#6057 REDUCTION OF SUBACUTE LEAD INDUCED PARATOHORMONE LEVELS FOLLOWING ANTIOXIDANTS OR VITAMIN D/CALCIUM ADMINISTRATION IN RATS

Abstract

Abstract Background and Aims Lead (Pb) is a toxic heavy metal; exposure is associated with many diseases. Accordingly, the World Health Organization considers Pb one of 10 chemicals of major public health concern. Experimental evidence suggests that Pb exposure induces both structural and functional kidney alterations. Epidemiological studies on lead exposed workers, show alteration on calcium metabolism (reduction in serum calcium, phosphorous and vitamin D and increase level of PTH) that increases with exposure length. Two of the suggested molecular mechanism of lead toxicity are: protein binding sites competition with endogenous cations such as calcium or zinc and the production of free radicals. The aim of this work is to analyze the effect of lead exposure, the therapeutic administration of antioxidants (melatonin or silymarin) or VitD +Ca and its potentially beneficial effect on calcium metabolism. Method Male Wistar rats (150–180 g body weight) of 6 weeks of age were housed in groups of three in standard cages with free access to water and food (Rodent Lab Standar Diet), under a 12/12 hour light/dark cycle, C, control: untreated rats not exposed to Pb or treatment; Pb, exposed to Pb for 1 month and assessed immediately; Pb 1NT, exposed to Pb for 1 month followed by 1 month without any treatment; Pb 1TM, exposed to Pb for 1 month followed by 1 month of melatonin treatment; Pb 1TS, exposed to Pb for 1 month followed by 1 month of silymarin treatment; Pb 1TVDCa, exposed to Pb for 1 month followed by 1 month of VitDCa treatment. M, melatonin (10 mg/kg/body weight/day dose), S silymarin (200 mg/kg/body weight/day dose) or total amount of VitD (232 IU/Kg/day) and Calcium 299 mg/Kg/day received from diet and therapeutic regimen were equal to 1.8 fold the daily requirement of VitD 800 IU/Kg/day and Calcium 1000 mg/Kg/day. Chemicals: Lead acetate trihydrate, Pb(CH3CO2)2.3H2O purity 99.99% from Sigma 215902, Melatonin Sigma M5250 98% TLC, VitaminD3 ampoules (100 000IU/mL), vitamin D oral ampoules (100 000IU/2 mL) from TRB Lab. Rat parathyroid PT Elisa Kit CUSABIO, 25-hydroxy Vitamin D3 ELISA Kit (Colorimetric) Kit NOVUS Results Blood Lead Levels There were statistical differences between the control group and all other groups P<0.0001. The group exposed to Pb for 1 month without any subsequent treatment (Pb 1NT) show differences in BLL with rats exposed to Pb and subsequently treated with antioxidant or VitD therapy and with the group immediately assessed after lead exposure. BLL were: all in μg/dL C 2.3, Pb 11, PbNT14.15, PbTM 10.28, PbTS 10.23 and Pb VDCa 10.18 Vitamin D Blood Levels Interestingly the highest mean vitamin D blood level was found in rats exposed to Pb for 1 month followed by 1 month of VitDCa therapy (Pb 1TVDCa) and the lowest mean value was found in rats exposed to Pb for 1 month and assessed immediately (Pb). PTH Blood Levels PTH blood levels were increased in rats exposed to Pb without any other treatment, whether assessed immediately after exposure or after one month. All therapies reduced blood PTH under control levels. Conversely a negative moderate correlation was found between blood levels of PTH vs. VitD r = −0.533 and r2 = 0.2843 P (two tailed) = 0.002. Conclusion All therapies using the antioxidants (melatonin or silymarin) or VitD+Ca supplementation reduced the lead induced increase in parathormone levels in rats.