Hepatotoxicity - experimental model

Akutne i kronične upalne bolesti jetre (hepatitisi) su česte gastrointestinalne bolesti i predstavljaju veliki zdravstveni i medicinski problem. Trenutno se liječenje hepatitisa zasniva na antivirusnoj terapiji i presađivanju jetre, ovisno o tipu i stadiju bolesti. Kod fulminantnog hepatitisa i uznapredovale ciroze jedini je način liječenja transplantacija jetre. Postojeća antivirusna terapija je nedovoljno učinkovita, skupa i s mnogo nuspojava, iz tog razloga eksperimentalni modeli hepatitisa su izuzetno važni za pronalazak novih, učinkovitijih lijekova i terapijskih sustava. Većina eksperimentalnih modela se bazira ili na kirurškim tehnikama ili na hepatotoksičnim tvarima. Korištenjem hepatotoksina na animalnim modelima stvaraju se određeni eksperimentalni modeli hepatitisa, promatra patogeneza bolesti, apliciraju se potencijalne terapeutske tvari i analizira njihova učinkovitost. Ocjenjivanje hepatotoksičnosti se vrši biokemijskim i patohistološkim metodama. Zbog reproducibilnosti hepatotoksičnog učinka u laboratorijskih životinja, model akutnog toksičnog hepatitisa uzrokovanog paracetamolom je postao najčešći pokusni model za istraživanje toksičnog djelovanja ksenobiotika na jetru. Za virusne modele razvijene do danas se pokazalo da su održivi, reproducibilni i pokazuju karakteristike slične onima kod akutnog jetrenog zatajenja u ljudi. Jedino ograničenje je da su kunići jedina osjetljiva vrsta u koje su primjenjivi. Svaki pojedinačni eksperimentalni model odražava određeni aspekt akutnog jetrenog zatajenja ali nam nedostaje model koji bi obuhvatio sve aspekte. Unatoč tim ograničenjima, eksperimentalni modeli hepatitisa će i dalje imati bitnu ulogu u budućim znanstvenim istraživanjima, pružajući nam nova otkrića o patogenezi i terapiji jetrenih bolesti.Acute and chronic inflammatory liver diseases (hepatitis), are common gastrointestinal diseases and represent a major health and medical problem. Currently the treatment of hepatitis is based on antiviral therapy and liver transplantation, depending on the type and severity of the disease. In fulminant hepatitis and advanced cirrhosis, only treatment is liver transplantation. Existing antiviral therapy is not sufficiently effective, it has many side effects, developing of experimental models of hepatitis helps to find new and more effective drugs and drug delivery systems. Most experimental models are based on surgical techniques or hepatotoxic substances. With the use of hepatotoxins in animal models, experimental models of hepatitis are being created, the pathogenesis of the disease is being observed, potential therapeutic substances are being applied and their effectiveness is being analyzed. Evaluation of hepatotoxicity is performed using biochemical and histopathological methods. Due to the reproducibility of hepatotoxic effects in laboratory animals, a model of acute toxic hepatitis caused by paracetamol has become the most common experimental model to study the toxic effects of xenobiotics on the liver. For viral models developed to date have proven to be viable, reproducible and exhibit characteristics similar to those of acute liver failure in humans. The only restriction is that rabbits are only sensitive species to which they are applicable. Each individual experimental model reflects a certain aspect of acute liver failure, but we lack a model which would encompass all aspects. Despite these limitations, experimental models of hepatitis will continue to have an important role in future scientific research, providing us with new findings about the pathogenesis and therapy of liver diseases