Effect Of High Molybdenum On The Toxic Effect And Damage Mechanism Of The Liver And Kidney In Sheep

Objective: As an essential trace element for organisms, molybdenum plays animportant role in growth and metabolism. Excessive intake of molybdenum can inducemolybdensis, which can impair the immune, urinary and gential functions. The studiesabout molybdensis mainly focused on the immune system and gential system, there arefew studies on the toxic effect of liver and kidney, especially in sheep.Methods: Three different doses of Molybdenum (Mo0mg/kg, groupⅠ; Mo30mg/kg, molybdenum group Ⅱ; Mo60mg/kg, molybdenum group III) were added tothe basal diets(Mo5.61mg/kg) for feeding of18sixty-days-old Small Tailed Han Sheepbeing divided into three groups randomly for120days. Autopsies were madeperiodically to get the blood and tissue specimens on the40th,80thand120th. Automaledhematologic analyzer was applied to detect the indexes of liver and kidney functions.Changes of the ultrastructure pathology of livers and kidneys were observed by themethod of transmission electron microscope. Activitives of antioxidant enzymes,contents of PCO and changes of nitrogen radicals were measured by means of chemicalchromatometry. The changes of tumor necrosis factor-alpha were measured by Enzymelinked immunosorbent assay. Flow cytometry was used to measure cell cycleparameters and apoptosis rates. To clarify the preliminary toxicity mechanism ofmolybdenum to livers and kidneys.Results:1. The liver functions indexes of glutamic-pyruvic transaminase andglutamic oxalacetic transaminase, and the kidney indexes of blood urea nitrogen andserum creatinine were higher when compared with those of the control. By TEM,mitochondria became swelling and degeneration were observed in groupⅡand III whencompared to that of the groupⅠ. The typical morphological changes of cells apoptosiswere observed included condensation and aggregation at the periphery of the nucleons.The kidney epithelial cells showed characeristic vacuolation, these were furtherevidence that the high molybdenum could damage the structure and functions of liversand kidneys in sheep. 2. Excessive intake of molybdenum induced the oxidative stress of the livers, decreasedthe activites of antioxidative enzymes, increased the activity of NOS and the contents ofNO and PCO, that could impair the antioxidative defense system of livers, decrease thescavenging activity of free radicals and lead to the oxidative damage, which is showedas time-and dose-dependent. The changes of these indexes in kidneys were inaccordance with the change in livers.3. Compared with groupⅠ, the expression of TNF-α was much higher than those of ingroupⅡ and III, the damage was being aggravated by the overexpression of TNF-α.4. By FCM, the results showed that the apoptosis rates of the livers and kidneys ingroup Ⅱ andIII were much higher when compared to group Ⅰ. Compared with groupⅠ, the cell cycle of hepatocyte was arrested in G0/G1phase in group Ⅱ and III, while,cell cycle of renal cells was arrested in S phase.Conclusion: The high molybdenum (>30mg/kg) impair the oxidative system, freeradicals metabolism, and genetic materials, which will have an adverse effect on thefunctions of livers and kidneys.