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Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.
Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Enterohepatic circulation is the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Enterohepatic circulation is an especially important concept in the field of toxicology as many lipophilic xenobiotics undergo this process causing repeated liver damage.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.
NAPQI, also known as NAPBQI or N-acetyl-p-benzoquinone imine, is a toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol (acetaminophen). It is normally produced only in small amounts, and then almost immediately detoxified in the liver.
Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Their use dates back centuries and is intertwined with the discovery, understanding, and eventual recognition of their toxicity on humans and animals.
In histology, the lobules of liver, or hepatic lobules, are small divisions of the liver defined at the microscopic scale. The hepatic lobule is a building block of the liver tissue, consisting of a portal triad, hepatocytes arranged in linear cords between a capillary network, and a central vein.
Cylindrospermopsin is a cyanotoxin produced by a variety of freshwater cyanobacteria. CYN is a polycyclic uracil derivative containing guanidino and sulfate groups. It is also zwitterionic, making it highly water soluble. CYN is toxic to liver and kidney tissue and is thought to inhibit protein synthesis and to covalently modify DNA and/or RNA. It is not known whether cylindrospermopsin is a carcinogen, but it appears to have no tumour initiating activity in mice.
Nodularins are potent toxins produced by the cyanobacterium Nodularia spumigena, among others. This aquatic, photosynthetic cyanobacterium forms visible colonies that present as algal blooms in brackish water bodies throughout the world. The late summer blooms of Nodularia spumigena are among the largest cyanobacterial mass occurrences in the world. Cyanobacteria are composed of many toxic substances, most notably of microcystins and nodularins: the two are not easily differentiated. A significant homology of structure and function exists between the two, and microcystins have been studied in greater detail. Because of this, facts from microcystins are often extended to nodularins.
Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These symptoms include feeling tired, abdominal pain, or nausea. This is typically followed by absence of symptoms for a couple of days, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later.
Senecionine is a toxic pyrrolizidine alkaloid isolated from various botanical sources. It takes its name from the Senecio genus and is produced by many different plants in that genus, including Jacobaea vulgaris. It has also been isolated from several other plants, including Brachyglottis repanda, Emilia, Erechtites hieraciifolius, Petasites, Syneilesis, Crotalaria, Caltha leptosepala, and Castilleja.
Pyrrolizidine alkaloidosis is a disease caused by chronic poisoning found in humans and other animals caused by ingesting poisonous plants which contain the natural chemical compounds known as pyrrolizidine alkaloids. Pyrrolizidine alkaloidosis can result in damage to the liver, kidneys, heart, brain, smooth muscles, lungs, DNA, lesions all over the body, and could be a potential cause of cancer. Pyrrolizidine alkaloidosis is known by many other names such as "Pictou Disease" in Canada and "Winton Disease" in New Zealand. Cereal crops and forage crops can sometimes become polluted with pyrrolizidine-containing seeds, resulting in the alkaloids contaminating flour and other foods, including milk from cows feeding on these plants.
Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria. It is the most toxic of the microcystins.
Riddelliine is a chemical compound classified as a pyrrolizidine alkaloid. It was first isolated from Senecio riddellii and is also found in a variety of plants including Jacobaea vulgaris, Senecio vulgaris, and others plants in the genus Senecio.
Liver regeneration is the process by which the liver is able to replace damaged or lost liver tissue. The liver is the only visceral organ with the capacity to regenerate. The liver can regenerate after partial hepatectomy or injury due to hepatotoxic agents such as certain medications, toxins, or chemicals. Only 51% of the original liver mass is required for the organ to regenerate back to full size. The phenomenon of liver regeneration is seen in all vertebrates, from humans to fish. The liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. The process of regeneration in mammals is mainly compensatory growth or hyperplasia because while the lost mass of the liver is replaced, it does not regain its original shape. During compensatory hyperplasia, the remaining liver tissue becomes larger so that the organ can continue to function. In lower species such as fish, the liver can regain both its original size and mass.
Centrilobular necrosis (CN) is a nonspecific histopathological observation brought on by hepatotoxins like acetaminophen (paracetamol), thioacetamide, tetrachloride, cardiac hepatopathy due to acute right sided cardiac failure, and congestive hepatic injury in veno-occlusive disease, or hypoxic injury due to ischemia. Centrilobular necrosis can also be found in those with autoimmune hepatitis. Centrilobular necrosis is characterized by necrotic hepatocytes completely encircling the central vein.
Monocrotaline (MCT) is a pyrrolizidine alkaloid that is present in plants of the Crotalaria genus. These species can synthesise MCT out of amino acids and can cause liver, lung and kidney damage in various organisms. Initial stress factors are released intracellular upon binding of MCT to BMPR2 receptors and elevated MAPK phosphorylation levels are induced, which can cause cancer in Homo sapiens. MCT can be detoxified in rats via oxidation, followed by glutathione-conjugation and hydrolysis.
HepaRG cell line is a human hepatic in vitro line used in liver biology research and for assessing liver pathology, hepatotoxicity, and drug-induced injury. The HepaRG model is considered a surrogate for Primary Human Hepatocytes, which are the most pertinent model to reproduce the human liver functioning as they express 99% of the same genes.
References
- ↑ Vardanyan, R. S., and Victor J. Hruby. Synthesis of Essential Drugs. 1st ed. Amsterdam: Elsevier, 2006. Print.
- ↑ Waring, JF; Jolly, RA; Ciurlionis, R; Lum, PY; Praestgaard, JT; Morfitt, DC; Buratto, B; Roberts, C; et al. (2001). "Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles". Toxicology and Applied Pharmacology . 175 (1): 28–42. Bibcode:2001ToxAP.175...28W. doi:10.1006/taap.2001.9243. PMID 11509024.
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