Molecular and Cellular Endocrinology 319 (2010) 1–7
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Molecular and Cellular Endocrinology
journal homepage: www.elsevier.com/locate/mce
Ultrastructural and hormonal modulations of the thyroid gland following
arecoline treatment in albino mice
Romi Dasgupta
a
, Urmi Chatterji
a
, T.C. Nag
b
, Santasri Chaudhuri-Sengupta
a
,
Debabrata Nag
c
, B.R. Maiti
a,∗
a
Department of Zoology, University of Calcutta, Calcutta 700019, India
b
Department of Anatomy, AIIMS, New Delhi 110029, India
c
Department of Biochemistry, GIDSR, Calcutta 700140, India
article info
Article history:
Received 5 April 2009
Received in revised form 8 January 2010
Accepted 10 January 2010
Keywords:
Thyroid
Arecoline
Atropine
Mice
abstract
Arecoline is a plant alkaloid of betel nut Areca catechu. Arecoline has immunosuppressive, hepatotoxic,
mutagenic and teratogenic effects, and disturbs some endocrine organs in rats. The objective is to investi-
gate the untoward effects of arecoline on the thyroid gland in mice. Intraperitoneal injection of arecoline
(10 mg/kg body weight only once) increased the serum T
3
and T
4
levels and decreased the serum TSH 20,
40 or 60 min after the treatment, with maximum effect at 40 min. Chronic arecoline treatment (10 mg/kg
body weight daily for 15 days) caused light microscopic and ultrastructural degenerations of thyro-
follicular cells with depletion of T
3
and T
4
levels followed by the elevation of the TSH level. Atropine
(arecoline antagonist) injection prevented the changes (hyperactivity) induced by acute (40 min) arecline
treatment. Arecoline initially stimulates thyroid activity, and eventually inhibits the activity; atropine
prevents thyroid dysfunction induced by arecoline. Arecoline action is mediated probably via muscarinic
cholinergic receptor—hypothalamic–pituitary–thyroid axis in mice.
© 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Arecoline is a major plant alkaloid of betel nut Areca catechu
(Bhonsle et al., 1992). Millions of people of South East Asia, Indone-
sia and East Africa chew betel nut to increase the capacity to work
(Pradhan et al., 1986; Marshall, 1987). It has multiple actions in
humans and rats. It causes oral and throat cancer if taken 6 betel
nuts a day for long (Sullivan, 2000), genotoxicity (Sharan, 1996),
hepatotoxicity, disturbance in antioxidant production (Singh et al.,
2000), antibacterial activity (Huang et al., 2002), c-jun protoonco-
gene expression in human oral mucosal fibroblasts (Ho et al., 2000),
mutagenicity (Kumpawat et al., 2003), and teratogenesis leading to
abortion (Garcia-Algar et al., 2005). Arecoline arrests splenic lym-
phocytic cycle resulting in the immunosuppression and induces
hepatoxicity with depression of antioxidants in mice (Dasgupta et
al., 2006). Arecoline has some therapeutic value for the treatment of
patients with Alzheimer cum presenile dementia (memory enhanc-
ing effect) (Mondadore et al., 1994) and schizophrenia (Sullivan,
2000).
Arecoline also causes endocrine and brain dysfunctions. It
increases plasma concentration of beta-endorphin immunoreac-
tivity, which is correlated with the increase in plasma prolaction
∗
Corresponding author.
E-mail address: drbrm123@hotmail.com (B.R. Maiti).
concentration in humans (Risch et al., 1982). It stimulates adreno-
cortical and adrenomedullary activities in rats (Calogero et al.,
1989; Lim and Kim, 2006) and testosterone production (Saha et al.,
2007). But in mice arecoline has been reported to cause ultrastruc-
tural degeneration of adrenal cortex (unpublished observation).
Pineal activity is inhibited by arecoline in rats (Saha et al., 2007).
The importance of the current work is to ascertain the untoward
effects of arecoline on other endocrine organs, if any, that may be
relevant to those who consume betel nut almost daily throughout
life. There is no information concerning the action of arecoline on
the thyroid gland of vertebrate animals. Neither its mode of action
on endocrine organs isknown. In the current article, these problems
are resolved by investigating the light microscopic, ultrastructural
and hormonal changes of thyroid gland in the mouse model. The
mode of arecoline action was investigated by using muscarinic
receptor inhibitor, because arecoline is known to mediate its action
via muscarinic cholinergic receptor (Calogero et al., 1989).
2. Materials and methods
2.1. Animal model
Adult male mice (90 days, ∼25 g body weight) were collected from the breed-
ing colony and were kept in polythene cage (30 cm × 15 cm × 15 cm) in controlled
laboratory conditions (photoperiod, 12L: 12D, and temperature: 25
◦
C) with stan-
dard diet (Oser, 1965) and water accessible ad libidum 5 days for acclimatization
and subsequently for experiments.
0303-7207/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.mce.2010.01.005