Microsomal enzymes, activity

Evidence suggests that endosulfan can induce microsomal enzyme activity. Increased liver microsomal cytochrome P-450 activity was observed in male and female rats after single and multiple administrations of endosulfan (Siddiqui et al. 1987a Tyagi et al. 1984). Increased enzyme activity was observed in hepatic and extrahepatic tissues. Based on the increase in aminopyrine-A-demethylase and aniline hydroxylase activity, endosulfan has been shown to be a nonspecific inducer of drug metabolism (Agarwal et al. 1978). 

Moffitt, A.E., Jr. and S.D. Murphy. 1973. Effect of excess and deficient copper intake on rat liver microsomal enzyme activity. Biochem. Pharmacol. 22 1463-1476. 

PCB Congener and Dose ( mole/kg body weight) Microsomal Enzyme Activity (nmoles product/mg protein/min) ... 

Gallbladder had 85% of radioactivity. Tb 1/2 values were 0.8 days for liver, 3.3 days for intestine, 3.5 days for gallbladder, and 8.2 days for liver Diets rich in fish oils produced marked increases in activities of P-450 cytochromes, 7-EROD, and other enzyme activities bass fed diets devoid of fish oil had lower microsomal enzyme activities... 

Hunter J, Maxwell JD, Stewart DA, et al. 1972. Increased hepatic microsomal enzyme activity from occupational exposure to certain organochlorine pesticides. Nature 237 399-401. 

Walter Reed-Wistar and Charles River male adult rats were exposed to oral doses of turpentine or to turpentine vapors, which consisted of a- and p-pinene. These exposures were followed by oral administration of heptachlor epoxide or of one of three pesticides, paraoxon, heptachlor, or parathion, or by an intraperitoneal injection of hexobarbital. The studies revealed that pretreatment with turpentine reduced hexobarbital sleeping time, reduced the parathion LDso, and increased the heptachlor LDso. The paraoxon and heptachlor epoxide LOo values were unchanged. a-Pinene and P-pinene vaporized from turpentine had no effect on either hexobarbital sleeping time or parathion, paraoxon, or heptachlor epoxide mortality but did increase the heptachlor LDso (Sperling et al. 1972). The authors speculated that increases in hepatic microsomal enzyme activity are responsible for these differences. 

Dichlorobenzidine is an effective inducer of its own metabolic activation (Iba 1987a). The enhancement of 3,3 -dichlorobenzidine mutagenesis has been associated with the induction of cytochrome P-450d (Iba and Thomas 1988), and may result in the elevation of its carcinogenicity. In other animal studies, 3,3 -dichlorobenzidine was also shown to be a potent inducer of hepatic microsomal enzymic activities mediated by cytochrome-P-448 and P-450 (Iba and Sikka 1983 Iba and Thomas 1988). Consequently, it has been suggested that the hepatocarcinogenicity of 3,3 -dichlorobenzidine may be due, at least in part, to the induction of hepatic cytochrome P-488 and DNA-adduction. 

Markers for Dynamic Hepatic Function Monitoring by Microsomal Enzyme Activity... 

There was no effect on hexobarbital-induced sleep times in rats exposed continuously to 225 ppm 2-hexanone (purity not stated) for 7 days (Couri et al. 1977). Thus, 2-hexanone exposure under these conditions does not seem to affect the hepatic microsomal enzyme activities associated with this response. No histopathological effects were seen in the livers of rats exposed to 50 ppm 2-hexanone (purity not stated) for 6 months (Duckett et al. 1979). However, no additional data on potential hepatic effects were found. 

The biodisposition of sedative-hypnotics can be influenced by several factors, particularly alterations in hepatic function resulting from disease or drug-induced increases or decreases in microsomal enzyme activities (see Chapter 4). 

McCormack KM, Hook JB. 1982. Effects of lactation and nursing on tissue concentrations of poly brominated biphenyls and on microsomal enzyme activity in mammary gland and liver in maternal rats. EnvironRes 27 110-117. 

Thus, rats fed on low-protein diets (5%) show a marked loss of microsomal enzyme activity when compared with those animals fed a 20% protein diet (Table 5.19). The decline in... 

It is postulated that this ultimate carcinogen reacts covalently with nucleic acids, producing nucleic acid adducts. It has been demonstrated that benzo[a]pyrene reacts covalently with nucleic acids in vitro, provided that the microsomal enzyme systems necessary for activation are present, and also in whole cell systems. The 7,8-dihydrodiol metabolite of benzo [alpyrene binds more extensively to DNA after microsomal enzyme activation than does benzo [alpyrene or other benzolalpyrene metabolites, and the nucleoside adducts formed from the 7,8-dihydrodiol of benzolalpyrene are similar to those obtained from cells in culture exposed to benzolalpyrene itself. Furthermore, the synthetic 7,8-diol-9,10-epoxides of benzo [alpyrene are highly mutagenic in mammalian as well as in bacterial cells. 

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