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2015 ; 289
(1
): 40-7
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Mechanistic review of drug-induced steatohepatitis
#MMPMID26344000
Schumacher JD
; Guo GL
Toxicol Appl Pharmacol
2015[Nov]; 289
(1
): 40-7
PMID26344000
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Drug-induced steatohepatitis is a rare form of liver injury known to be caused by
only a handful of compounds. These compounds stimulate the development of
steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of
beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation.
Other mechanisms discussed include the disruption of phospholipid metabolism in
lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial
DNA and topoisomerase, decreasing intestinal barrier function, activation of the
adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme
A. It has been found that the majority of compounds that induce steatohepatitis
have cationic amphiphilic structures; a lipophilic ring structure with a side
chain containing a cationic secondary or tertiary amine. Within the last decade,
the ability of many chemotherapeutics to cause steatohepatitis has become more
evident coining the term chemotherapy-associated steatohepatitis (CASH). The
mechanisms behind drug-induced steatohepatitis are discussed with a focus on
cationic amphiphilic drugs and chemotherapeutic agents.
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