Protective Effects Of Taurine Combined With DFP On Liver And Kidney Function And Antioxidant System In Rats Exposed To Aluminum

Aluminum（A1）is the most abundant metal element in the earth’s crust,which is widely found in water,air and soil.Due to its excellent physical and chemical properties,it has been widely used in food additives,water purification,food packaging materials,containers,utensils,etc.Which lead to an enormously increase on the exposure and intake of Al.The accumulation of A1 can cause toxic effects on many tissues and organs,liver is the major metabolic organ of Al,kidney is the main excretion organ of Al,thus it’s easier for Al to accumulate in these two organs.At present,there are a lot of research on the neurotoxicity of Al,but few research on hepatotoxicity and nephrotoxicity of Al.Taurine（Tau）has a wide range of biological functions,which has been proved to be able to alleviate the toxicity of some heavy metals.1,2-two methyl-3-hydroxy pyridine（DFP）is a kind of metal chelating agent,which can effectively remove aluminum.The study on the protection of taurine plus DFP on the function and antioxidation system of liver and kidney in Al-exposed rats was not reported.ObjectiveIn this study,Wistar rats were selected to establish a model of aluminum poisoning by administered with Aluminum Chloride Hexahydrate（AlCl3·6H2O）intragastrically and then treated with taurine and DFP alone and combined.Through the determination of activity of antioxidant enzymes,biochemical indexes,the essential elements and adenosine triphosphatase activity,to study the protective effects of taurine plus DFP on liver and kidney function and antioxidant system in rats exposed to aluminum.Methods1.Animal experiment56 male SPF Wistar rats（180-220g）were randomly divided into seven groups based on body weight with each group containing 8 rats.The control group received 1 mL/kg/day saline solution for 8 weeks.All intervention groups were given 281.40mg/kg AICl3 solution in exposure for the first 4 weeks.Then for the last 4 weeks,Al-exposed group was given 1.0ml/d saline,Tau group was given 400mg/kg Tau,low-dose DFP group was given 13.82mg/kg DFP,high-dose DFP group was given 27.44mg/kg DFP,Tau+low-dose DFP group and Tau+high-dose DFP were given 13.82,27.44 mg/kg DFP 6h right after Tau treatment,respectively.Rats were fasted for 24h after treatments before sacrificed,The blood was selected,the liver and kidney were quickly removed on ice and stored for the next biossays.2.Effects of taurine combined with DFP on liver function in rats exposed to aluminumThe rats were sacrificed to collect blood after static centrifugal serum,alanine aminotransferase（ALT）activity,aspartate aminotransferase（AST）activity,total bile acid（TBA）content were measured to explore the combined application of taurine and DFP on the recovery of liver function in rats exposed to aluminum3.Effects of taurine combined with DFP on renal function in rats exposed to aluminumThe rats were sacrificed to collect blood after static centrifugal serum,the content of serum creatinine（Scr）and blood urea nitrogen（BUN）were measured to explore the combined application of taurine and DFP on the recovery of renal function in rats exposed to aluminum.4.Effects of taurine combined with DFP on antioxidant system in liver and kidney of rats exposed to aluminumAfter the rats were sacrificed,liver and kidney were isolated and made into tissuehomogenate with normal saline.The MDA content,superoxide dismutase（SOD）activity,glutathione peroxidase（GSH-Px）activity and xanthine oxidase（XOD）activity were determined to explore the effects of taurine combined with DFP on antioxidant system in liver and kidney of rats exposed to aluminum.5.Effects of taurine and DFP on the activity of ATP in liver and kidney of rats exposed to aluminumAfter the rats were sacrificed,liver and kidney were isolated and made into tissue homogenate with normal saline.The Na⁺K⁺-ATP enzyme activity,Mg²⁺-ATP enzyme activity and Ca²⁺-ATP enzyme activity were determined to explore the antagonistic effect of taurine combined with DFP of aluminum-induced reduction of ATPase activities.6.Effects of taurine and DFP on the contents of essential elements in liver and kidney of rats exposed to aluminumAfter the rats were sacrificed,liver and kidney were isolated and made into tissue homogenate with normal saline.The content of iron,zinc,copper,calcium and magnesium were determined to explore the restoring effect of taurine combined with DFP on aluminum-induced function elements imbalance.Results1.Effects of taurine combined with DFP on liver function in rats exposed to aluminumThere is a significant increase in ALT and AST activities and TBA content in serum in Al-treated group compared with control group（P<0.05）.Compared with Al-treated group rats,ALT activity was significantly lower in all treatment group（P<0.05）.AST activity and TBA content were significantly lower in the high-dose deferiprone（DFP）,taurine（Tau）+low-dose DFP,Tau+high-dose DFP,and control groups compared with the Al-treated group（P<0.05）.Compared with the Tau and low-dose DFP group,ALT and AST activity and TBA content were significantly lower in Tau+low-dose DFP group（P<0.05）.Compared with the Tau group,ALT and AST activity and TBA content were significantly lower in Tau+high-dose DFP group（P<0.05）.2.Effects of taurine combined with DFP on renal function in rats exposed to aluminumThere was a significant increase BUN content in serum in Al-treated group compared with control group（P<0.05）.Compared with Al-treated group rats,BUN content was significantly lower in all treatment group（P<0.05）.Compared with the Tau and low-dose DFP group,BUN content were significantly lower in Tau+low-dose DFP group（P<0.05）.Compared with the Tau group,BUN content were significantly lower in Tau+high-dose DFP group（P<0.05）.There was no significant difference in serum Cr content between control group and all treatment group.3.Effects of taurine combined with DFP on antioxidant system in liver and kidney of rats exposed to aluminumThere were significantly higher MDA levels but lower SOD and GSH-Px activity in the liver and kidney in Al-treated compared with controls（P<0.05）.MDA contentwas significantly lower and GSH-Px was higher in all treatment groups and control group compared with the Al-treated group（P<0.05）.SOD activity in the high-dose DFP,Tau+low-dose DFP,and Tau+high-dose DFP groups were significantly higher than those in the Al-treated group（P<0.05）.Compared with the Tau and low-dose DFP groups,GSH-Px activity was significantly higher in the high-dose DFP,Tau+low-dose DFP,Tau+high-dose DFP group,and control groups（P<0.05）,while MDA was significantly lower（P<0.05）.There was no significant difference in GSH-Px activity and MDA content between Tau+high-dose DFP group and high-dose DFP group.There were no significant difference in SOD activity between the combined treatment group and separated medication group.There were no significant difference in XOD activity between all groups.4.Effects of taurine and DFP on the activity of ATP in liver and kidney of rats exposed to aluminumA1 significantly lowered Na⁺K⁺-ATPase and Mg²⁺-ATPase activity in liver and kidney compared with control group（P<0.05）.The activities of Na⁺K⁺-ATPase and Mg²⁺-ATPase were significantly higher in all treatment groups compared with the Al-treated group（P<0.05）.Compared with the Tau and low-dose DFP groups,the activity of Na⁺K⁺-ATPase and Mg²⁺-ATPase were significantly higher in Tau+low-dose DFP in kidney（P<0.05）.Compared with the Tau group,Na⁺K⁺-ATPase and Mg²⁺-ATPase were significantly higher in Tau+high-dose DFP group in kidney（P<0.05）.There was no significant difference in Na⁺K⁺-ATPase and Mg²⁺-ATPase activity between Tau+high-dose DFP group and high-dose DFP group in kidney.Compared with the Tau and low-dose DFP groups,the activity of Na⁺K⁺-ATPase were significantly higher in Tau+low-dose DFP and Tau+high-dose DFP group in liver,while there was no significant difference in Mg²⁺-ATPase activity.There were no significant difference in Ca²⁺-ATP activity between all groups.5.Effects of taurine and DFP on the contents of essential elements in liver and kidney of rats exposed to aluminumThere were significantly higher Cu（Copper）content,but lower Fe（Iron）content and Zn（Zinc）content in liver and kidney in Al-treated compared with controls（P<0.05）.Fe content was significantly higher in all treatment groups and control group compared with the Al-treated group（P<0.05）.Zn content in the high-dose DFP,Tau+low-dose DFP,and Tau+high-dose DFP groups were significantly higher than those in the Al-treated group（P<0.05）.Cu content in the high-dose DFP,Tau+low-dose DFP,andTau+high-dose DFP groups were significantly lower than those in the Al-treated group（P<0.05）.Compared with the Tau and low-dose DFP groups,Fe content and Zn content were significantly higher in Tau+low-dose DFP group（P<0.05）,while Cu content was significantly lower（P<0.05）.Compared with the Tau and low-dose DFP’ groups,Fe content and Zn content were significantly higher in Tau+high-dose DFP group（P<0.05）,while Cu content was significantly lower（P<0.05）.There were no significant difference in Cu,Fe,Zn content between high-dose DFP group and Tau+high-dose DFP group.There were no significant difference in Ca（Calcium）,Mg（Magnesium）content between all groups.Conclusions1.The combined application of Tau and DFP had a significant effect on the recovery of liver and kidney function in rats exposed to Al.2.The combined application of Tau and DFP could protect the antioxidant system of liver and kidney of rats exposed to Al.3.The combined application of Tau and DFP can effectively inhibit the reduction of activity of ATP enzyme in the liver and kidney of rats induced by Al.4.The combined application of Tau and DFP has a certain effect on the recovery of discord of iron,zinc,copper and other essential elements.5.Combined application of Tau and DFP resulted in a better protective effect compared with DFP or Tau alone.