Well. I'll guess. Dogs, mice, rats and humans shar
Post# of 72440
Well. I'll guess. Dogs, mice, rats and humans share many of the same metabolic enzymes in the cyp450 system. This cytochrome system is generally thought of as the livers metabolic pathway system, but really these enzymes are found in muscle tissue, in the intestines and in many part of the body - but they are most dense in the liver and so we think of them as the pathways for drug metabolism in the liver. When a drug makes a dog very sick but not a human or a mouse, researchers can then look more closely - maybe the dog doesn't have the cyp450 enzymes needed to break it down. Since dogs share so many of the same pathways as humans, then they can look further and see if some or part of the medicine or its metabolites are going thru a pathway not shared by both species. Or, is the second pass of the drug thru the system going thru a different unshared pathway? It helps them identify more closely how the liver metabolizes the drug, then how the broken down drug metabolites are metabolized, etc..
Here are a couple of paragraphs from a cyp450 research paper showing an example of species differences/commonalities in one cyp450 pathway: "CYP1A1 and CYP1A2 show strong conservation among species. CYP1A1 is expressed at very low levels in the liver of all species, whereas its expression in extrahepatic tissue,such as intestine, is variable. Similarly, CYP1A2, which is highly expressed in the liver, is more variable depending on the species. Generally, CYP1A is inducible in rodents and non-rodents, but the variable effect of some inducers, such as omeprazole, is an example of species difference in gene expression regulation. In addition, furafylline inhibits CYP1A2 activity in human, mouse, rat and dog to a different extent, whereas no inhibition was observed towards CYP1A2 in monkey."
And here is another example, from the same paper, where dogs lack specific enzyme to breakdown certain meds: "In addition, the metabolism of specific human CYP2C substrates, such as tolbutamide,warfarin and S-mephenytoin, is impaired in dog compared to human liver, illustrating an important species difference between dog and human drug metabolism [106]."
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