Xenobiotic-induced toxicity

There are two general approaches to cDNA expression, transient expression and stable expression. Transient expression systems are typically based on a viral vector the host cells are infected with cDNA-bearing virus and the cDNA-derived protein is produced. At some point a maximum level of cDNA-derived protein expression is obtained and the protein is harvested for use in incubations. Viral vectors often have cytopathic effects on the host cells which usually precludes analysis of xenobiotic-induced toxicity to the host cell. Stable expression systems can be based on integrating or episomal vectors. With both stable expression approaches, homogeneous, clonally derived populations of cells stably expressing the cDNA are identified and characterized. The properties, advantages and disadvantages of the two approaches are discussed below. 

Table 5 Examples of Ihe enhanced sensitivities to xenobiotic-induced toxicity of transgenic Nrf2 knockout (Nrf2 ) mice compared to wild-type (Nrf2 ) counterparts...

Foth, H. Role of the lung in accumulation and metabolism of xenobiotic compounds-implications for chemically induced toxicity. Crit. Rev. Toxicol. 25 165-205, 1995. 

Because induction of DMEs can enhance clearance of xenobiotic chemicals, specific agents are being tested for potential prevention of chemically induced toxicity, especially for chemoprevention of cancer. Oltipraz, originally developed as an anti-schistosomal drug, induces multiple Phase... 

Xenobiotic-induced liver injury has become the most frequent cause of acute liver failure in humans in the USA and around the world, exceeding all other causes combined (Watkins and Seef, 2006). Owing to its detoxification mechanisms, the liver protects the individual against xenobiotic-induced injury. Certainly, the liver toxicity caused by chemical warfare agents is a potential area of concern. 

Studies of xenobiotic-induced immune dysregulation in animal models. Hydralazine and procainamide-induced autoimmunity HgClj and gold salt-induced autoimmunity The impact of genetic studies in our understanding of immunological-mediated toxic-induced renal disease ... 

Almost all of the work examining modulation of xenobiotic-induced hepatotoxicity in diabetes has been done using type 1 diabetic models. Recently, a study reported a novel high-fat diet-induced type 2 diabetic rat model and tested the susceptibility of these diabetic rats to several classical hepatotoxicants. On treatment with nonlethal or sublethal doses of allyl alcohol, CCI4, or thioacetamide, it was found that hepatotoxicity of all these toxicants is significantly increased in the type 2 diabetic rats. 

It is universally accepted that ionizing and UV electromagnetic radiation induce toxic effects in man. It has been shown above that these toxic effects are exacerbated when irradiation is coupled with xenobiotic exposure. Conversely, the toxic effects of xenobiotic exposure are enhanced by simultaneous exposure to ionizing or UV radiation. 

Given the multiple metabolic functions performed by the liver, it should not be surprising that the hepatotoxic effects of xenobiotics are so different several different morphological patterns of xenobiotic-induced hepatotoxicity can be observed (Plaa 1991 Batt and Ferrari 1995 Zimmerman 1999 Plaa and Charbonneau 2001 Kaplowitz 2002 Kaplowitz and DeLeve 2003 Lee 2003). For example, in acute toxicity, cell degeneration leads to necrosis (cell death), and this may or may not be accompanied by steatosis (an accumulation of lipids and fatty liver where hepatic lipid content is >5%). Necrosis may affect small groups of hepatocytes (i.e., focal... 

The health of the placenta is a prerequisite for the health of the fetus. Consequently, any xenobiotic-induced damage to the placenta may cause damage to the fetus. Thus, it is very important to identify xenobiotics damaging the placenta and to elucidate their mechanisms of action associated with the toxicity, Furthermore, placentas of mothers with certain... 

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