Xenobiotic stress

C. L. Crowley-Weber, K. Dvorakova, C. Crowley, H. Bernstein, C. Bernstein, H. Garewal and C. M. Payne, Nicotine increases oxidative stress, activates NF-kappaB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxy-cholate relevance to colon carcinogenesis, Chem. Biol. Interact., 2003, 145(1), 53. 

Versteeg, D.L., Graney, R.L. and Giesy, J.P. (1983) Field utilization of clinical measures of xenobiotic stress in aquatic organisms. In Aquatic Toxicology and Hazard Assessment, Vol. 10, ASTM STP 971, Adams, W.J., Chapman, G.A. and Landis, W.G. (eds), pp. 289-306. American Society for Testing and Materials, Philadelphia, PA. 

Fishelson, L., A. Yawetz, A.S. Perry, Z. Zuk-Rimon, R. Manelis, and A. Dotan. 1994. The Environmental Health Profile (EHP) for the Acre Valley (Israel) xenobiotics in animals and physiological evidence of stress. Sci. Total Environ. 144 33-45. 

Laskin, J. D., Heck D.E., and Laskin D.L. The ribotoxic stress response as a potential mechanism for MAP kinase activation in xenobiotic toxicity. Toxicol. Sci. 69, 289, 2002. 

Our questions broadened to consider how the transport and metabolic capabilities of these aquatic species compare with those of mammalian species. One reason for asking such a question is to assess whether the presence or absence of these capabilities alters the ability of fish to survive in toxic environments. Survival mechanisms fall into two catagories - behavioral and physiologic. An example of a behavioral mechanism could be as simple as a fish avoiding that area of a stream which contains toxic quantitites of phenol. When external perturbations caused by pollutants are small, homeostatic mechanisms such as those of the liver and kidney, allow fish to adapt to the body of water in which they exist. The problem then is related to defining the limits to which homeostatic phenomena can be stressed in aquatic species. An important reason to establish such information in fish is that bodies of water are the "ultimate sink" for a number of pollutants (12). Thus, while a behavioral response such as removing itself from a toxic environment is invariably available to a mammalian species, this type of response is impossible for a fish if a toxic xenobiotic occurs uniformly throughout an entire body of water. 

Supernumerary rib is an expected morphological observation in developmental toxicity studies and one of the most common skeletal variants in rodents and rabbits with highly variable incidence between species and strain. The interpretation of supernumerary rib data can be complex because not only is this a spontaneously occurring variant in normal fetuses but it is also induced in rats and mice by various experimental conditions, including increased maternal stress (27) or high dosages of xenobiotics (14, 28, 29). 

There are many factors, both chemical and biological, which affect the disposition of xenobiotics. Chemical factors include size and structure, pKa, chirality, and lipophilicity. Biological factors include species, sex and strain, genetic factors, hormonal influences, disease and pathological conditions, age, stress, diet, dose, enzyme induction and inhibition, and tissue and organ specificity. All of these factors can affect the toxicity of a chemical by changing its disposition, especially its metabolism. 

Because endogenous factors also affect the enzymes of xenobiotic metabolism, the toxic sequelae to be expected from a particular toxicant will vary with developmental stage, nutritional statue, health or physiological status, stress or environment. 

Pedrajas, J.R., J. Peinado, and J. LopezBarea. 1995. Oxidative stress in fish exposed to model xenobiotics. Oxidatively modified forms of Cu, Zn superoxide dismutase as potential biomarkers. Chem. Biol. Interact. 98 267-282. 

Many of the factors that can affect organisms adversely are inherent stressors, including availability of nutrition, water quality, temperature and other climatic extremes, disease, and predation. It is important to be able to separate effects of inherent stressors from those of toxic chemicals. There are often important synergistic relationships between inherent stressors and the effects of toxic chemicals. Organisms that are under stress from inherent stressors are likely to be more susceptible to the effects of xenobiotic toxicants. 

Fig. 3.5 Metabolism of 2 furnishes 118 metabolites via 25 different pathways ofwhich those are depicted in this scheme that are gluthatione (GSH) dependent. From the exemplary biotransformation of 2 can be inferred that besides stereoselective reduction there exist competing pathways in S. cerevisiae as a result of xenobiotic cell stress (/) stereoselective reduction,...

Two genetically distinct heme oxygenases (HOs) have been characterized HO-1 is an inducible form, whereas HO-2 is constitutive. HO-2 is abundant in selective tissues such as brain and the cardiovascular system. HO-1 is highly inducible in many tissues in response to a variety of stresses, including infection, exposure to xenobiotics, hypoxia, and proinflammatory cytokines. The recognition that heme oxygenase is expressed in many different tissues led to studies of the role of heme degradation apart from the pathway for formation and elimination of bilirubin derived from destruction of senescent erythrocytes. 

Transcription is activated by xenobiotic metabolites and oxidative stress. 

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