Toxic Responses of the Liver Flashcards
1
Q
The ________ is the main organ where exogenous chemicals are metabolized and eventually excreted.
A
liver
2
Q
T/F: The liver, with its multiple cell types and numerous functions, can respond in many different ways to acute and chronic insults.
A
True
3
Q
The liver’s strategic location between ______________ and the rest of the body facilitates its maintenance of metabolic ______________ in the body.
A
intestinal tract; homeostasis
4
Q
The liver extracts ingested nutrients, vitamins, metals, drugs, environmental toxicants, and waste products of bacteria from the blood for ____________, ___________, and/or excretion into ________.
A
catabolism; storage; bile
5
Q
Formation of bile is essential for the uptake of ________ nutrients from the small intestine, protection of the small intestine from ___________ insults, and __________ of endogenous and xenobiotic compounds.
A
lipid; oxidative; excretion
6
Q
_______________ is either a decrease in the volume of bile formed or an impaired secretion of specific solutes into bile
A
Cholestasis
7
Q
Hepatocytes have a rich supply of _______________ and _______________ and thereby enhance their removal from the body.
A
phase I enzymes; phase II enzymes
8
Q
T/F: phase II reactions determines whether a reactive metabolite will initiate liver cell injury or be safely detoxified.
A
False. The balance between phase I and phase II reactions determines whether a reactive metabolite will initiate liver cell injury or be safely detoxified.
9
Q
These enzymes includes processes such as redox, and converting xenobiotics to electrophilic metabolites
A
phase I enzymes
10
Q
These enzymes include conjugation, and glucuronidation that adds a polar group to a molecule, enhancing their removal from the body
A
phase II enzymes
11
Q
It is a yellow pigment that also passes through the liver and excreted out from the body. Its high levels indicate liver or bile duct problems
A
Bilirubin
12
Q
Cholestasis is a result of elevated serum levels of ____________ and ____________, which slows down the normal flow of the bile from the ______________. It causes itching, and jaundice
A
bile salts; bilirubin; gallbladder
13
Q
T/F: The liver is the third organ, after the stomach, to encounter ingested nutrients, vitamins, metals, drugs, and environmental toxicants and waste products of bacteria that enter portal blood.
A
False. Liver is the first organ
14
Q
T/F: The venous blood coming from the stomach and intestines also flows to the portal vein and to the liver, and eventually enter the systemic circulation
A
True
15
Q
The loss of function of the liver also occurs if the toxicants kill a considerable amount of cells and when chronic insults lead to a replacement of cell mass by a non-functional ______________.
A
scar tissue
16
Q
Bile contains bile acids, ______________, _____________, ______________, bilirubin, and other organic anions, proteins, ________, ions, and xenobiotics.
A
glutathione; phospholipids; cholesterol; metals
17
Q
Hepatocytes begin the process by transporting bile acids, glutathione, and other solutes, including xenobiotics and their metabolites, into the ________________.
A
canalicular lumen
18
Q
The canaliculi are separated from the ________________ between hepatocytes by ______________, which form a barrier permeable only to water, electrolytes, and to some degree to small ____________.
A
intercellular space; tight junctions; organic cations
19
Q
This is the space formed by the specialized regions in the plasma membrane between the adjacent hepatocytes
A
canalicular lumen
20
Q
This structure forms channels between the hepatocytes that connect to a series of larger channels or ducts within the liver
A
canaliculi
21
Q
T/F: The major driving force of bile formation is the active transport of bile salts and other osmolytes into the major bile ducts.
A
False. The major driving force of bile formation is the active transport of bile salts and other osmolytes into the canalicular lumen.
22
Q
Sodium-independent uptake of conjugated and unconjugated bile acids is performed by members of the ______________________________.
A
organic anion transporting polypeptides (OATPs)
23
Q
T/F: Most conjugated bile acids like taurine and glycine conjugates are transported into hepatocytes by sodium-dependent transporters
A
True
24
Q
T/F: OATPs also transport numerous drugs and hepatotoxicants.
A
True
25
Lipophilic cationic drugs, estrogens, and lipids are exported by the canalicular ____________________________, one of which is exclusive for _____________.
multiple drug resistance (MDR) P-glycoprotein; phospholipids
26
Conjugates of glutathione, glucuronide, and sulfate are exported by ________________________________.
multidrug resistance–associated protein 2 (MRP2)
27
Name every efflux transporter
BSEP, bile salt export pump; MDR, multidrug resistance protein; MRP, multidrug resistance-associated protein; ABCG5/8, heterodimeric ATP binding cassette transporter G5/G8; BCRP, breast cancer resistance protein; Ostα/Ostβ, heterodimeric organic solute transporter alpha, and beta.
28
Name every uptake transporter
ASBT, apical sodium dependent bile salt transporter; NTCP, sodium taurocholate transporting polypeptide; OATP, organic anion transporting polypeptide; OCT, organic cation transporter; OAT, organic anion transporter.
29
Biliary excretion is important in the homeostasis of metals, notably copper, _____________, ____________, _______________, gold, silver, and _______________.
manganese; cadmium; selenium; arsenic
30
Inability to export Cu into bile is a central problem in ___________________, a rare genetic disorder characterized by accumulation of Cu in the liver and then in other tissues.
Wilson’s disease
31
These are biliary epithelial cells that lines the bile duct tubules and serves to transport bile from the liver to the small intestines
cholangiocytes
32
T/F: Hepatocytes executes most metabolic functions including bile secretion
True
33
___________ modify bile by absorption and secretion of solutes
Bile ducts
34
T/F: Secretion into biliary ducts is always a prelude to toxicant clearance by excretion in feces or urine.
False. Secretion into biliary ducts is usually, but not always, a prelude to toxicant clearance by excretion in feces or urine.
35
Exceptions occur when compounds are repeatedly delivered into the intestinal lumen via bile, efficiently absorbed from the intestinal lumen, and then redirected to the liver via portal blood, a process known as __________________.
enterohepatic cycling
36
T/F: Toxicant-related impairments of bile formation are more likely to have detrimental consequences in populations with other conditions where biliary secretion is marginal.
True
37
This type of hepatobiliary injury is caused by representatives toxins like amiodarone, CCl4, ethanol, fialuridine, tamoxifen, and valproic acid
Fatty liver
38
This type of hepatobiliary injury is caused by representatives toxins like acetaminophen, allyl alcohol, Cu, dimethylformaldehyde, and ethanol
Hepatocyte death
39
This type of hepatobiliary injury is caused by representatives toxins like diclofenac, ethanol, halothane, and tienilic acid
Immune-mediated response
40
This type of hepatobiliary injury is caused by representatives toxins like chlorpromazine, cyclosporin A, 1,1-dichloroethane, estrogens, Mn, and phalloidin
Canalicular cholestasis
41
This type of hepatobiliary injury is caused by representatives toxins like alpha-naphthylisothiocyanate, amoxicillin, methylene dianiline, and sporidesmin
Bile duct damage
42
This type of hepatobiliary injury is caused by representatives toxins like anabolic steroids, cyclophosphamide, microcystin, and pyrrolizidine alkaloids
Sinusoidal disorders
43
This type of hepatobiliary injury is caused by representatives toxins like CCl4, ethanol, thioacetamide, vitamin A, and vinyl chloride
Fibrosis and cirrhosis
44
This type of hepatobiliary injury is caused by representatives toxins like aflatoxin, androgens, arsenic, thorium dioxide, and vinyl chloride
Tumors
45
What are the hepatobiliary injuries caused by ethanol?
Fatty liver, hepatocyte death, immune-mediated response, fibrosis and cirrhosis
46
What are the hepatobiliary injuries caused by CCl4?
Fatty liver, fibrosis and cirrhosis
47
What are the hepatobiliary injuries caused by vinyl chloride?
fibrosis and cirrhosis, and tumors
48
____________ is characterized by cell swelling, leakage, nuclear disintegration (karyolysis), and an influx of inflammatory cells.
Necrosis
49
T/F: Apoptosis is characterized by cell shrinkage, nuclear disintegration, formation of apoptotic bodies, and a lack of inflammation.
False. Apoptosis is characterized by cell shrinkage, nuclear FRAGMENTATION, formation of apoptotic bodies, and a lack of inflammation.
50
T/F: Apoptosis can be detected biochemically by assaying plasma (or serum) for liver cytosol-derived enzymes - AST or ALT or GGT
False. Necrosis can be detected biochemically by assaying plasma (or serum) for liver cytosol-derived enzymes - AST or ALT or GGT
51
T/F: Apoptosis is always a single-cell event, for the purpose of removing cells no longer needed during development or elimination of aging cells
True
52
It is the death of hepatocytes in certain functional regions.
Zonal necrosis
53
It is characterized by the randomly distributed death of single hepatocytes or small clusters of hepatocytes.
Focal cell death
54
It is a massive death of hepatocytes with only a few or no remaining survivors.
Panacinar necrosis
55
Mechanisms of toxicant-induced injury to liver cells include ________________, binding to cell _________________, _______________________, disruption of the cytoskeleton, and massive _______________.
lipid peroxidation; macromolecules; mitochondrial damage; calcium influx
56
The mechanisms of toxicant-induced injury leads to mitochondrial membrane permeability transition pore opens, causing __________ of the membrane potential, depletion of cellular ________, and necrotic cell death.
collapse; ATP
57
T/F: The loss of ATP inhibits the ion pumps in the plasma membrane results in the loss of cellular ion homeostasis and causes the characteristic swelling of necrosis, which would lead to cellular edema and destruction of the cell membrane
True
58
In canalicular cholestasis, when biliary excretion of the yellowish bilirubin pigment is impaired, this pigment accumulates in the skin and eyes, producing ____________, and spills into urine, which becomes ________________________.
jaundice; bright yellow or dark brown
59
T/F: Toxicant-induced cholestasis can be transient or chronic; when substantial, it is associated with cell swelling, cell death, and inflammation.
True
60
In canalicular cholestasis, ___________________ is vulnerable to toxicant effects on the functional integrity of sinusoidal transporters, canalicular exporters, cytoskeleton-dependent processes for transcytosis, and the contractile closure of the canalicular lumen.
bile formation
61
Changes that weaken the junctions that form the structural barrier between the blood and the canalicular lumen allow solutes to ____________ of the canalicular lumen.
leak out
62
One hepatotoxicant that causes tight junction leakage is ______________________.
α-naphthylisothiocyanate
63
What are the six potential mechanisms for cholestasis?
Impaired intake, diminished transcytosis, impaired secretion, diminished contractility of canaliculus, leaky paracellular junctions, and concentration of reactive species
64
What potential mechanism of cholestasis can result from inhibition of a transporter or retraction of a transporter away from the canalicular membrane
Impaired secretion
65
T/F: Compounds that produce cholestasis do not necessarily act by a single mechanism or at just one site.
True
66
________________ impairs bile acid uptake and canalicular contractility.
chlorpromazine
67
__________________ is a well-known cause of reversible canalicular cholestasis.
estrogens
68
__________________________ decrease bile salt uptake by effects at the sinusoidal membrane, including a decrease in the Na+,K+ATPase necessary for Na-dependent transport of bile salts across the plasma membrane and changes in the lipid component of this membrane.
Estrogens and progestins
69
T/F: Most chemicals that cause canalicular cholestasis are excreted in bile where proteins and lipids in the canalicular region encounter a high concentration of these chemicals.
True
70
Observations consistent with the concentration mechanism in the bile have been reported for ________, reactive thioether glutathione conjugates of _______________, and ____________.
Mn; 1,1-dichloroethylene; sporidesmin
71
T/F: OATPs can contribute to the liver injury potential of toxicants.
True
72
T/F: The hepatotoxicity of phalloidin, microcystin, and amanitin is facilitated by the efflux through OATPs.
False. The hepatotoxicity of phalloidin, microcystin, and amanitin is facilitated by the UPTAKE through OATPs.
73
____________, ___________, and _____________, which are known to directly inhibit the bile salt export pump (BSEP).
Rifampicin; bosentan; troglitazone;
74
_____________________ inhibit BSEP from the canalicular side after excretion by MRP2.
Estrogens and progestins
75
A substantial inhibition of _________________ can lead to the accumulation of these compounds in hepatocytes and may directly cause cell injury.
bile salt excretion
76
Bile acids are substrates for the __________________________________, downregulate NTCP and limit bile acid uptake.
nuclear farnesoid X receptor (FXR)
77
_____________ causes increased expression of transporters on the canalicular and basolateral membranes, which all work to limit the amount of bile acid accumulation.
FXR Activation
78
Damage to the intrahepatic bile ducts (which carry bile from the liver to the GI tract) is called ________________________________.
cholangiodestructive cholestasis
79
A useful biochemical index of bile duct damage is a sharp elevation in ___________________________ activity.
serum alkaline phosphatase
80
Bile duct injury may cause sloughing of the epithelial cells into the lumen, cell edema, and inflammation which may contribute to _____________
obstruction
81
Initial lesions following a single dose of cholangiodestructive agents include
1. swollen _________________,
2. debris of damaged cells within _____________ of the biliary tract, and;
3. inflammatory cell infiltration of _____________
biliary epithelium
lumens
portal tracts
82
A rare response is the loss of bile ducts, a condition known as ______________________.
vanishing bile duct syndrome
83
Vanishing bile duct syndrome has been reported in patients receiving _____________, anabolic steroids, contraceptive steroids, or __________________.
antibiotics; carbamazepine
84
It is a specialized capillary with numerous fenestrae for high permeability.
sinusoid
85
Functional integrity of the sinusoid can be compromised by dilation or blockade of its lumen or by progressive destruction of its _____________________.
endothelial cell wall
86
______________ will occur when red blood cells become caught in the sinusoids.
Blockade
87
A consequence of extensive sinusoidal blockade is that the liver becomes engorged with blood cells, and the rest of the body goes into ____________.
shock
88
It is a rare liver vascular injury disease characterized by damage to small, hepatic vessels affecting small sinusoidal epithelium that would result in complications such as intrahepatic congestion, liver damage, and portal hypertension
Sinusoidal Obstruction Syndrome (SOS)
89
Disruptions of the sinusoid are considered the early structural features of the vascular disorder known as ____________________.
venoocclusive disease
90
Venoocclusive disease occurs after exposure to ____________________
pyrrolizidine alkaloids
91
This is a condition where some veins in the liver are blocked, and causes a decrease of blood flow inside the liver and may lead to liver damage.
Venoocclusive disease
92
Venoocclusive disease is a clinical syndrome characterized by _____________, ____________, _____________, and jaundice due to sinusoidal congestion.
hepatomegaly; ascites; weight gain
93
The most frequent cause of venoocclusive disease is _____________________________, and it is also seen after solid organ transplantation
hematopoietic stem cell transplantation
94
_____________, and _____________ disrupt the integrity of the hepatocyte cytoskeleton by affecting proteins that are vital to its dynamic nature, preventing the disassembly of actin filaments.
Phalloidin and microcystin
95
_____________ uptake into hepatocytes leads to an accentuated actin web of cytoskeleton, and the canalicular lumen dilates.
Phalloidin
96
T/F: Phalloidin came from fungal sources, while microcystin is from blue-green algae
True
97
_______________ uptake into hepatocytes leads to hyperphosphorylation of cytoskeletal proteins.
Microcystin
98
_____________________ of cytoskeletal structural and motor proteins are critical to the dynamic integrity of the cytoskeleton.
Reversible phosphorylations
99
_______________________________ produced by large amounts of microcystin leads to marked deformation of hepatocytes
Extensive hyperphosphorylation
100
Lower doses of microcystin interfere with vesicle transport by hyperphosphorylating the transport protein, _____________.
dynein
101
_____________, or steatosis, is defined as an appreciable increase in the hepatic lipid content, which is <5 wt% in the normal human liver.
Fatty liver
102
__________________ due to central obesity and sedentary lifestyle.
Insulin resistance
103
T/F: Insulin resistance is the most common cause of hepatic steatosis
True
104
Acute exposure to hepatotoxicants like ___________________ and some drugs can induce steatosis.
carbon tetrachloride
105
____________ is by far the most relevant drug or chemical leading to steatosis in humans and in experimental animals.
Ethanol
106
T/F: Drug-induced steatosis is reversible and does not lead to the death of hepatocytes.
True
107
The metabolic inhibitors _________,__________, and ___________ cause fat accumulation without causing cell death.
ethionine, puromycin, and cycloheximide
108
Although steatosis alone may be benign, it can develop into __________________, which can be alcoholic or non-alcoholic, which is associated with significant liver injury.
steatohepatitis
109
Livers with steatosis can be more susceptible to additional insults such as hepatotoxicants or _________________
hepatic ischemia
110
The previously preferred hypothesis of nonalcoholic steatohepatitis (NASH) considered ______________________ in hepatocytes as the initial pathological event causing steatosis, with any additional stress (e.g., oxidant stress or lipid peroxidation) causing progression to steatohepatitis.
triglyceride accumulation
111
T/F: Triglyceride accumulation with any additional stress has recently been overturned and a new hypothesis postulates that nonalcoholic fatty liver disease (NAFLD) is mainly caused by lipotoxicity of nontriglyceride fatty metabolites.
True
112
________________ is the accumulation of extensive amounts of collagen fibers in response to direct injury or to inflammation.
hepatic fibrosis
113
Hepatic fibrosis, with repeated chemical insults, destroyed hepatic cells are replaced by ______________.
fibrotic scars
114
The primary cause of hepatic fibrosis/cirrhosis in humans worldwide is ______________.
viral hepatitis
115
Fibrosis can be induced by chronic exposure to drugs and chemicals, especially ____________ and ___________
ethanol and heavy metals.
116
T/F: Cirrhosis is reversible, but it has a poor prognosis for survival, and is usually the result of repeated exposure to chemical toxicants.
False. Not reversible
117
The rare, highly malignant angiosarcomas are derived from _____________________.
sinusoidal lining cells
118
Hepatocellular cancer has been linked to abuse of ____________, _____________, and a high prevalence of ____________-contaminated diets.
androgens; alcohol; aflatoxin
119
_______________, or thorium dioxide, accumulates in Kupffer cells and emits radioactivity throughout its very extended half-life, thus increasing the risk of developing __________________ about 14-fold and over 100-fold for liver cancers.
Thorotrast; gallbladder cancer
120
These are phagocytic cells that forms the lining of the sinusoids of the liver and is involved in the breakdown of red blood cells
Kupffer cells
121
T/F: The membrane-rich liver concentrates hydrophilic compounds.
False. The membrane-rich liver concentrates lipophilic compounds.
122
T/F: Other toxicants are rapidly extracted from blood because they are substrates for sinusoidal transporters.
True
123
______________________ initially affects the sinusoidal stellate cells, which actively extract and store this vitamin.
Vitamin A hepatotoxicity
124
______________________ becomes manifest when cells exceed their capacity to complex cadmium with the metal binding protein __________________
Cadmium hepatotoxicity; metallothionein
125
T/F: Alcoholics are vulnerable to the hepatotoxic effects of acetaminophen at dosages within the high therapeutic range.
True
126
The hepatotoxic effects of acetaminophen has widely been attributed to accelerated bioactivation of acetaminophen to the electrophilic ___________________________________ intermediate by ethanol induction of CYP2E1
N-acetyl-p-benzoquinone imine (NAPQI)
127
T/F: Inhibitors of CYP3A, including many drugs and dietary chemicals, potentially influence acetaminophen toxicity.
False. Inducers of CYP3A
128
T/F: In acetaminophen metabolism, large doses are enhanced by fasting and other conditions that deplete glutathione
True
129
Antidote for acetaminophen toxicity
N-acetylcysteine (NAC)
130
T/F: Morbidity and mortality associated with the consumption of alcohol is mainly caused by the toxic effects of ethanol on the liver.
True
131
T/F: The targeted toxicity is due to the fact that <60% of a dose of ethanol is metabolized in the liver.
False. >90%
132
T/F: The bioactivation of ethanol by alcohol dehydrogenase to acetaldehyde is the primary pathway of ethanol metabolism
True
133
Both enzymes exhibit genetic polymorphisms that result in higher concentrations of acetaldehyde—a “________(fast/slow)” activity isozyme of alcohol dehydrogenase [ALD2*2] and a physiologically very “_________(fast/slow)” mitochondrial isozyme of aldehyde dehydrogenase [ALDH2*2].
Both enzymes exhibit genetic polymorphisms that result in higher concentrations of acetaldehyde—a “FAST” activity isozyme of alcohol dehydrogenase [ALD2*2] and a physiologically very “SLOW” mitochondrial isozyme of aldehyde dehydrogenase [ALDH2*2].
134
T/F: Approximately 50% of the Asian population have slow aldehyde dehydrogenase, which explains why their alcohol consumption with this slow polymorphism leads to uncomfortable symptoms of flushing, and nausea due to high levels of acetaldehyde in the system
True
135
The second major pathway involves the ____________________________, which __________ethanol to acetaldehyde.
alcohol-inducible enzyme CYP2E1; oxidizes
136
The third pathway involves __________________. In this reaction, ethanol functions as an electron donor for the reduction of hydrogen peroxide to _________.
catalase in peroxisomes; water
137
T/F: The capacity of alcohol-inducible enzyme CYP2E1 pathway is limited due to the low levels of hydrogen peroxide, where it is estimated that only less than 2% of the ethanol dose is metabolized through this pathway.
False. The catalase in peroxisomes pathway has the limited capacity.
138
What ethanol metabolism pathway is located predominantly to hepatocytes of the centrilobular regions and requires oxygen and NADPH?
alcohol-inducible enzyme CYP2E1
139
T/F: Due to the nature of alcohol inducible enzyme CYP2E1, its reaction is the most relevant for high doses of ethanol and chronic alcoholism
True
140
_________________ is used as a model hepatotoxicant due to its preferential periportal (zone 1) hepatotoxicity.
Allyl alcohol
141
Allyl alcohol is metabolized by alcohol dehydrogenase to _________, a highly reactive aldehyde, which is then further oxidized by aldehyde dehydrogenase to ________________.
acrolein; acrylic acid
142
T/F: Acrolein formation is a critical event in liver injury.
True
143
T/F: Age and gender differences in allyl alcohol hepatotoxicity can be explained by variations in the balance between alcohol dehydrogenase and aldehyde dehydrogenase expression.
True
144
The preferential occurrence of allyl alcohol injury in zone 1 hepatocytes is caused by the predominant uptake of allyl alcohol in the _________________ and the __________ dependence of the toxicity.
periportal region; oxygen
145
______________________ is caused by reductive stress where the excessive NADH formation leads to the mobilization of redox-active iron from storage proteins.
Lipid peroxidation
146
T/F: Lipid peroxidation cannot become a relevant mechanism of cell injury because a compromised antioxidant status is not a contributing factor in its mechanism.
False. Lipid peroxidation can become a relevant mechanism of cell injury under conditions of compromised antioxidant status.
147
_______________–dependent conversion of CCl4 to CCl3 and then to CCl3OO is the classic example of xenobiotic bioactivation to a free radical that initiates lipid peroxidation.
Cytochrome P450
148
T/F: CCl3 involves CYP2E1.
True
149
_________-induced lipid peroxidation increases the permeability of the plasma membrane to Ca2+, leading to severe disturbances of calcium homeostasis and _____________.
CCl4; necrotic cell death
150
Recent research indicates that CCl4 also induces significant ________________________, which is dependent on lipid peroxidation events and on ____________ activity.
mitochondrial damage; CYP2E1
151
The liver has a high capacity to restore lost tissue and function by ________________.
regeneration
152
T/F: Loss of hepatocytes due to hepatectomy or cell injury triggers the proliferation of all immature liver cells.
False. Mature liver cells
153
Tissue repair is _________________ up to a threshold, after which the injury is too severe and cell proliferation is inhibited.
dose–responsive
154
The main reason for an inflammatory response is to remove ________ and __________ cells.
dead; damaged
155
T/F: In an inflammatory response, under certain circumstances, these inflammatory cells can aggravate the existing injury by the release of directly cytotoxic mediators or by the formation of pro and anti-inflammatory mediators.
True
156
What are the chemicals that induce immune-mediated injury mechanisms in the liver
halothane, tienilic acid, and dihydralazine
157
A delay in the onset of the injury or the requirement for repeated exposure to the drug and the formation of antibodies against drug-modified hepatic proteins are characteristic features of _______________, but the mechanisms are not well understood.
immune reactions
158
T/F: Two proposed mechanisms of canalicular cholestatic liver injury are the hapten hypothesis and the danger hypothesis
False. Two proposed mechanisms of immune-mediated liver injury are the hapten hypothesis and the danger hypothesis
159
________________ promotes helper T-cell activation leading to T-cell responses to the antigen.
Hapten formation
160
The danger hypothesis postulates that damaged cells release _____________, which induce the upregulation of a peripheral protein B7 on activated _____________________, which, when paired with ________ on T cells, generates a costimulatory signal.
danger signals; antigen-presenting cells (APCs); CD28
161
T/F: In immune-mediated idiosyncratic hepatotoxicity, the absence of this costimulatory signal, the antigens derived from drug-modified proteins inhibits immune tolerance.
False. In the absence of this costimulatory signal, the antigens derived from drug-modified proteins INDUCE immune tolerance.
162
__________________ drugs for the therapy of hepatitis B and AIDS infections cause mitochondrial DNA damage directly, when incorporation of the analog base leads to ___________ or early termination of polypeptides.
Nucleoside analog; miscoding
163
The severe hepatic mitochondrial injury produced by the nucleoside analog ____________ is attributed to its higher affinity for the polymerase responsible for mitochondrial DNA synthesis than for the polymerases responsible for nuclear DNA synthesis.
fialuridine
164
T/F: Mitochondrial DNA is also more vulnerable to miscoding (mutation) due to its limited capacity for repair.
True
165
T/F: Alcohol abuse causes mitochondrial injury by miscoding or mutation
False. Alcohol abuse causes mitochondrial injury by shifting the bioactivation/detoxification balance for ethanol
166
T/F: Idiosyncratic drug hepatotoxicity is a rare but potentially serious adverse event, which is dose-dependent.
False. Idiosyncratic drug hepatotoxicity is a rare but potentially serious adverse event, which is not clearly dose-dependent.
167
T/F: Idiosyncratic toxicity is a leading cause of the failure of drugs in clinical testing, and it is the most frequent reason for posting warnings, restricting use, or even withdrawing the drug from the market.
True
168
T/F: It is likely that gene defects is the only requirement to be present in an individual to trigger the severe liver injury.
False. It is likely that a combination of gene defects and adverse events need to be present simultaneously in an individual to trigger the severe liver injury.
169
A detailed _________________ of patients with idiosyncratic responses to drug exposure may give additional insight.
genomic analysis
