Ciclamato

Int. J. Morphol.,
23(3):221-226, 2005.

Effect of Sodium Cyclamate on the Rat Fetal Liver:
A Karyometric and Stereological Study
Efectos del Ciclamato de Sodio en el Hígado Fetal de Ratas:
Estudios Cariométrico y Estereológico
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Alex Tadeu Martins; *Reinaldo Azoubel; **Ruberval A. Lopes; **Miguel A. Sala di Matteo & *José Germano Ferraz de Arruda

MARTINS, A. T.; AZOUBEL, R.; LOPES,R. A.; DI MATTEO, M. A. S.; ARRUDA, J. G. F. Effect of sodium cyclamate on the rat
fetal liver: A karyometric and stereological study. Int. J. Morphol., 23(3):221-226, 2005.

SUMMARY: The cyclamate, a sweetner substance derived from N-cyclo-hexyl-sulfamic acid, is largely utilized as a non-caloric
artificial edulcorant in foods and beverages as well as in the pharmaceutical industry. Theobjective of this study was to evaluate fetal
hepatic karyometric and stereological alterations in the rat fetal liver resulting from the intraperitoneal administration of sodium cyclamate.
The livers of ten rats were evaluated, five treated and five controls chosen at random, in which five rats that received from the 10th to 14th
days of pregnancy an intraperitoneal daily injection of sodiumcyclamate at 60 mg/Kg of body weight during 5 days. At the 20th day of
gestation, the animals were removed and weighed, as were their placentas, on a precision balance; the length of the umbilical cords also
were measured. After the laboratory processing, semi-seriated 6mm cuts stained with haematoxyline and eosine were performed. In
seven karyometric parameters (major, minor, and medium diameters,volume, area, perimeter, and volume-area ratio), the increase was
statistically significant in the treated group when compared with control group. Stereological parameters showed in the treated group a
significant increase in the cytoplasmatic and cellular volume, and a significant reduction in the nucleus-cytoplasm ratio as well as in the
numerical cellular density. These results showed that thesodium cyclamate in pregnant rats led to retardation of fetal development and
hepatic-cellular hypertrophy in the offspring, suggesting toxicity in liver of rat fetuses.
KEY WORDS: Sodium cyclamate; Fetal liver; Karyometry; Stereology.

INTRODUCTION

Cyclamate, derived from N-cyclo-hexyl-sulfamic
acid (CHS), and amply utilized as a non-caloric artificial
edulcorant in foods and beveragesas well as in the
pharmaceutical industry. It is odorless and soluble in water,
alcohol and propylene glycol (Sain & Berman, 1984) and
more stable than aspartame and saccharine, and thus may
submitted to variations in temperature. (Barlattani, 1970).
Cyclamate was discovered in 1937 at the University
of Illinois, USA, by the graduate student Michael Sveda who
accidentally perceived itssweet taste, 30 times sweeter than
saccharine but without its bitter flavor (Audreith & Sveda,
1944). Beginning in 1959, the Food and Drug Administration
(FDA) added cyclamate to the list of safe substances, thus
permitting its use as a non-caloric artificial edulcorant for
diabetics. (Ahmed & Thomas, 1992).

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During the 1960s, the mixture of cyclamate and
saccharine in a 10:1proportion, drove an increase in the
consumption of this substance in the USA to a level
approaching 8.943 tons of cyclamate in 1969. (Burbank &
Fraumeni Jr., 1970).
In the following year, Price et al. (1970) evaluated
the development of tumors in the bladder of rats treated with
high doses of cyclamate, which was interpreted by the Food
and Drug Administration (FDA) as a substance that possiblyinduces cancer. Subsequent to this study, the U. S.
Department of Health, Education and Welfare (HEW)
concluded that cyclamate did not presented any value in the
treatment of obesity or diabetes (Egeberg et al., 1970) and
its utilization became prohibited in the USA, remaining so
to this day.

Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil....