Dr. Sebastiano
Venturi
investigator on Iodine Deficiency Disorders
and Iodine metabolism
|
-Iodine in biology |
Dr. Sebastiano Venturi C.V. |
 |
"Iodide, thyroid and stomach carcinogenesis: evolutionary story of a primitive antioxidant?"
Sebastiano Venturi and Marta
Venturi
published in EUROPEAN JOURNAL OF ENDOCRINOLOGY. 1999,
140, Apr.4 :371-372
The thyroid gland is, embryogenetically
and phylogenetically, derived from primitive gut, and we may consider
the thyroid cells such as primitive gastroenteric cells which, during
evolution, migrated and specialized in uptake of iodide, and in storage
and elaboration of iodine compounds. Stomach and thyroid share iodine-concentranting
ability, and many morphological and functional similarities, such as cell
polarity and apical microvilli, similar organ-specific antigens and associated
autoimmune diseases (1), secretion of glycoproteins (thyroglobulin and
mucin) and peptide hormones, the digesting and readsorbing ability and,
lastly, similar ability to form iodotyrosines by peroxidase activity,
where iodide acts as electron donor in the presence of H2O2 (2). However,
gastric iodide-pump, phylogenetically more primitive than the thyroidal
one, has lower affinity for iodide and do not respond to more recent TSH.
So, in pregnant mouse, fetal gastric mucosa shows iodine-concentranting
ability earlier than fetal thyroid (3). During human total-body 131I-scintiscans,
the radioiodine remains on the stomach more than 72 hours. Similar finding
has been reported in bovine abomasum, since cows have an efficient iodine
recycling system via the gastrointestinal tract which conserves iodine
and can protect them against low dietary iodine (4). In primitive reptilian
stomach of lizard radioiodine remains more than 8 days (5). But which
is the role of iodide in the pathophysiology of the stomach? Dietary iodides
are able to defend brain cells from lipid peroxidation in rats (6). In
normal thyroid hormonogenesis iodide, giving its electron to oxygen, reduce
H2O2 by peroxidase activity. The remaining iodine readily iodinates the
tyrosine and so neutralizes its own high oxidant power. The antioxidant
action of iodide was described also in isolated rabbit eyes (7).
In old works, Stocks (8) and Spencer (9), reported
that iodine-deficient goitre constitute a risk for gastric cancer. Recently,
we reported (10) that iodine-deficiency (or excess) might represent a
risk factor for gastric cancer and atrophic gastritis, by regulating gastric
trophism and by antagonizing (in thyroid cells and in gastric mucosa)
the action of several iodine-inhibitors, such as nitrates, thiocyanates
and salt (11), which are well-known risk-factors for gastric carcinogenesis.
Furthermore, mammary gland has high ability to concentrate iodide and
to form iodoproteins by mammary peroxidase, exclusively during pregnancy
and lactation, which are considered protective conditions against breast
cancer (12). Recently, we have hypothesized that iodide might have, since
primitive Algae and primitive gastral cavity of Porifera, an antioxidant
role in iodine-concentranting organs, and particularly in the stomach
of the Vertebrates (13)(14). And now this role is experimentally confirmed
in Algae by a study carried out by F.C. Kupper et al.(15). In fact, three
billion years ago, Algae, which contain a high amount of iodine, were
the first living cells to produce oxygen, toxic at that time, in terrestrial
atmosphere. So, algae cells required a protective antioxidant action in
which iodides might have had a specific role. The thyroid gland is, phylogenetically
a modern organ and its function started and was improved from primitive
Chordates to more recent Mammalia. Also evolutionistically recent are
the T3-receptors in comparison with primitive Thyroxine (T4). In fact
T4 is present in fibrous exoskeletal tissues of the lowest animals (Invertebrates)without
showing any hormonal action (16). When the primitive marine-animals started
to emerge from the sea, rich of iodine, and transfered in iodine-deficient
mainland, their terrestrial diet became deficient of iodine and rich of
iodine-competitors (nitrates, nitrites, thiocyanates, some glycosides,
etc.). Therefore, we believe that, during the evolution to adapt to terrestrial
life, these animals learned to use the primitive T4, in the place of the
competitivized iodide, in order to transport into the cells this antioxidant
trace-element, utilizing the remaining T3, the real active hormone of
modern Vertebrates, for metamorphosis and thermogenesis with a new hormonal
action through the formation of T3-receptors (16). As inhibitors of lipid
peroxidation, by 5’-monodeiodinase activity, T4 and reverse T3 were found
to be more effective in this antioxidant activity than vitamin E, glutathione
and ascorbic acid (17).
In conclusion, we believe that the evolutionary story of
iodide and thyroid might suggest and explain a primitive antioxidant activity
of this trace-element. We should point out that extrathyroidal action
of iodide might be an important new area for investigation.
REFERENCES
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12) Eskin BA. Iodine metabolisme and breast cancer. NY Acad Sci 1970 32 911-947
13) Venturi S, Guidi A & Venturi M. I disordini extra-tiroidei da carenza iodica. Qual è il reale fabbisogno di iodio? Le Basi Razionali della Terapia 1996 16 267-75
14) Venturi S, Stanghellini V, Donati FM, Barbara B, Salvioli R & Corinaldesi R. Does dietary iodine prevent gastric cancer? Ital J Gastroenterol Hepatol 1998 30 238
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16) Venturi S. Letter to the Editor.The Thyroid Gland, Clinical and Experimental 1998 1 23
17) Tseng YL & Latham KR. Iodothyronines: oxidative deiodination by hemoglobin and inhibition of lipid peroxidation. Lipids 1984 19 96-102
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