Cellular necrosis

Sodium iodide 131 is an oral liquid that concentrates in the thyroid and initially disrupts hormone synthesis by incorporating into thyroid hormones and thyroglobulin. Over a period of weeks, follicles that have taken up RAI and surrounding follicles develop evidence of cellular necrosis and fibrosis of the interstitial tissue. 

The normal range (i.e., before ECT) of pH values was 6.5 -8.7. A pH of less than 6 (at the anode) or more than 9 (at the cathode) reflected total cellular necrosis in those areas.90 To elucidate the possible complications that may arise during ECT in... 

O.lOg/%, which is approximately five times more toxic than the nonchlorinated mononi-troparaffin. Rabbits exposed to 2 600 ppm for 2 hours died, but 2 2 00 ppm for 1 hour was non-lethal. Effects included irritation of the eyes and mucous membranes, and autopsy revealed pulmonary edema and cellular necrosis of the heart, liver, and kidneys. 

TCE carcinogenesis may require exposure to high doses sufficient to cause cellular necrosis. Repeated cycles of necrosis and regeneration would occur with the emergence of hyperplasia and then neoplasia. Low exposures commonly encountered in human studies are not sufficient to initiate the carcinogenic process. 

The cascade of biochemical events described above enhances the cellular necrosis and tissue breakdown, leading to what meat scientists and food technologist call meat-tenderization. Since muscle is primarily protein in nature and since hydrolytic, and specifically proteolytic, activity increases during postmortem aging, muscle represents a remarkable pool of material for the production of flavor peptides and amino acids as well as other precursors for flavor development (2). 

Chemical aggression, which is translated by a cellular necrosis... 

This is similar to the highly selective action of oxygen removal from Fe by means of CO (carbon monoxide) or the intoxication of the metabolic breathing by CN (cyanide ion). All these specific types of intoxications systemically result in ceasing of local metabolic activity with consecutive cellular necrosis. 

In conclusion, the pulmonary toxicity of 4-ipomeanol seems to be due to metabolic activation probably by formation of an unstable epoxide on the furan ring catalyzed by CYP4B1 in the Clara cell. The epoxide can rearrange to an a, 3 unsaturated dialdehyde (Fig. 7.37), which can interact with macromolecules and covalently bind, leading to cellular necrosis and edema. 

Fibrosis resulting in the loss of normal organ structures is the hallmark of chronic rejection. The fibrosis may be due to wound healing, which is then followed by the cellular necrosis of acute rejection. However, it must be pointed out that chronic rejection develops many times in the absence of acute rejection. Fibrosis may be a result of several diverse factors such as equation of chronic rejection with chronic delayed-type hypersensitivity reaction, injury to blood vessels and resulting response to chronic ischemia, the proliferation of smooth muscle cells in the intima of arterial walls producing vascular occlusion, or persistent viral infections that will induce cellular immune response. 

Meegan et al. reported the synthesis of a number of [3-lactams and these were evaluated in a series of in vitro assays, which determined their antiproliferative activity in MCF-7 and MDA-MB-231 breast cancer cell lines and also their affinity for the oestrogen receptor (Fig. 6). The cytotoxicity of the [3-lactams was determined in the LDH assay to establish that the antiproliferative effects observed were due to cytostasis rather than cellular necrosis. Most of the compounds demons-treated low cytotoxicity, indicating that their action is cytostatic rather than cytotoxic. Cytotoxicity values considerably below that obtained for tamoxifen (13.4%, 10 pM) were observed with a most potent compound (3%, 10 pM in MCF-7 cell... 

As mentioned previously, most reactive metabolites are electrophiles that can bind covalently to nucleophilic sites on cellular macromolecules such as proteins, polypeptides, RNA, and DNA. This covalent binding is considered to be the initiating event for many toxic processes such as mutagenesis, carcinogenesis, and cellular necrosis, and is discussed in greater detail in the chapters in Parts IV and V. 

Radicals such as CCI3, produced during the oxidation of carbon tetrachloride, may induce lipid peroxidation and subsequent destruction of lipid membranes (Figure 8.3). Because of the critical nature of various cellular membranes (nuclear, mitochondrial, lysosomal, etc.), lipid peroxidation can be a pivotal event in cellular necrosis. 

The precise biochemical mechanisms leading to irreversible cell injury and nephrotoxicity are not well-defined. Many diverse biochemical activities occur within the kidney, and interference with one or more of these functions may lead to irreversible cell injury. Rather than any one single mechanism mediating chemically induced nephrotoxicity, it is likely that a toxicant alters a number of critical intracellular functions, ultimately leading to cytotoxicity and cellular necrosis. 

In the progressing lesion, a number of additional processes come into play, the most important of which are cellular necrosis with the release of foam-cell lipids to the interstitium, and the mitogen-stimulated proliferation of myointimal cells (smooth muscle cells), with the subsequent synthesis of collagens, elastin and proteoglycans. 

Tabas, L, Marathc, S., Keesler, C. A., Beal ini, N., and Shiratori, Y. (1996). Evidence that the initial up-regulation of phosphatidylcholine biosynthesis in free choiesterol-loaded macrophages is an adaptive response that prevents cholcslcrol-induced cellular necrosis. J. Biol Chem. 271, 22773-22781. 

Some cellular necrosis was observed in the liver of male rats receiving a 5% p-CD diet and in female rats receiving a 2.5 and 5.0% p-CD diet. An increase in portal inflammatory cell infiltration was also observed in male rats receiving the 2.5% p-CD diet and male and female rats receiving the 5.0%o p-CD diet. These observations were considered to represent a mild hepa-totoxicity (mechanism unknown), which was further evidenced by increases in serum liver enzymes. 

Ciclosporin can cause cholestasis and cellular necrosis by an inhibitory effect on hepatocyte membrane transport proteins at both sinusoidal and canalicular levels. It induces oxidative stress by accumulation of various free radicals. Ademetionine (5-adenosylmethionine) is a naturally occurring substance that is involved in liver detoxification processes. The efficacy of ademetionine in the treatment and prevention of ciclosporin-induced cholestasis has been studied in 72 men with psoriasis (89). The patients who were given ciclosporin plus ademetionine had low plasma and erythrocyte concentrations of oxidants and high concentrations of antioxidants. The authors concluded that ademetionine may protect the hver against hepatotoxic substances such as ciclosporin. 

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