Thiopurine methyltransferase in red blood cells of dogs, cats, and horses.

The research investigated the presence and levels of thiopurine methyltransferase (TPMT), an enzyme crucial to the metabolism of a drug called azathioprine, in the red blood cells of healthy dogs, cats, and horses. The study found that TPMT could be detected in all three species, with significant variations in levels.

Research Methodology

• The researchers aimed to find out if TPMT, an enzyme that is critical in the metabolism of azathioprine in human beings, could be detected in the red blood cell lysates (RBCL) of dogs, cats, and horses.
• To achieve this, they collected blood samples from 20 healthy animals from each species and measured the TPMT activity in these animals’ RBCL.
• They did so by using a method known as a radioenzymatic end point, which facilitated the metabolism of a substance called 6-mercaptopurine to 6-methylmercaptopurine (6-MMP).
• One unit of TPMT activity was defined as the formation of 1 nmol of 6-MMP per milliliter of packed red blood cells per hour of incubation at 37 degrees Celsius.

Research Findings

• The researchers were successful in detecting TPMT activity in the RBCL of all the three species. The mean TPMT activity was found to be 17.9 U/mL in dogs, 2.76 U/mL in cats, and 2.185 U/mL in horses.
• Notably, the differences in the TPMT values between the species were statistically significant. The TPMT activity of dogs was much higher than that of the other species, and cats had higher activity than horses.

Implications and Conclusions

• The findings of the study show that TPMT values are measurable in dogs, cats, and horses, and that these values differ significantly among the species.
• This could explain why cats have a lower tolerance for azathioprine compared to dogs. This is because TPMT is an essential enzyme involved in the metabolism of azathioprine, and the levels of TPMT may influence the metabolic response to the drug.
• However, it has not yet been determined if these RBC TPMT values in these animals correlate with the enzyme’s activity in the liver, where the majority of azathioprine metabolism happens.