Page 330 - Industrial Ventilation Design Guidebook

286 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

be observed from outside the cell. Ultimately, the cellular particles are phago-
cytized by the surrounding cells without any inflammatory process. This is
one of the characteristic morphological differences between necrotic and apo-
ptotic cell death: whereas inflammation is typical for necrosis, lack of inflam-
89 91
mation is the hallmark of apoptosis. ' See Table 5.10 for features of
apoptosis. Table 5.11 lists events important for necrosis.
Exposure to chemical compounds such as some heavy metals (e.g., lead)
may activate apoptosis in a non-physiological way, leading to organ injury

2
TABLE 5.11 Agents Causing Sustained Elevation of Cytosolic Ca * and/or
Impaired Synthesis of ATP
2+
A. Agents inducing Ca influx into the cytoplasm
I. Via ligand-gated channels in neurons:
1. Glutamate receptor agonists ("excitotoxins"): glutamate, kainate,
domoate
2. "Capsaicin receptor" agonists: capsaicin, resiniferatoxin
II. Via voltage-gated channels: maitotoxin (?) OH*
III. Via "newly formed pores": maitotoxin, amphotericin B, chlordecone,
methylmercury alkyltins
IV. Across disrupted cell membrane:
1. Detergents: exogenous detergents, lysophospholipids, free fatty
acids
2. Hydrolytic enzymes: phospholipases in snake venoms, endogenous
phospholipase A 2
3. Lipid peroxidants: carbon tetrachloride
4. Cytoskeletal toxins (by inducing membrane blebbing):
cytochalasins, phalloidin
V, From mitochondria: see D
2+
2+
B. Agents inhibiting Ca export from the cytoplasm (inhibitors of Ca -ATPase in
cell membrane and/or endoplasmic reticulum)
I. Covalent binders: acetaminophen, bromobenzene, CC1 4,
chloroform, DCE
II. Thiol oxidants: cystamine (mixed disulfide formation), diamide, f-BHP,
menadione, diquat
III. Others: vanadate
C. Agents impairing mitochondrial ATP synthesis
+
D. Agents causing hydrolysis of NAD(P) in mitochondria
+
I. By increasing NAD(P) availability via oxidation of NAD(P)H
1. Directly: alloxan
2. Enzymatically: z-BHP, NAPBQI, divicine, fatty acid hydroperoxides,
menadione, MPP +
II. By activation of "NAD-glycohydrolase": phenylarsine oxide,
gliotoxin, NO*
DCE = 1,1-dichloroethylene; £~BHP = f-butyl hydroperoxide;
MPP+ = l-methyl-4-phenylpyridinium; NAPBQI = N-acetyl-p-benzoquinoneimine.
Source: Modified from Gregus and Klaassen. S9