Is it possible for a single drug to target two health concerns? This may be made possible with extensive research, but it is not particularly easy to achieve. For example, the new diabetes medication aims to address two complications that are brought by diabetes -- excess of glucose and lipids in the bloodstream. While these medications may come with health benefits, they may also come with dangerous, often toxic effects, to the human heart.
The dual PPARa/y agonists cause heart dysfunction among patients with diabetes, the clear connection as to how and why this is possible remains to be explored. In a new research published in the JCI Insight journal, researchers from the Lewis Katz School of Medicine of Temple University (LKSOM) reveals that the diabetes drug by the named PPARa/y has been found to have toxic effects on the heart, causing it to weaken. In particular, the drug weakened the function of the mitochondria, the basic function of the cell that gives it its energy,
"Our team discovered that the activation of the PPARa and the PPARy as receptors of an agonist drug, also blocked the activities, including the production of the SIRT 1," explained by Konstantinos Drosatos, assistant professor of Pharmacology and senior researcher of the study. "When we reactivated the SIRT1 using resveratrol, the toxic effect of the medicine to the heart was reduced. It still lowered the effect of glucose and lipids in the blood."
Thiazolidinediones (TZDS) which included a combination of rosiglitazone and pioglitazone bind to the PPARy receptors. Because there have been a lot of questions about the toxicity levels of these drugs when given alone, the idea to come up with the PPARa/y activator emerged. It is the use of a single drug to target two baits in theory worked and it also did when the combined glucose and lipid levels were lowered due to the PPRAa/y activation.
Dr. Drosatos and his team of scientists carried out a series of studies on diabetic mice in a laboratory. They were treated with dual PPAR a/y tesaglitazar. Despite the reduced levels of lipid and glucose in their bloodstream, the mice developed some kind of cardiac dysfunction.
Then, the researchers repeated the experiment with a combination of tesaglitazar and resveratrol, which then serves as the SIRT1 activator. The combination of two drugs as mice treatment has reduced the toxicity levels in the heart with its mitochondrial functions intact.
"Now, people have a better idea of how the toxicity levels in the heart increase with the treatment of dual PPARa/y," said Dr. Drosatos.
