Mefepronic acid, a compound used to stimulate bile flow in horses, cattle, goats, pigs, and dogs, has not been formally evaluated for safety in sheep before now. This study is critical as veterinarians have increasingly used the drug off-label for managing conditions like fasciolosis and alongside other treatments for pregnancy toxaemia and fatty liver syndrome. A recent study published in Veterinary Medicine and Science provides the first comprehensive assessment of the drug's effects on healthy sheep's blood chemistry, indicating no significant adverse effects at the extra-label dose.
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The research team from Selcuk University’s Faculty of Veterinary Medicine conducted the study on ten male Akkaraman sheep aged eight to twelve months, weighing between 45 and 55 kilograms. The sheep were housed in identical conditions with ad libitum access to food and water, and the study protocol was approved by the university's ethics committee. Each sheep received mefepronic acid through intramuscular injection at a dose of 10 milligrams per kilogram for three consecutive days, reflecting common off-label practices. Blood samples were collected before administration and after 24, 48, and 72 hours for analysis.
The study employed sheep-specific ELISA kits and an autoanalyzer to measure various oxidative stress markers and cardiac, liver, and kidney function indicators. While no clinical symptoms such as fever or shivering developed, certain biochemical markers showed transient changes. For instance, levels of 8-hydroxy-2-deoxyguanosine increased significantly after 24 hours but reverted to baseline levels by 72 hours. Catalase activity decreased over the study period, although changes in other oxidative markers did not reach statistical significance.
Cardiac markers exhibited a similar transient pattern; creatine kinase-MB isoenzyme levels increased at 24 hours but returned to near baseline, while troponin I levels showed no significant change. The authors noted that while CK-MB can indicate myocardial injury, its elevation may not reflect genuine cardiac damage due to its nonspecific nature.
In terms of kidney function, blood urea nitrogen levels significantly decreased at 72 hours, but serum creatinine remained stable. Notably, high-density lipoprotein levels fell significantly, potentially indicating the drug's metabolic activity could aid in conditions like fatty liver syndrome by reducing circulating lipid load.
Liver function markers showed consistent results, with no significant declines during the study, aligning with the drug’s intended use in bile stimulation rather than indicating liver injury. Historical data from previous studies in other species supports these findings, suggesting mefepronic acid does not adversely affect liver health.
The authors caution that while the study's self-controlled design provided valuable insights by tracking changes within the same animals, the lack of a control group limits the ability to distinguish drug effects from natural physiological variations. They also emphasize that these findings are preliminary, especially for animals with existing health issues where the calculated shifts in oxidative stress and cardiac markers could differ.
Overall, the study offers cautious reassurance regarding the safety of mefepronic acid for healthy sheep, noting no significant adverse reactions or evidence of organ damage. However, the authors advocate for further research involving different sheep breeds and those with underlying health issues, highlighting the need for continued vigilance among practitioners using this compound in veterinary medicine.