What causes microsomal enzyme induction?

Microsomal enzyme inducing drugs such as phenytoin, phenobarbital and carbamazepine, and also alcohol, influence serum lipid and apoprotein concentrations. The inducers increase the concentrations of hepatic microsomal enzyme and apo A-I mRNA, and also proteins and phospholipids.

What is hepatic microsomal induction?

Induction of the hepatic microsomal enzyme system The microsomal enzyme system can be activated by using an inducer drug that can bind to the receptor present in the cytoplasm or nucleus. The induction of the enzyme system can increase the metabolic rate by two to four folds.

What is hepatic enzyme induction?

Hepatic enzyme induction is generally an adaptive response associated with increases in liver weight, induction of gene expression, and morphological changes in hepatocytes.

What is the significance of the hepatic microsomal enzyme induction?

Hepatic microsomal enzymes play an important role in thyroid hormone homeostasis. Glucuronidation of thyroxine is the rate limiting step in the biliary excretion of thyroxine in the rat; the monodeiodinases are important in the conversion of T4 to T3 and reverse T3 and subsequent deiodinations.

What are the consequences of the induction of microsomal enzymes?

Inducers of microsomal enzymes stimulate the metabolism or synthesis of several normal body substrates such as steroid hormones, pyridine nucleotides, cytochromes, and bilirubin. Evidence has accumulated that steroids are normal body substrates of drug-metabolizing enzymes in liver microsomes.

What enzyme does Phenobarbital induce?

Phenobarbital is a potent enzyme inducer known for hepatotoxicity and for inducing its own metabolism. Rifampin induces the metabolism of azole antifungals; concurrent administration with itraconazole results in subtherapeutic itraconazole concentrations.

What are hepatic microsomes?

Liver microsomes are subcellular fractions which contain membrane bound drug metabolising enzymes. Microsomes can be used to determine the in vitro intrinsic clearance of a compound. The use of species-specific microsomes can be used to enable an understanding of interspecies differences in drug metabolism.

What is microsomal enzyme inhibition?

The microsomal enzymes that metabolize drugs are localized in the smooth endoplasmic reticulum. Several drugs, including fluconazole, spironolactone, and metronidazole, can inhibit cytochrome P450 enzyme activity. This inhibition reduces the metabolism of potential substrates and secondarily delays their elimination.

What is the enzyme found in liver?

ALT is an enzyme that helps break down proteins and is found mainly in your liver. High levels in your blood could mean you have liver damage. Alkaline phosphatase (ALP) test. ALP is an enzyme in your liver, bile ducts, and bone.

What are inhibitors of hepatic enzyme?

Among the potent enzyme inhibitors commonly used in clinical practice are some azole antifungals, protease inhibitors such as ritonavir, macrolide antibiotics such as erythromycin and selective serotonin re-uptake inhibitors such as fluoxetine.

What happens when there is enzyme induction and enzyme inhibition?

Enzyme induction and inhibition. Frequent administration of certain drugs leads to increased synthesis (transcription or translation), or induction, of P450 enzymes. Enzyme induction increases metabolism of all drugs that are metabolized by that particular P450 isoenzyme.

What does an enzyme inducer do?

An enzyme inducer is a type of drug that increases the metabolic activity of an enzyme either by binding to the enzyme and activating it, or by increasing the expression of the gene coding for the enzyme. It is the opposite of an enzyme repressor.

How is Hepatic enlargement related to enzyme induction?

Liver Enlargement – Hepatic Enzyme Induction: Histopathology. Liver Enlargement – Hepatic Enzyme Induction: Histopathology. Hepatic enzyme induction is generally an adaptive response associated with increases in liver weight, induction of gene expression, and morphological changes in hepatocytes.

What causes hepatic transaminases to increase in dogs?

Hepatic transaminases increase with muscle injury as well as vigorous physical activity in dogs. Persistence of transaminases in plasma contributes to their sustained high activities in certain disorders.

Why does Alt increase in dogs with hepatic disease?

Enzyme fluctuations contrast with profiles associated with single injurious events. In dogs with hepatitis, serum ALT activity declines as injury resolves, but serum ALP activity may increase as a result of regenerative responses (progenitor cell proliferation, ductal or oval cell response).

What is low grade hepatocellular degeneration in dogs?

Low-grade hepatocellular degeneration, observed in some dogs with congenital portosystemic shunts, reflects delayed enzyme clearance and low-grade hepatocyte dropout; most of these dogs have small lipogranulomas reflecting single hepatocyte dropout/necrosis in the absence of an inflammatory response.