Danijela Djukic-Cosic

Fluoride in drinking water and dental fluorosis.

In this study we determined the fluoride content in drinking water and hair of 12-year-old schoolchildren from different Serbian municipalities, i.e. Valjevo, Veliko Gradiste, Kacarevo and Vranjska Banja. The analyses were performed using composite fluoride ion-selective electrode. Average fluoride levels were 0.10, 0.15, 0.79 and 11 ppm in well water, 0.07, 0.10, 0.17 and 0.15 ppm in tap water, 19.3, 21.5, 25.4, and 32.5 ppm in hair samples, in Valjevo, Veliko Gradiste, Kacarevo and Vranjska Banja, respectively. Correlation analysis indicated statistically significant positive relationship between fluoride in wells water and fluoride in hair, for all municipalities: correlation coefficients were 0.54 (p < 0.05), 0.89, 0.97 and 0.99 (p < 0.001), in Vranjska Banja, Valjevo, Veliko Gradiste, and Kacarevo, respectively. Positive correlation was obtained also between fluoride in tap water and hair samples in all regions under the study, with statistical significance only in Valjevo municipality, p < 0.05. Dental examination of schoolchildren confirmed dental fluorosis only in the region of Vranjska Banja. Moreover, in endemic fluorotic region of Vranjska Banja, positive and statistically significant correlations were confirmed between fluoride in well water and dental fluorosis level (r = 0.61; p < 0.01) and additionally between fluoride in hair and dental fluorosis level (0.62; p < 0.01). The primary findings from this study have shown that fluoride content in hair is highly correlated with fluoride content in drinking water and dental fluorosis level, indicating that hair may be regarded as biomaterial of high informative potential in evaluating prolonged exposure to fluorides and to individuate children at risk of fluorosis regardless of the phase of teeth eruption.

Relation between lipid peroxidation and iron concentration in mouse liver after acute and subacute cadmium intoxication

In this study the effect of acute and subacute cadmium (Cd) intoxication on iron (Fe) concentration and lipid peroxidation (LPO) was investigated in the livers of Swiss mice. Animals were divided into two groups: the Cd group--mice intoxicated with Cd and controls. In acute time-response studies, Fe and malondialdehyde (MDA) levels were determined at 4, 6, 12, 24 and 48 h after a single oral dose of Cd (20 mg Cd/kg b.w.). In the subacute experiment, mice were given 10 mg Cd/kg b.w. orally every day for 14 days; Fe and MDA contents were determined in liver after 1 and 2 weeks. Acute Cd intoxication induced a significantly increased hepatic Fe content after 4 and 6h, and a statistically significant increase in MDA 6, 12 and 24h after Cd administration, although a significantly decreased MDA level was observed after 48 h. The results suggest development of early oxidative stress in livers of mice after acute intoxication with Cd. The decreased MDA observed after 48 h occurred presumably due to the adaptive response of the organism. Subacute Cd intoxication induced a significant decrease of hepatic Fe and MDA levels at both investigated time intervals compared with control. These results indicate a positive correlation between hepatic Fe and MDA content and suggest that prolonged Cd intoxication decreases hepatic LPO indirectly, by reducing the Fe content of mouse liver.

Antagonism between cadmium and magnesium: a possible role of magnesium in therapy of cadmium intoxication

One of the important mechanisms of cadmium (Cd) toxicity is its interactions with bioelements, including magnesium (Mg). Exposure to Cd leads to disturbances in Mg metabolism in the organism, while Mg supplementation has an adverse effect on Cd absorption, accumulation and toxicity. According to the available results, which indicate a protective role of Mg against Cd toxicity, it remains to be seen whether magnesium may influence the important unsolved problem of Cd intoxication therapy. In this review, the interactions between the toxic metal Cd and the bioelement Mg are discussed on the basis of the available literature and our own results. We discuss these interactions mainly based on experimental data because data from human studies are scarce.

Effect of supplemental magnesium on the kidney levels of cadmium, zinc, and copper of mice exposed to toxic levels of cadmium.

In this report, we present the results of our investigations on the effect of Mg pretreatment on Cd and bioelements (Cu and Zn) contents in kidney of mice exposed to acute and subacute Cd intoxication. Acute intoxication was performed on male Swiss mice given a single oral dose of 20 mg Cd/kg body weight and mice given the same dose of Cd but pretreated with 40 mg Mg/kg body weight. For subacute intoxication one group of mice was given 10 mg Cd/kg body weight every day, for 2 wk, and the other one received the same dose of Cd after oral Mg intake of 20 mg/kg body weight. Cd, Cu, and Zn content was determined in kidney by atomic absorption spectrophotometry. In acute Cd intoxication, Mg pretreatment resulted in significant decrease of Cd in kidney after 4 and 6 h, compared with animals given only Cd. Under the condition of subacute Cd intoxication, Mg supplementation reduced Cd kidney content after 2 wk for about 30%, compared with animals treated with Cd only. The effect of Mg on Cu and Zn kidney content was also beneficial.

Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor.

As oxime-based structures are the only causal antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE), the majority of studies on these have been directed towards their synthesis and testing. In this study, experimental bispyridinium oximes K027 and K203, which have shown promising results in the last decade of research, were examined in vivo for their therapeutic and reactivating ability in acute poisoning by the direct AChE-inhibitor dichlorvos (DDVP), used as a dimethyl OP structural model. Additionally, the efficacy of oximes K027 and K203 was compared with the efficacy of four oximes (pralidoxime, trimedoxime, obidoxime and HI-6), already used in efficacy experiments and human medicine. To evaluate therapeutic efficacy, groups of Wistar rats were treated with equitoxic doses of oximes (5% LD50, i.m.) and/or atropine (10mg/kg, i.m.) immediately after s.c. DDVP challenge (4-6 doses). Using the same antidotal protocol, AChE activity was measured in erythrocytes, diaphragm and brain 60min after s.c. DDVP exposure (75% LD50). The oxime K027 was the most efficacious in reducing the DDVP induced lethal effect in rats, while the oxime K203 was more efficacious than trimedoxime, pralidoxime and HI-6. Significant reactivation of DDVP inhibited AChE was achieved only with oxime K027 or its combination with atropine in erythocytes and the diaphragm. Moreover, the acute i.m. toxicity of oxime K027 in rats was lower than all other tested oximes. The results of this study support previous studies considering the oxime K027 as a promising experimental oxime structure for further testing against structurally-different OP compounds.

Dose-response modeling of reactivating potency of oximes K027 and K203 against a direct acetylcholinesterase inhibitor in rat erythrocytes

Inhibition of acethylcholinesterase (AChE) as a key molecular event induced by organophosphate (OP) pesticides and nerve agents presents a human health concern. In efficacy testing of experimental oximes, potential antidotes in OP poisoning, reactivation of OP-inhibited AChE is used as specific endpoint. However, according to our best knowledge, so far oximes have not been quantitatively evaluated by comprehensive benchmark dose (BMD) approach, that would improve both identification and quantification of the effect and allow more rigorous comparison of efficacies. Thus, we have examined in vivo dose-response relationship for two promising experimental oximes, K203 and K027, concerning reactivation of erythrocyte AChE inhibited by dichlorvos (DDVP). Groups of Wistar rats were treated with six different doses of oximes (i.m) immediately after DDVP challenge (s.c) and AChE was measured 60 min later. Dose-response modeling was done by PROAST software 65.5 (RIVM, The Nederlands). BMD-covariate method resulted in four-parameter model from both exponential and Hill model families as the best estimate of relationship between AChE activity and oxime dose, with potency parameter being oxime-dependent. Oxime K027 was shown to be 1.929-fold more potent considering that 58% increase in AChE activity was achived with the dose BMD58-K027 = 52 μmol/kg in contrast to BMD58-K203 = 100 μmol/kg.