Ischemic liver damage

A causal association has been shown between the hepatotoxicity of ciclosporin and cold ischemic liver damage that can occur during preservation before liver transplantation (85). This presents a problem when ciclosporin is used after liver transplantation. In more than 1000 patients there was an incidence of mild reversible hepatotoxicity of 40% in patients taking 5-fluorouracil and levamisole as adjuvants for more than 1 year the incidence of mild hepatotoxicity in those taking levamisole alone and amongst those receiving no treatment at all was the same, a little over 16% (86). 

Progression of liver disease during parenteral nutrition in two infants with intestinal failure was rapidly exacerbated by ischemic liver damage [67 ]. 

Bcl-2 B cell lymphoma protein 2 (Bcl-2) is a family of proteins that regulate apoptosis (programmed cell death). Apoptosis is a necessary process whereby aged or damaged cells are replaced by new cells. Dysfunction of the apoptosis process results in disease inhibition of apoptosis results in cancer, autoimmune disorder, and viral infection, whereas increased apoptosis gives rise to neurodegenerative disorders, myelodysplastic syndromes, ischemic injury, and toxin-induced liver disease. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

Chronic exposure has been shown to damage the liver, kidney, and other major systems and has been correlated with an increased risk of ischemic heart disease. Literature reports of the human LDlo by the oral route range from 0.14 to 14gkg. Phenol is a known mutagen however, conclusive carcinogenic data are not available. In laboratory experiments, it does show teratogenic and reproductive effects. 

Liposomal ATP protected human endothelial cells from energy failure in a cell culture model of sepsis (21). ATP-L increased the number of ischemic episodes tolerated before electrical silence and brain death in the rat (22,23). In a hypovolemic shock-reperfusion model in rats, the administration of ATP-L increased hepatic blood flow during shock and reperfusion of the liver (24). The addition of the ATP-L during cold storage preservation of rat liver improved its energy state and metabolism (25,26). Co-incubation of ATP-L with sperm cells improved their motility (27). Finally, biodistribution studies demonstrated significant accumulation of ATP-L in ischemia-damaged canine myocardium (28). 

It is related to abnormal endothelial reactivity that leads to intravascular deposition of fibrin with subsequent end-organ damage. Most maternal deaths are due to central nervous system complications, but the liver may also be the target of injury. The injury to the liver is ischemic. Modest elevations in ALT and AST occur, typically 4 to 10 times the upper reference limit. Hepatic complications, including hemorrhage, infarction, and fulminant hepatic failure, may occur and necessitate early delivery... 

A metal ion not infrequently implicated in superoxide-associated damage to cells is Fe ". It is known that Fe can form complexes with superoxide, thereby leading to the formation of peroxide or even possibly OH-radicals, which are highly damaging. It is also feasible that damage can result from the interaction of superoxide with other metal ions. Isolated mitochondria swell rapidly when incubated in the presence of Ca. Such cells can be protected for long periods by 10% dimethylsulfoxide, an agent which readily destroys peroxide. Suspensions of liver cells tolerate ischemic... 

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