitis in horses

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