Effect of Acrylamide on Stomach, Cerebellum and Testis of the Albino Rat

THESIS Submitted for the Partial Fulfillment of the

M.D. Degree in Anatomy

Presented by

Hesham Noaman Abdel Raheem Mustafa M.B., B.Ch. & M.Sc. of Anatomy

Assistant lecturer of the Anatomy

Supervised by

Professor Dr. Kariman Mohammed El-Gohari Professor of Anatomy

Head of Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University

Professor Dr. Ezz El-Deen Helmy Helaeil Professor of Anatomy

Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University

Dr. Hassan Mostafa Serry Assistant Professor of Anatomy

Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University

Dr. Shahira Samir Zaki Assistant Professor of Anatomy

Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University

Faculty of Medicine Ain Shams University

2005

Introduction

Acrylamide is a white, odorless chemical substance

(C3H5NO) with MW (71.08), used in Mining industry and in

Water treatment (Murray and Seger, 1994).

Recently, it has been reported that acrylamide monomer

may form in certain foods cooked at high temperatures, the

highest concentrations of acrylamide have been identified in

potato chips, French fries and grain-based foods that are cooked at

very high temperatures during frying, grilling or baking (Tareke

et al. 2002). In that respect, the German Federal Institute for Risk

Assessment stated in a December 10, 2002, press release that the

acrylamide content rises suddenly in French fries, from

approximately 300 micrograms per kilogram at 175 degrees

Celsius (347 degrees Fahrenheit) to 1,100 micrograms per

kilogram at 180 degrees Celsius (356 degrees Fahrenheit).

Acrylamide is thought to form in food principally from the

interaction of the amino acid asparagines with glucose or other

carbohydrates (Bachmann et al. 1992).

Acrylamide is thought to produce cancer in animals and

its presence in some foods may harm peoples health. Moreover,

at low levels, acrylamide is a potent neurotoxin affecting both

central and peripheral nervous systems (DeRojas and Goldstein,

1987). Chronic oral exposure to acrylamide in humans has

resulted in nerve damage accompanied by weakness and

numbness in the extremities. Moreover, the acute inhalation of

acrylamide may cause central and peripheral nervous system

damage resulting in symptoms ranging from drowsiness to

hallucinations. In addition, the chronic dermal exposure to

acrylamide may cause a rash (U.S. EPA, 1994). In addition,

acrylamide affects the reproductive function in rats, as it appears

to cause testicular atrophy and produces both a decreased sperm

count and an increase in abnormal sperm morphology (Sakamoto,

J. and Hashimoto, K. 1986). Moreover, hepatoxicity is reported

following acute ingestion of acrylamide (Donovan and Pearson,

1987; Shelly, 1996). In addition, transient impairment in renal

function has been reported following acute ingestion (Shelly,

1996).

Using chronic dosing schedules, it has been observed that

cumulative oral doses of 500-600 mg/kg using daily doses of 25-

50 mg/kg/day are required to produce ataxia in rats, dogs and

baboons (McCollister et al., 1964; Hopkins, 1970; Thomann et

al., 1974). Smaller daily doses do not produce a clinical effect

until a larger cumulative dose is attained; Fullerton and Barnes

(1966) observed that administration of acrylamide at daily doses

of 6 to 9 mg/kg did not produce evidence of neurotoxicity in rats

until a cumulative dose of 1200 to 1800 mg/kg was attained.

Aim of the Study:

The present study aims at exploring the harmful effects of

acrylamide on the structure of the stomach, cerebellum and testis

in the albino rat, in an attempt to clarify its potential risk on the

human health.

Material and Methods: Thirty adult male albino rats will be divided into two

main groups. Group I will receive parentral acrylamide while

Group II will receive oral acrylamide in the drinking water. Each

group will be subdivided into three subgroups, 5 animals each, as

follows:

A- The parental Group I:

Subgroup 1, the controls, will be injected with intraperitoneal

saline.

Subgroup 2, will receive intraperitoneal injections of

acrylamide in a dose of 5 mg/kg.

Subgroup 3 will receive intraperitoneal injections of

acrylamide in a dose of 1000 mg/kg.

All animals will be injected once daily for 10 successive days.

B- The oral Group II:

Subgroup 1, the controls, will receive fresh water.

Subgroup 2, will receive 5 mg/kg body weight orally.

Subgroup 3, will receive 1000 mg/kg body weight orally.

All animals will be subjected to this regimen for 10 successive

days.

The animals will be sacrificed at the end of the treatment

period and specimens of stomach, cerebellum and testis will be

processed for histological study.

The procedure will be held at the Anatomy Department Faculty

of Medicine Ain Shams University.

References:

1) Bachmann, M., Myers, J. and Bezuidenhout, B. (1992):

"Acrylamide monomer and peripheral neuropathy in

chemical workers." Am. J. Ind. Med 21(2): 217-222.

2) Donovan, J.W. and Pearson, T. (1987): Ingestion of

acrylamide with severe encephalopathy, neurotoxicity and

hepatotoxcity. Vet Hum Toxicol, 29: 462.

3) DeRojas, T.C. and Goldstein, B.D. (1987): "Primary

afferent terminal function following acrylamide: alterations

in the dorsal root potential and reflex." Tox Appl Pharmacol

88: 175-182.

4) Fullerton, P.M. and Barnes, J.M. (1966): Peripheral

neuropathy in rats produced by acrylamide. Brit J Industr

Med, 23: 210-221.

5) Hopkins, A.P. (1970): The effect of acrylamide on the

peripheral nervous system of the baboon. J Neurol

Neurosurg Psychiatr, 33:805-816.

6) McCollister, D., Oyen, F. and Rowe, V. (1964):

"Toxicology of acrylamide." Toxicol. Appl. Pharmacol 6:

172-181.

7) Murray, L.M. and Seger, D.L. (1994): Acrylamide

neurotoxicity following occupation inhalation exposure. XVI

International Congress of the European Association of

Poison Centres and Clinical Toxicologists, Vienna, Austria.

8) Sakamoto, J., Hashimoto, K. (1986): Reproductive toxicity

of acrylamide and related compounds in mice-effects on

fertility and sperm morphology. Arch Toxicol; 59(4):201-5.

9) Shelly, (1996): Regina vs. Calder. In: Transcript records of

New Zealand High Court, Christchurch, New Zealand,

March 1996.

10) Tareke, E., Rydberg, P., Karlsson, P., Eriksson, S. and

Tornqvist, M. (2002): Analysis of acrylamide, a carcinogen

formed in heated foodstuffs. J. Agric. Food Chem. 50:4998-

5006.

11) Thomann, P., Koella, W.P., Krinke, G., Peterman, H.,

Zak, G. and Hess, R. (1974): The assessment of peripheral

neurotoxicity in dogs: Comparative studies with acrylamide

and clioquinol. Agent Actions, 4:47-53.

12) U.S. Environmental Protection Agency (1994): Drinking

Water Regulations and Health Advisories. Office of

Drinking Water, U.S. Environmental Protection Agency,

Washington, D.C.

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Effect of Acrylamide on Stomach, Cerebellum and Testis of the Albino Rat