In vivo protective effect of melatonin on cadmium-induced changes in redox balance and gene expression in rat hypothalamus and anterior pituitary.
Cadmium (Cd) is widely used in industrial applications and is an important side contaminant of agricultural products. As an endocrine disruptor, Cd modifies pituitary hormone release. It has been shown that this metal causes oxidative stress in primary cultures of anterior pituitary cells. To examine whether Cd induces redox damage in the hypothalamic-pituitary axis in vivo and to evaluate the efficacy of the antioxidant molecule melatonin to prevent Cd activity, rats were exposed to Cd (5 p.p.m. in drinking water) with or without melatonin (3 microg/mL drinking water) for 1 month. In the anterior pituitary, Cd increased lipid peroxidation and mRNA levels for heme oxygenase-1 (HO-1) at both time intervals tested (09:00 and 01:00 hr, beginning of rest span and middle of activity span, respectively). Melatonin administration prevented the Cd-induced increase in both parameters. In the hypothalamus, Cd affected the levels of mRNA for HO-1 by decreasing it in the evening. Melatonin reduced hypothalamic HO-1 gene expression. Cd treatment augmented gene expression of nitric oxide synthase (NOS)1 and NOS2 in the pituitary whereas melatonin decreased it, impairing the activity of Cd. Exposure to Cd increased the levels of hypothalamic NOS1 mRNA at 09:00 hr and decreased the levels of NOS2 mRNA at 01:00 hr, with melatonin treatment preventing Cd effects. Cd treatment decreased plasma thyroid-stimulating hormone levels at both examined times, while melatonin reversed the effect of Cd at 09:00 hr and partially counteracted the effect at 01:00 hr. There were important variations between day and night in the expression of all the genes tested in both tissues. Melatonin treatment was effective reducing all examined effects of Cd, documenting its effectiveness to protect the rat hypothalamic-pituitary axis from the toxic metal effects.
Poliandri
Ariel H B
AH
Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Bueno Aires, Argentina.
Esquifino
Ana I
AI
Cano
Pilar
P
Jiménez
Vanessa
V
Lafuente
Anunciación
A
Cardinali
Daniel P
DP
Duvilanski
Beatriz H
BH
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002104:Cadmium; D008550:Melatonin