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Renal Drug-Metabolizing Enzymes in Experimental Animals and Humans
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Supplementation of the diet of rats with 10% lauric acid enhanced the concentration of cytochrome P-450 and the activity of ω-oxidation (Jakobsson et al., 1970). Similarly, treatment with benzo(a)pyrene or methylcholanthrene (P-450 I Al family) led to a marked increase in aryl hydrocarbon hydroxylase activity in renal cortical microsomes (Gelboin and Blackburn, 1964; Nebert et al., 1972; Grundin et al., 1973; Jakobsson et al., 1973; Guengerich and Mason, 1979; Christou et al., 1987) and treatment with polychlorinated biphenyls (Arochlor 1254, a mixture of planar and nonplanar isomers), polybrominated biphenyls, β-naphthoflavone, and isosafrole also induce renal cytochrome P-450 and activity with various substrates (Kluwe et al., 1978; Kluwe and Hook, 1981; Alvares and Kappas, 1977; McCormack et al., 1978; Hook et al., 1982; Wolf et al., 1983). In contrast, treatment with phenobarbital had no effect on the cytochrome P-450 content or the activity with various substrates (Uehleke and Greim, 1968; Jakobsson et al., 1970; Muller et al., 1973; Guengerich and Mason, 1979; Kluwe and Hook, 1981; Lister and Virgo, 1982; Hasumura et al., 1983; Christou et al., 1987). The rat kidney was also refractory to a nonplanar polychlorinated biphenyl, 2,4,2′,4′-tetrachlorobiphenyl (Hook et al., 1982), which produces a pattern of induction in rat liver similar to that produced by phenobarbital (Goldstein et al., 1977) and is sufficiently lipid soluble to persist in tissues for some time (Brandt, 1977).
Effects of Environmental Factors on the Endocrine System
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
The process of implantation requires proper interactions between progesterone and estrogen. Analogs of LHRH and steroids or other compounds interfering with progesterone or estrogen are found to affect implantation. For example, DDT analogs and polychlorinated biphenyl (PCB) compounds are insecticides with estrogenic properties. In mice, they have been shown to prolong pregnancy or reduce the number of implantation sites. Ions of heavy or transition metals such as cadmium, copper, and zinc inhibit the binding of estrogen, leading to implantation failure.
The role of lifestyle factors in recurrent implantation failure
Published in Efstratios M. Kolibianakis, Christos A. Venetis, Recurrent Implantation Failure, 2019
Vicki Nisenblat, Robert J. Norman
Atrazine is the most common pesticide suspected to have an EDC effect. It is widely used in commercial agriculture and remains in soil and water for a long time. The use of another once commonly used pesticide, dichloro-diphenyl-trichloroethane (DDT), has been banned for years in many countries, but it persists within the environment for decades due to resistance to degradation. Unfiltered drinking water is the main source of contact, and there is a possibility for occupational exposure in individuals who work with pesticides or in pesticide-treated areas.
Concentration dependence of human and mouse aryl hydrocarbon receptor responsiveness to polychlorinated biphenyl exposures: Implications for aroclor mixtures
Published in Xenobiotica, 2019
Hongxue Shi, Josiah E. Hardesty, Jian Jin, Kimberly Z. Head, K. Cameron Falkner, Matthew C. Cave, Russell Allen Prough
PCBs are polyhalogenated aromatic hydrocarbons and consist of up to 10 chlorine atoms attached to a biphenyl ring. PCBs were manufactured as mixtures (US tradename Aroclor) and sold by the percentage of chlorine in the mix. For example, Aroclor 1254 is 54% chlorine by mass, while Aroclor 1260 is 60% chlorinated. Of the 209 theoretical PCB congeners, approximately 130 were present in commercial PCB mixtures. PCB mixtures were used in a variety of industrial applications, such as insulating agents for electrical transformers. Approximately 1.3 million tons were produced worldwide before PCBs were banned (Ockenden et al., 2003). The primary routes of human PCB exposure are ingestion of contaminated food (Schecter et al., 2003) or breast milk, and inhalation of contaminated air (Ampleman et al., 2015). PCB metabolism varies considerably with low molecular weight PCBs being metabolized at a higher rate than the more heavily chlorinated PCBs. This leads to bioaccumulation patterns in adipose that greatly favor retention of the more highly chlorinated congeners being similar to those present in Aroclor 1260. However, there is an important exception. Aroclor 1260 is not believed to contain significant amounts of DL PCBs (Battelle Memorial Institute, 2012; Wahlang et al., 2014a; Wahlang et al., 2014b).
Biphenyl-induced cytotoxicity is mediated by an increase in intracellular Zn2+
Published in Drug and Chemical Toxicology, 2019
Masamichi Ae, Naohiro Imura, Tomoko Inubushi, Shin Abe, Bekki Yusuke, Mayumi Sugimoto, Norio Kamemura
Postharvest treatment prevents physical and chemical changes that negatively modify the quality of fruits and vegetables during processing, storage, and transport (Gustavo et al.2003, Dave et al.2017, Chu et al.2018). In Japan, ortho-phenylphenol, biphenyl and thiabendazole are commonly used as postharvest treatments (Ministry of Health, Labour and Welfare 2009). Biphenyl is naturally generated in coal tar, stock, and natural gas (IPCS 1999, HSDB 2014, Li et al.2016). Several studies have shown that the toxic effect of biphenyl is lower than that of other fungistats used for postharvest treatment (Nakagawa et al.1993, Sasaki et al.1997). Biphenyl residue is allowable in foods at concentrations below 0.07 g/kg according to the Ministry of Health, Labour and Welfare in Japan (2009). In addition, according to the U.S. Environmental Protection Agency, the acceptable daily intake (ADI) of biphenyl is 0.05 mg/kg body weight (BW)/d for oral exposure (U.S. EPA 2013, Danish EPA 2015). Therefore, the use of biphenyl is accepted worldwide.
A precise, sensitive and stable LC-MSMS method for detection of picomolar levels of serum aldosterone
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2018
Margrete Lie, Ketil Thorstensen
After implementation of the method for routine use, we found, through monitoring of qualifier ratios, an analyte co-eluting with aldosterone in 3–5% of patient samples. The unknown analyte is not normally present in human serum since it is observed in only 3–5% of the samples. Further investigation revealed that all patients with this interference had been medicated with prednisolone. Moreover, the concentration of the unknown analyte apparently corresponded with the prednisolone dosage. Thus, one may speculate that this is a metabolite of prednisolone. Resolution of this analyte was successfully handled with an alternative method (see Supplementary Method file). The alternative method utilises a longer biphenyl column and a different elution gradient compared to the original method. This gives good chromatographic separation between the interfering peak and aldosterone, which is now presenting with correct qualifier ratios. Due to the fact that this affects a very small fraction of samples we chose to keep our original method for routine use since the alternative method has a longer total run time of 8.5 min, and a slightly lower analytical sensitivity. All samples presenting with this interference are routinely re-analysed with the alternative method. During the period, our method has been in routine use (approximately 3 years), we have observed no other interfering analytes than the previously mentioned one. Although the interfering analyte is still unidentified, it is easy to detect and exclude, and precise quantification of aldosterone is obtained with the alternative method.