Endocrine Abstracts

Objectives: Chromium (Cr) is one of the major and most detrimental heavy metal pollutant. It is classified as an endocrine disrupting chemical (EDC, endocrine disruptor) and possibly thyroid disruptor. Its main forms are hexavalent (Cr(VI)) and trivalent chromium (Cr(III)). In turn, Cr is also classified as a carcinogen, with Cr(VI) belonging to group 1 of carcinogens (carcinogenic to humans) according to the International Agency for Research on Cancer (IARC) Monographs. Although Cr(III) is recognized by IARC as group 3 agent (not classifiable as to its carcinogenicity to humans), the carcinogenic activity of Cr is thought to be due to macromolecular damage caused by reactive intermediates arising in the course of its intracellular reduction to Cr(III). The study aimed to check if and to what extent melatonin and other known antioxidants, such as indole-3-propionic acid (IPA) and 17β-estradiol, may prevent oxidative damage to membrane lipids (lipid peroxidation, LPO) caused by Cr(VI) compound, i.e., potassium dichromate (VI) (K₂Cr₂O₇), as well as by Cr(III) compound, i.e., chromium (III) chloride hexahydrate (CrCl₃ • 6 H₂O), in homogenates of two endocrine tissues, such as the thyroid and the ovary, and of two non-endocrine tissues, such as the liver and the kidney. Of note, the thyroid gland is characterized by relatively high oxidative stress.

Methods: Porcine tissue homogenates were incubated in the presence of tested Cr compounds, i.e., potassium dichromate (VI) (K₂Cr₂O₇) in concentrations of 0.05-10.0 mM, or chromium (III) chloride hexahydrate (CrCl₃ • 6 H₂O) in concentrations of 5.0-200.0 mM, with/without melatonin (5 mM) or IPA (5 mM) or 17β-estradiol (1 mM). The malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) concentration (LPO index) was measured spectrophotometrically.

Results: Both Cr compounds caused huge concentration-dependent increase in LPO in all examined tissues. Cr(VI) compound, in concentrations of 0.1-1.25 mM or higher, significantly increased LPO in all examined tissues, but these damaging effects were not prevented by either melatonin or other antioxidants. In turn, Cr(III) compound, in concentrations of 25 mM or higher, also significantly increased LPO in all examined tissues. Neither melatonin nor other two antioxidants prevented these damaging effects of Cr(III) compound in the thyroid. However, all the antioxidants decreased Cr(III)-induced LPO in the ovary and in the kidney and, to a lower extent, in the liver.

Conclusions: Whereas melatonin exerts protective effects against Cr(III)-induced oxidative damage in the ovary, in the kidney, and in the liver, the thyroid does not respond to the antioxidative action of this indoleamine, which can be due to oxidative nature of the thyroid and relatively high level of oxidative damage in this endocrine gland observed even under physiological conditions. Neither melatonin nor other antioxidants are able to reveal protective effects against Cr(VI)-induced oxidative damage in the thyroid as well as in other examined tissues.