A simple and sensitive assay of 7-ethoxycoumarin deethylation

Separation and characterization of highly purified forms of liver microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls, phenobarbital, and 3-methylcholanthrene.

http://www.renewablefarming.com/images/2015Images/2015PDF/20150815-glyphosate-toxic.pdf

Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.

Glyphosate [N-(phosphonomethyl) glycine] is a broad spectrum, post emergent herbicide and is among the most widely used agricultural chemicals globally. Initially developed to control the growth of weed species in agriculture, this herbicide also plays an important role in both modern silviculture and domestic weed control. The creation of glyphosate tolerant crop species has significantly increased the demand and use of this herbicide and has also increased the risk of exposure to non-target species. Commercially available glyphosate-based herbicides are comprised of multiple, often proprietary, constituents, each with a unique level of toxicity. Surfactants used to increase herbicide efficacy have been identified in some studies as the chemicals responsible for toxicity of glyphosate-based herbicides to non-target species, yet they are often difficult to chemically identify. Most glyphosate-based herbicides are not approved for use in the aquatic environment; however, measurable quantities of the active ingredient and surfactants are detected in surface waters, giving them the potential to alter the physiology of aquatic organisms. Acute toxicity is highly species dependant across all taxa, with toxicity depending on the timing, magnitude, and route of exposure. The toxicity of glyphosate to amphibians has been a major focus of recent research, which has suggested increased sensitivity compared with other vertebrates due to their life history traits and reliance on both the aquatic and terrestrial environments. This review is designed to update previous reviews of glyphosate-based herbicide toxicity, with a focus on recent studies of the aquatic toxicity of this class of chemicals.

Impact of glyphosate and glyphosate‐based herbicides on the freshwater environment

DDT, DDE, and DDD ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: V FOmWORD This toxicological profile is prepared in accordance with guidelines* developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the hazardous substance described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's reIevant toxicological properties. Following the public health statement is information concerning levels of si,gnificant human exposure and, where known, significant health effects. The adequacy of information to determine a substance's health effects is described in a health effects summary. Data needs that are of significance to protection of public health are identified by ATSDR and EPA. Each profile includes the following: The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chronic health effects; and Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans. principal audiences for the toxicological profiles are health professionals at the federal, state, and local levels; interested private sector organizations and groups; and members of the public. …

/pdf/toxicological-profile-for-ddt-dde-and-ddd-2zxtxz16v4.pdf

Toxicological profile for DDT, DDE, and DDD

Microsomes were prepared from the liver, kidney and lung of phenobarbital or 20–methylcholanthrene treated and control rats with the conventional ultracentrifugation and calcium aggregation methods. The two methods were compared as to the yield of microsomal protein, amount of cytochrome P–450/448 and activity of UDPglucuronosyltransferase, benzopyrene hydroxylase and p–nitroanisole O–demethylase. The absolute amount of cytochrome P–450/448 (nmol/g wet weight), as well as the enzymatic activities dependent on it (nmol produced/g wet weight) did not differ significantly in any tissue of either treated or control animals nor did that of UDPglucuronosyltransferase. However, the ultracentrifugation method resulted in a slightly smaller yield of the hepatic microsomal protein and a correspondingly higher yield of cytochrome P–450/448 per mg protein as well as higher specific enzymatic activities of both the consecutive drug biotransformation reactions studied. The specific activity of UDPglucuronosyltransferase in digitonin treated microsomes was twice as high in the conventional microsomes as in the calcium aggregated microsomes; no differences was found in the trypsin treated microsomes. The specific activity of the hepatic benzpyrene hydroxylase of the benzpyrene treated animals in the calcium harvested microsomes was 55 per cent of that in the ultra–centrifugated microsomes.

UDPGlucuronosyltransferase and Mixed Function Oxidase Activity in Microsomes Prepared by Differential Centrifugation and Calcium Aggregation

The effects of phenoxyacid herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and MCPA (4-chloro-2-methylphenoxyacetic acid), clofibrate, and glyphosate on hepatic and intestinal drug metabolizing enzyme activities were studied in rats intragastrically exposed for 2 weeks. The hepatic ethoxycoumarin O-deethylase activity increased about 2-fold with MCPA. Both 2,4-D and MCPA increased the hepatic epoxide hydrolase activity and decreased the hepatic glutathione S-transferase activity. MCPA also increased the intestinal activities of ethoxycoumarin O-deethylase and epoxide hydrolase. Glyphosate decreased the hepatic level of cytochrome P-450 and monooxygenase activities and the intestinal activity of aryl hydrocarbon hydroxylase. Clofibrate decreased the hepatic activities of UDPglucuronosyltransferase with p-nitrophenol or methylumbelliferone as the substrate. Also 2,4-D decreased the hepatic activity of UDPglucuronosyltransferase with p-nitrophenol as the substrate. MCPA decreased the intestinal activities of UDPglucuronosyltransferase with either p-nitrophenol or methylumbelliferone as the substrate. The results indicate that phenoxyacetic acids, especially MCPA, may have potent effects on the metabolism of xenobiotics. Glyphosate, not chemically related to phenoxyacids, seems to inhibit monooxygenases. Whether these changes are related to the toxicity of these xenobiotics remains to be clarified in further experiments.

Effects of phenoxyherbicides and glyphosate on the hepatic and intestinal biotransformation activities in the rat.

Action of styrene and its metabolites styrene oxide and styrene glycol on activities of xenobiotic biotransformation enzymes in rat liver in vivo

1. The rise in p-nitroanisole O-demethylase activity in liver microsomes after phenobarbital treatment of rats slightly preceded, and was greater than, the increase in hepatic microsomal UDP-glucuronyltransferase activity.2. Predigestion of hepatic microsomes with trypsin was necessary in order to detect the increase in UDP-glucuronyltransferase activity. Digitonin was not able to reveal the increase induced by phenobarbital.3. Trypsin digestion of hepatic microsomes solubilized about 30% of the proteins in control rats and 45% in microsomes isolated from phenobarbital-treated rats. The amount of solubilized phospholipids was only about 6% in both cases.4. The proteins solubilized by trypsin contained some components of the mixed-function oxidase including all of the NADPH cytochrome c reductase and a part of the cytochrome P-450 (as cytochrome P-420).5. The trypsin digestion appears to peel off the superficial proteins of the microsomal vesicle and to uncover UDP-glucuronyltransferase from the de...

Drug hydroxylation and glucuronidation in liver microsomes of phenobarbital-treated rats.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2872%2980363-6

Harri Vainio

Papers

UDPGlucuronosyltransferase and Mixed Function Oxidase Activity in Microsomes Prepared by Differential Centrifugation and Calcium Aggregation

Effects of phenoxyherbicides and glyphosate on the hepatic and intestinal biotransformation activities in the rat.

Action of styrene and its metabolites styrene oxide and styrene glycol on activities of xenobiotic biotransformation enzymes in rat liver in vivo

Drug hydroxylation and glucuronidation in liver microsomes of phenobarbital-treated rats.

Enhancement of drug oxidation and conjugation by carcinogens in different rat tissues