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Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.

The contribution of adenosine receptors was evaluated in vascular relaxation in experimental hypothyroidism. Hypothyroid aortic rings contracted less than normal controls with noradrenaline, phenylephrine, and KCl; the difference was maintained after incubation with 1,3-dipropyl-8-p-sulfophenylxanthine (an A1 and A2 adenosine receptor blocker). The vascular relaxation induced by acetylcholine or carbachol was similar in normal and hypothyroid aortic rings. However, adenosine, N6-cyclopentyladenosine (an A1 adenosine receptor analogue), and 5'-N-ethylcarboxamidoadenosine (an A2 and A3 adenosine analogue) induced vasodilation that was larger in hypothyroid than in normal aortas. Nomega-nitro-L-arginine methyl ester shifted the dose-response curves of adenosine, N6-cyclopentyladenosine, or 5'-N-ethylcarboxamidoadenosine to the right in both normal and hypothyroid vessels. The blocker 1,3-dipropyl-8-p-sulfophenylxanthine significantly reduced adenosine-induced relaxation in the hypothyroid but not in the normal aortic vessels. These results suggest that in hypothyroid aortas, a larger adenosine-mediated vasodilation is observed probably due to an increase in receptor number or sensitivity.

We studied the effects of chronic arsenic exposure on brain monoamines and plasma levels of adrenocorticotropic hormone (ACTH) of mice. After weaning, mice received arsenic (0, 20, 40, 60 or 100 ppm) in drinking water over a period of 9 weeks. Monoamine content was quantified in different brain regions, arsenic was quantified in brain tissue and ACTH levels in plasma. Brain arsenic concentrations up to 200 ng/g showed a significant correlation with exposure levels and produced slight modifications in regional monoamine levels. ACTH plasma levels were significantly associated with norepinephrine (NE) concentrations in the medulla and pons, but not with hypothalamic NE levels. ACTH levels were significantly higher in the group exposed to 20 ppm. Dopamine showed significant dose-related decreases in the hypothalamus. These results show that chronic sodium arsenite exposure produces changes in central monoamines, which are not associated on a dose-dependent basis with major alterations in plasma ACTH.

In the hypothyroid kidney, exogenous adenosine (ADO) produces vasodilation and restores renal function to near-normal values. This study evaluates whether this response is mediated by nitric oxide synthesis stimulated by adenosine. GFR and urinary excretion of NO2-/NO3- (UNO2-/NO3-) were measured in normal (NL) and hypothyroid (HTX) rats under basal conditions and during infusion of: intra-aortic ADO, intravenously, 1,3-dipropyl-8p-sulfophenylxanthine (DPSPX), 8-cyclopentyl-1,3-dipropyl xanthine (DPCPX), N(omega)-nitro-L-arginine methylester (L-NAME) + ADO, L-NAME + PSPX, L-NAME + DPCPX, and intrarenal (IR) ADO or DPCPX + IR ADO. Intra-aortic ADO induced a fall in GFR and increased UNO2-/NO3- slightly in NL rats; in HTX rats, both GFR and UNO2-/NO3- increased significantly. DPSPX and DPCPX increased UNO2-/NO3- excretion in NL animals with minor changes in GFR; the blockers increased both GFR and UNO2-/ NO3- in HTX rats. L-NAME completely blocked the increase in NO2-/NO3- induced by ADO, DPSPX, and DPCPX. The intrarenal infusion of ADO at 1, 10, and 35 nmol/kg per min progressively decreased GFR with a slight increase in UNO2-/ NO3- in NL rats; in the HTX, GFR increased with the highest dose and UNO2-/NO3- progressively increased. DPCPX prevented the fall in GFR induced by intrarenal ADO in NL rats, with no further changes in UNO2-/NO3-; in HTX rats, intrarenal ADO under A1 blockade further increased GFR and UNO2-/NO3-. Arterial and venous ADO concentrations were lower in the HTX rats. In the HTX kidney, NO production was stimulated by ADO, most likely through activation of A2 or A3 receptors, whereas A1 receptors had an inhibitory effect. Thus, ADO receptors are involved in the regulation of kidney function in pathophysiologic conditions.