Lysosomal membrane stability

One of the characteristic cellular changes occurring following chemical exposure is the increased fragility of the lysosomal membrane. Lowe el al. (1992) developed an in vitro technique to measure the stability of the lysosomal membrane in isolated liver cells in fish caught in clean and contaminated sites. The technique was based on the ability of cell lysosome to retain neutral red dye. On the basis of this technique, further modifications were implemented by Weeks and Svendsen (1996) to enable use with terrestrial invertebrates. This method (the neutral red retention time assay) has since been applied widely for measuring lysosomal damage. 

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Immunopathology Hematology (blood cell count), weight of spleen, thymus and liver, histology of spleen, thymus, and lymph nodes Histopathology, cell viability, lysosomal membrane stability... 

Kato Y, Kudo M, Shinkawa T, Mochizuki H, Isaji M, Shiromizu I, et al. Role of O-linked carbohydrate of human urinary trypsin inhibitor on its lysosomal membrane-stabilizing property. Biochem Biophys Res Commun 1998 243 377-383. 

These are tests that are established within the academic community as monitors of chemical exposure and chemical effect. Unlike the procedures discussed in section 6.2, standards do not exist for these tests. Development instead can be tracked via a series of scientific papers. Some methods are long established in soil ecology and ecotoxicology. Examples include invertebrate bioassays, soil enzyme assays and litterbags. In contrast, a number of methods, such as bait lamina and some biochemical assays (e.g. lysosomal membrane stability), have been developed more recently but have passed quickly into widespread use. 

Accepting that the absence of an international guideline should not be a barrier to the use of developing methods, further useful methods can be identified. Some, such as the bait lamina (Tome, 1990a) and earthworm lysosomal membrane stability assay (Weeks and Svendsen, 1996), are now well established in the scientific literature and appear particularly suited to assessing exposure and effects. Some of the biomarker techniques, such as ChE inhibition, metallothio-nein induction and possibly immune function assessment, can be used to provide valuable information regarding the nature of the chemicals present and the exposure of soil species. 

Epileptic patients also have elevated blood copper concentrations [302-304]. As shown in Table 6.1, the brain contains more copper than any other nonstorage tissue in the human body [2], and brain tissues are known to require copper-dependent enzymes listed in Table 6.2 for normal development and function [ 1,8,135]. In addition, it has been pointed out that copper-dependent processes are required for modulation of prostaglandin syntheses [135], lysosomal membrane stability [135], and the activity of histamine (see previous Section on gastrointestinal ulcers), which are also important for normal brain functions. 

Ibuprofen causes a lysosomal membrane stabilizing effect. This may help to protect myocardial integrity during ischemia. 

Some recent investigations have failed to substantiate earlier claims that NAA are effective as a result of, helr ability to stabilize lysosome membranes. It has been concluded, however, that lysosome membrane stability is very much dependent on experimental conditions and that in vitro methods using rat liver lysosomes are not sufficient for studying the effect of antiinflammatory drugs. Increased lysosomal enzyme activity in homogenates of rat paws paralleled increases in paw volume in rats with adjuvant-induced arthritis. Oral administration of phenylbutazone arrested Increases in both enzyme activity and paw edema. Above normal lysozyme activity was found in the serum and synovial fluid of a signlficent proportion of patients with RA. ... 

Recent pharmacological and biochemical studies have provided evidence for five plausible Cu-dependent mechanisms of action which may account for the observed biologic activity of Cu complexes. These are induction of lysyl oxidase or lysyl oxidase mimetic activity, induction of superoxide dismutase or superoxide dismutase mimetic activity, modulation of prostaglandin synthesis, modulation of histamine activity, and lysosomal membrane stabilization. Ongoing research may provide evidence for still other Cu-dependent processes which may more fully explain the biologic activity of Cu complexes. 

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