Detoxification hepatic pathways

Wagner M, Halilbasic E, Marschall HU, et al. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 2005 42 420-430. 

After intravenous administration, paclitaxel is extensively distributed, despite extensive binding to plasma proteins (89%), presumably albumin (2). Its routes of elimination have not been fully elucidated, but renal clearance accounts for an insignificant proportion of total systemic clearance, suggesting that metabolism, biliary excretion, or excretion via other routes are responsible for elimination (6). High concentrations of paclitaxel and its hydroxylated metabolites have been found in rat and human bile, suggesting hepatic metabolism (8). In all, 11 metabolites of paclitaxel have been identified, and paclitaxel metabolism to 6-a-hydroxypaclitaxel is an important detoxification pathway (6,9). 

Paracetamol (known as acetaminophen in the USA) is N-acetyl-para-aminophenol (Figure 25.11). It has the same detoxification pathways as phenol and also carries the risk of inducing methemoglobinemia. To be on the safe side, it should not be used as an intravenous analgesic during a full-face phenol peel, so as not to saturate the detoxification pathways. Paracetamol is also an intermediate in the pathway for detoxification of aniline derivatives, before hepatic glucuronide and sulfate conjugation allow them to... 

Lip Eyelid formula is a phenol peel that I first developed to increase dermatological safety and to achieve results without any occlusion on the sensitive skin of the eyelids. The same solution was then applied to the wrinkles around the mouth and then to the whole face, but with 24 hours occlusion in these two indications. It is an oil solution of phenol at over 60%. Four different oils are used in the various stages of the product s preparation. The aim of the oily formulation is to slow down the penetration of the phenol through the skin and to improve dermal and epidermal maceration. It limits the toxicity of phenol by saturating the biochemical hepatic detoxification pathways more slowly. 

An early observation about endogenous functions of PXR and CAR has been their implication in hepatic bile acid metabolism [48,49]. Most of the more recent findings on this topic are summarized in a number of reviews [9,50-52]. Briefly, CAR and PXR have been shown to play overlapping but not identical roles in hepatic bile acid detoxification [53,54]. Recent work has also drawn attention to the importance of PXR in cholesterol detoxification in the liver, kidney and intestine [55-59]. Both CAR and PXR are involved in bilirubin metabolism and clearance [60] activation of these pathways is of potential therapeutic interest in jaundice and chronic arthritis [61]. 

Wagner, M., Halilbasic, E., Marschall, H. U., Zollner, G., Fickert, P., Langner, C., Zatloukal, K., Denk, H., and Trauner, M. (2005) CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 42, 420 130. 

The specific mechanisms by which individual dietary components can alter the cancer process remain poorly understood. However, mechanisms underlying the carcinogenesis process are understood sufficiently so that model systems to evaluate the ability of a specific compound to inhibit or promote processes that may prevent or delay cancer development can be predicted. Phytochemcials can act at a variety of sites relevant to the development of the cancer cells. They may inhibit carcinogen activation, induce hepatic detoxification pathways, exert antioxidant effects/metal chelation properties, enhance immune response, induce apoptosis, and alter hormonal environment. 

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