Leucocytes, toxicity

Tests have been published for determining toxicity towards leucocytes. Evaluation on the infected chorioallantoic membrane of hens eggs was suggested as being a useful method of testing potential wound disinfectants. 

Unlike the liver injury that occurs with toxic chemicals (see above), reperfusion injury affects not only the hepatocytes but also the endothelial cells that line the sinusoids as an important primary target. It is thought that there may be some aspects of preservation-reperfusion injury that are unique to the liver and UW solution is apparently more effective in this tissue than in others (Clavien aal., 1992). The principle characteristic of this injury is that it involves damage to the sinusoidal cells such that leucocytes and platelets are stimulated to adhere on reperfusion. 

Invasion of the tissues by an infective agent initiates an inflammatory response in the animal. This is non-specific and is mediated primarily by substances released from tissues that are damaged as a result of either trauma or the toxic effects of the infective agent. The major mediator is the vasoactive amine histamine, which causes an increased local blood flow and capillary permeability, resulting in local oedema. A major aspect of the inflammatory response is the involvement of large numbers of phagocytic cells, particularly the polymorphonuclear leucocytes. These are chemotactically attracted to the inflamed tissues and are mainly responsible for the elimination of particulate material. This often results in the destruction of many of these cells and the formation of pus. 

Toxicity by metabolism is not confined to the liver since oxidative systems occur in many organs and cells. Amodiaquine is a 4-aminoquinoline antimalarial that has been associated with hepatitis and agranulocytosis. Both side-effects are probably triggered by reactive metabolites produced in the liver or in other sites of the body. For instance polymorphonuclear leucocytes can oxidize amodiaquine. It appears that amodiaquine is metabolized to a quinone imine by the same pathway as that seen in... 

On repeated administration of the preparation to healthy rats at a 100 mg/kg dose with a break for 72 hours no toxic signs were observed. After 5 injections the weight of the animals increased by 34.6% and after 10 injections by 69.5%. The amount of leucocytes in peripheral blood increased from 8900 to 13600 per mm3 after 5 injections and remained at this level until the injections were stopped. (The preparation was injected per os as a suspension in 1% starch paste). 

Pirmohamed M, Coleman MD, Hussain F, Breckenridge AM, Park BK. Direct and metabolism-dependent toxicity of sulphasalazine and its principal metabolites towards human erythrocytes and leucocytes. Br J Clin Pharmacol 1991 32(3) 303-10. 

Came and coworkers have described a toxic lipid extracted from Coryne-bacterium ovis, a pathogen which, in sheep, causes a wide-spread disease known as caseous lymphadenitis. The lipid extracted from living C. ovis with petroleum ether is toxic for leucocytes in vitro. A preliminary chemical investigation of this lipid fraction, kindly prepared by Dr. Came, has not yet yielded definite information about the chemical nature of the active fraction. A synthetic 6,6 -dicorynomycolate of trehalose, prepared by Diara and Pudles, has been found devoid of leucotoxic action. 

Evaluation of radiotoxicity in animals receiving 1.1-2.3 GBq of Re-HEDP was performed by counting two parameters, namely, the number of leucocytes and thrombocytes for bone marrow toxicity and the blood... 

Trichocethecens possess a range of toxic effects. The acute trichocethecen toxicity manifests as intestine disorders (vomiting, temperature, diarrhoea etc.). There are also haematological effects such as anemia and reduction of the number of leucocytes. These toxins suppress the synthesis of proteins in the organism. 

The metabolism of the antidepressant drug mianserin (41) (Fig. 13.35) revealed analogies and differences with disopyramide. Indeed, aromatic oxidation in human liver microsomes occurred more readily for the (S)-enantiomer, whereas N-demethylation was the major route for the (/ )-enantiomer. At low drug concentrations, cytotoxicity toward human mononuclear leucocytes was caused by (J2)-miansejrin more than by (S)-mianserin and showed a significant correlation with N-demethylation (176). Thus, the toxicity of mianserin seemed associated with N-demethylation rather than with aromatic oxidation, in contrast to disopyramide. The chemical nature of the toxic intermediates was not established, but a comparison between disopyramide and mianserin emphasizes that no a priori expectation should influence toxicometabolic studies. 

Toxicity of heparin and heparinoids has been examined in considerable detail from the standpoint of immediate and long-term toxicity. Initial and long-term toxicity of heparinoids is relatively slight with the initial material before sulphonation, but the introduction of sulphuric acid groups into the polysaccharide results in considerable toxicity. The effect of a series of polysaccharides and their sulphonated derivatives on leucocyte count, body temperature and E.S.R. in rabbits was that homopolar unbranched corn-... 

What is now the nature of these three factors for immunity We do not know. All that we can say is that on the one hand alexin or cytase appears to come from the cells, and especially from leucocytes whose important rdle in phagocytosis is known, and that on the other hand all the antigens, in spite of their great diversity, bear a certain relation to the albuminoids. Thus the vegetable toxins and the pdbons, protein in nature, are still capable of producing antibodies, while the alkaloids, likewise toxic for the cells but of quite different chemical nature, do not... 

Many of the other products of uric acid noted above are toxic and are not considered to be normal metabolites in the human. However, the possibility certainly exists that conditions associated with peroxidatic oxidation of uric acid such as large accumulations of leucocytes (localized abscesses, leucocytic exudates, leukemia, etc.) could give rise to toxic substances. Thus, there is a real need to understand the basic mechanism of enzymic oxidations of uric acid. Our understanding of this mechanism has been drawn from chemical, enzymic, and electrochemical studies. Because this review is primarily concerned with the electrochemistry of biomolecules, the electrochemical behavior of uric acid will be discussed first. 

Because blood is a multicomponeiit system containing a large number of ionized and molecular species differing in size, mass, cell structure, and coUoidal particles, several processes such as polymerization of blood proteins, reaction with biosurfactants, and other accompanying processes besides adsorption can take place on the surface of adsorbent carbon. These processes can influence the adsorptive removal of toxics and other harmful components from blood during hemoperfusion. Furthermore, experiments concerning destraction of thrombocytes and deposition of platelets and leucocytes on the adsorbent carbon surface can only be carried out on animal blood. 

The toxicity of insoluble manganese dioxide dusts depends on the particle surface area as demonstrated in vitro by lactate dehydrogenase release from NMRI mouse peritoneal macrophages elicited by casein hydrolysate (Lison et al. 1997). In vivo, the lung inflammatory response was assessed by analysis of bronchoalveolar lavage after intratracheal instillation in mice (LDH activity and protein concentration in the cell-free fraction, recruitment of polymorphonuclear leucocytes). Freshly ground particles with a specific surface area of 5 mVg in... 

In patients with chronic renal failure, the bone marrow is generally hypercellular with a shift to the left - as in toxic conditions. The neutrophilic leucocytosis in the peripheral blood is accompanied by a shift to the right in the granulocytic series to include many segmented neutrophils (12). Whether this would account for the increased glycine incorporation into purines in leucocytes of patients with chronic renal failure is entirely speculative. 

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