Research Proposal: Chemical Substances on Liver

Pages: 10 (2880 words)  ·  Bibliography Sources: 30  ·  Level: Doctorate  ·  Topic: Medical and Medicine  ·  Buy This Paper

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[. . .] " The implications of pesticide exposure on the American public are significant. For example, Blindauer and Jackson (1999, p. 12) emphasize that, "More than one billion pounds of conventional pesticide active ingredients are used annually in this country. If wood preservatives and disinfectants are included, more than four billion pounds of pesticides are used annually."

As a result, it is reasonable to suggest that practically everyone in the United States is routinely exposed to some level of environmental pesticides (Blindauer & Jackson 1999). For instance, Blindauer and Jackson (1999, p. 12) note that, "The general public is frequently exposed to pesticide residues in food, as a consequence of agricultural applications to crops, as well as in water." Other sources of pesticide exposure that have the potential to adversely affect the general American population include regular applications of pesticides to yards and the pesticides that are blown on the wind from agricultural and forestry activities (Blindauer & Jackson 1999). In addition, the U.S. Environmental Protection Agency estimates that fully 85% of all American households contain stores of pesticides (Blindauer & Jackson 1999). Taken together, it is clear that there is a solid body of evidence that a wide range of substances in the environment can harm human kidneys and livers, but there are some gaps in this body of knowledge as discussed below.

Interlocking findings and unanswered questions

The human body is "hard-wired" to detoxify itself automatically through liver and kidney metabolic processes (Cavendish 2006), but a wide range of natural and artificial substances can overpower these organs' abilities to efficiently process toxins (Steenland & Fletcher 2010) and in some cases destroy them outright (Nyerges 2002). There remains a gap in the existing body of knowledge, though, concerning optimal practices for experimenting with laboratory rats and mice as discussed further in expected results further below.

Your preliminary work on the topic

To date, a preliminary review of the relevant peer-reviewed and scholarly literature concerning the toxic effects of various substances of liver and kidney enzymes and tissues has been conducted and a tentative budget developed in support of the related experiment described herein.

The remaining questions and inter-locking logic

Human experimentation is fraught with challenges and constraints, including inordinately high costs and ethical concerns. Therefore, researchers frequently use other mammals for experimentation, especially laboratory rats and mice (Donnelly 1989). Research with rats and mice has produced a number of valuable outcomes for human medicine (Krantz & Baum 1999). According to the Institutional Animal Care and Use Committee ('The laboratory rat' 2014, p. 3), "Like the mouse, the rat has many advantages as a research animal. The laboratory rat is readily available, is inexpensive, and easy to house. The genetic uniformity of available strains and stocks makes for reproducible research results." In addition, rats and mice animals are easily handled and these mammals have been used in studies of metabolism, physiology, nephrology, endocrinology, nutrition, drug evaluation and toxicology, as well as transplantable tumors ('The laboratory rat' 2014).

Reprise of your research question(s) in this context

A reprisal of the original research question in the revised context would be, "How can the acute or subacute biochemical and tissue changes that are produced by selected presumed nongenotoxic rodent carcinogens serve as predictors of nongenotoxic rodent carcinogenesis?"

Methodology

The proposed study will follow the methodology used by Elcombe and Odum (2002) to evaluate the ability of nine presumed nongenotoxic rodent carcinogens to induce acute or subacute biochemical and tissue changes in laboratory rats and mice which can serve as valuable predictors of nongenotoxic rodent carcinogenesis.

Approach

Nine presumed nongenotoxic rodent carcinogens, as defined by the U.S. National Toxicology Program (NTP), diethylhexyl phthalate, cinnamyl anthranilate, chlorendic acid, 1,4-dichlorobenzene, monuron, ethylene thiourea, diethyl thiourea, trimethyl thiourea, and d-limonene) will be administered to strains of mice and rats (nine chemicals to rats and seven to mice) following the guidelines used by Elcombe and Odum (2002) to evaluate these chemicals' ability to induce acute or subacute biochemical and tissue changes which can serve as valuable predictors of nongenotoxic rodent carcinogenesis.

Data needs

Selected tissues (liver and kidney) will be collected from the strains of rats and mice at 7, 28, and 90 days for evaluation purposes following the guidelines used by Elcombe and Odum (2002).

Analytic techniques

The tissue changes that will be selected for study will be evaluated for all of the test groups, irrespective of the specificity of the carcinogenic responses observed in those tissues. This approach provides the ability for the researchers to evaluate the carcinogen specificity as well as the carcinogen sensitivity of the monitored events (Elcombe & Odum 2002). The relative weight, cell labeling indices, and pathologic changes such as hypertrophy in all tissues will be analyzed following the procedures used by Elcombe and Odum (2002). In addition, a range of cytochrome P450 enzymes and palmitoyl coenzyme will be studied as well as oxidase in the liver; further, changes in the levels of plasma total triiodothyronine, total thyroxine, and thyroid-stimulating hormone (TSH) as markers of thyroid gland function; and hyaline droplet formation, tubular basophilia, and the formation of granular casts in the kidney will be analyzed (Elcombe & Odum 2002, p. 364).

Plan for interpreting results

Each of the nine chemicals, diethylhexyl phthalate, cinnamyl anthranilate, chlorendic acid, 1,4-dichlorobenzene, monuron, ethylene thiourea, diethyl thiourea, trimethyl thiourea, and d-limonene), will be evaluated to determine their respective ability to induce acute or subacute biochemical and tissue changes which can serve as valuable predictors of nongenotoxic rodent carcinogenesis.

Expected results

The outcome of this experiment is expected to mirror the results obtained by Elcombe and Odum (2002) with the addition of the identification of an optimal choice of markers and evaluation points. The results obtained by Elcombe and Odum showed that the chemical induction of cancer in a tissue was preceded by a range of biochemical/morphologic changes in the majority of cases; of these, the majority were also moderately specific for a carcinogenic outcome and in some cases, they were highly specific. According to Elcombe and Odum (2002, p. 364), "The only measurements that failed to correlate usefully with carcinogenicity were the induction of liver enzymes (with the exception of the enzymes associated with peroxisome proliferation)."

The majority of the markers that were deemed useful predictors were identified at the 7- and 28-day evaluation point; however, these researchers emphasize that they did not identify an overall optimal time for the measurement or the optimal choice of markers (Elcome & Odum 2002), a gap that in the body of knowledge that this experiment intends to fill.

Budget

Nine rats ($5.00/each)

$45.00

Seven mice ($3.00/each)

$21.00

Rodent food

$7.50

Rodent cages (16 x $8)

$128

Total

$201.50

References

Blindauer, KM & Jackson, RJ (1999, June), 'Environmental Pesticide Illness and Injury: The

Need for a National Surveillance System,' Journal of Environmental Health, vol. 61, no.

10, pp. 9-11.

Bryant, B (1999), Race and the Incidence of Environmental Hazards: A Time for Discourse.

Boulder, CO: Westview Press.

Cavendish, M (2006), Drugs and Society. New York: Marshall Cavendish Reference.

Donnelley, S (1989, March-April), 'Speculative Philosophy, the Troubled Middle, and Ethics of Animal Experimentation,' The Hastings Center Report, vol. 19, no. 2, pp. 15-19.

Elcombe, CR & Odum, J (2002, April), 'Prediction of Rodent Nongenotoxic Carcinogenesis:

Evaluation of Biochemical and Tissue Changes in Rodents Following Exposure to Nine

Nongenotoxic NTP Carcinogens,' Environmental Health Perspectives, vol. 110, no. 4,

pp. 363-370.

Elkhalifa, AA & Khateim, IE (2007, December), 'The Effect of Addition of Whey on the Acceptability of Tebeldi Juice,' Ahfad Journal, vol. 24, no. 2, pp. 123-129.

Ezendam, J & Staedtler, F (2004, May 15), 'Toxicogenomics of Subchronic Hexachlorobenzene

Exposure in Brown Norway Rats,' Environmental Health Perspectives, vol. 112, no. 7,

pp. 782-790.

Gorman, G (2002, Fall), 'Inside the Liver -- the Body's Refinery,' Nutrition Health Review, pp. 2-

3.

Krantz, DS & Baum, A (1999), Technology and Methods in Behavioral Medicine. Mahwah, NJ:

Lawrence Erlbaum Associates.

Maher, JJ (1997, January 1), 'Exploring Alcohol's Effects on Liver Function,' Alcohol Health & Research World, vol. 21, no. 1, pp. 5-10.

Marsano, LS & Mendez, C (2003, July 1), 'Diagnosis and Treatment of Alcoholic Liver Disease

and Its Complications,' Alcohol Research, vol. 27, no. 3, pp. 247-253.

Mottram, DR (2003), Drugs in Sport. London: Routledge.

Nyerges, C (2002,… [END OF PREVIEW]

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