Advantages And Disadvantages Of Acetaminophene
Acetaminophen (APAP) is one of the most commonly used analgesic and antipyretic drugs
worldwide and easily available for use without a prescription. In 2014, over 67,000 people receive
an overdose of APAP in the US, among which around 1,200 cases ended with severe liver failure or
death [1].
Over the past two decades, considerable effort has been made to understand the mechanisms of
APAP hepatotoxicity. Although the complex molecular mechanisms remain speculative, several
theories have been proposed to explain APAP induced hepatotoxicity. During metabolism, around 5
10% APAP is biotransformed into a highly reactive metabolite, N acetyl p benzoquinone imine
(NAPQI), by several cytochrome P450 enzymes (CYPs) [2]. Normally, hepatic glutathione ... Show
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Among these cell lines, human hepatocarcinoma cells (HepG2), an easy to handle and
inexpensive cell model, is one of most frequently used cell lines in hepatotoxicity studies.
HepG2 cells, which are isolated from a hepatoblastoma, exhibit many genotypic characteristics
that are crucial for toxicity responses [11, 12]. Indeed, these cells express a low level of
CYP2E1, but the expression of other CYPs playing essential roles in APAP metabolism (such as
CYP1A1, CYP1A2, and CYP3A4) are comparable with other more metabolic competent human
hepatic models, such as HepaRG and primary human hepatocytes (PHH) [13]. CYP2E1,
exclusively located in the endoplasmic reticulum (ER) as well as mitochondria, is an effective
ROS generator in cells during catalyzing APAP metabolism to NAPQI [14, 15]. Therefore, HepG2
cells, which has a minimal level of CYP2E1 induced ROS formation, could be a useful model to
study the contribution of non CYP2E1 mediated mitochondrial specific oxidative stress in APAP
induced hepatic injury. In fact, the CYP2E1 expression and enzyme activity vary substantially in
both non compound exposed and compound exposed liver slices obtained from human donors [16,
17]. Moreover, genetic variation of CYP2E1 (CYP2E1*5, *1B and *1D), which have been
associated with
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