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The Protective Effects Of Curcumin On Mitochondrial Oxidant Damages In Animals And The Potential Antioxidant Mechanism

Posted on:2016-02-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:J F ZhangFull Text:PDF
GTID:1313330512971024Subject:Animal Nutrition and Feed Science
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Curcumin is a fat-soluble pigment with the natural origin and appears brilliantyellow-orang hue.Curcumin is traditionally used as spice and pigment in the foodprocessing industry.In the last few years,curcumin has drawn a lot of attention inprevention and treatment of many diseases in clinic due to its strong free radical scavengingactivity and antioxidant capacity.The increasing demand for the safety of food and animalproduct have resulted in a trend towards "natural additives",including curcumin as anatural antioxidant in animal production.However,there is little information about theantioxidant effects of curcumin in animals and its possible mechanism of this action needfurther investigation.In the present study,these experiments were conducted,firstly,to compare theantioxidant activities of curcumin and other six natural pigments by the chemical assaysand the chicken erythrocyte model;secondly,to investigate the protective effects ofcurcumin against d-GalN/LPS-induced acute liver injury in mice and compare thediscrepancy between the pre-and post-treatment of curcumin;thirdly,to evaluate thevarying levels of curcumin on the growth performance,meat quality and antioxidant profileof the breast muscle in broiler;and eventually to explore the positive effects of curcumin onthe growth performance and hepatic oxidant damages under chronic heat stress through amitochondria]pathway.1 Assessment of free radicals scavenging activity of seven naturalpigments and protective effects in AAPH-challenged chickenerythrocytesThe aim of the present study was to investigate the antioxidant capacities of sevennatural pigments,which were first measured by chemical assays and then verified by thechicken erythrocyte model.The fat-soluble curcumin,lycopene,lutein and β-carotene andwater-soluble betalain,capsanthin and cyanidin-3-rutinoside were employed in thechemical assays.The antioxidant capacities of these seven pigments were evaluated basedon their ability to quench several free radicals,including DPPH·,ABTS·+,O2·-,H2O2 aswell as using FRAP assay.BHA,a commonly-used synthetic food antioxidant,were used asa reference standard.The results showed that these seven pigments exhibited strongactivities by quenching the free radicals.Specifically,curcumin and cyanidin-3-rutinoside,which showed the highest antioxidant capacities,were selected to investigate the protectiveeffects against AAPH induced-oxidative damage in chicken erythrocytes.It was found thatboth curcumin and cyanidin-3-rutinoside at the applied concentrations significantlyattenuated apoptosis and hemolysis,decreased MDA content,and increased T-SOD activityin a time-and dose-dependent manner.Compared to cyanidin-3-rutinoside,curcuminshowed more beneficial effects in AAPH-stressed chicken erythrocytes.In conclusion,ourresults demonstrated that the seven selected natural pigments showed varying extent inantioxidant activities in vitro,and suggested that the fat-soluble curcumin and thewater-soluble cyanidin-3-rutinoside were proven to be strong free radical quenchers andcapable to ameliorate the oxidant damages induced by AAPH.This work also laid thefoundation for the use of these natural pigments as alternative to synthetic antioxidants inthe food and feed industry.2 Curcumin attenuates d-GalN/LPS-induced liver injury andmitochondrial dysfunction in miceThe present study was aimed to investigate the protective effects of curcumin againstd-GalN/LPS-induced acute liver injury in mice.A total of 40 male Kunming mice wererandomly assigned into five groups:CON,CUR,GL,CUR-GL and GL-CUR groups.Twenty hours after d-GalN/LPS injection,mice were anesthetized for serum and hepaticsamples.Serum ALT and AST activities in the CUR-GL and GL-CUR groups weredecreased(P<0.05)as compared to the GL-CUR group.Compared to the GL-CUR group,the CUR-GL group had a 18.7%lower serum AST activity(P<0.05).Curcumin decreased(P<0.05)the mitochondrial MDA levels by 68.5%and 53.9%in the CUR-GL and GL-CUR groups,respectively,in comparison with the GL group.The CUR-GL group had a 31.7%lower mitochondrial MDA concentration as compared to the GL-CUR group(P<0.05).Compared to the GL group,curcumin increased(P<0.05)mitochondrial MnSOD,GPx and GR activities in the CUR-GL and GL-CUR groups,respectively.The ROS level was decreased(P<0.05)in CUR-GL group when compared with the GL group.Compared to the GL group,curcumin in the CUR-GL and GL-CUR group prevented(P<0.05)the decrease of MMP caused by the d-GalN/LPS injection.The CUR-GL group had a 36.0%lower hepatic ROS concentration and a 43.0%higher MMP when compared with the GL-CUR group(P<0.05).The CUR-GL group had a lower(P<0.05)percentage of necrotic cells while the GL-CUR group had lower(P<0.05)percentage of apoptotic and necrotic cells in comparison with the GL group.The liver mRNA levels of Sirtl were lower(P<0.05)in the CUR-GL group than that of the GL group.In conclusion,curcumin protected against d-GalN/LPS-induced liver damage by the enhancing antioxidant defense system,attenuating mitochondrial dysfunction,and inhibiting apoptosis.When compared to post-treatment with curcumin,we found that pretreatment with curcumin was much more effective in terms of hepato-protection.3 Effect of the varying levels of dietary curcumin on growth performance,meat quality and antioxidant profile of breast muscle in broilersThe aim of this study was to determine the effects of the varying levels of curcumin on growth perform,organ index,meat quality and antioxidant profile of breast muscle in broilers.Three hundred and twenty one-day-old Arbor Acres broiler chicks were randomly allotted to 4 treatments,each consisting of 8 pens as replicates,with 10 chicks in each pen.Chicken were fed with the basal diet supplemented with 0(CON),50(CUR50),100(CUR 100),and 200(CUR200)mg/kg curcumin,respectively.The whole experiment lasted for 42 days.The results showed that there were no differences in the ADFI and F/G during the whole experiment among all the groups.Compared to the CON group,the absolute and relative weights of bursa of fabricius at 21 d were increased(P<0.05).The absolute and relative weights of breast muscle at 21 d in the CUR100 group were increased(P<0.05)by 23.76%and 11.08%,respectively,as compared to the CON group.Compared to the CON group,the absolute and relative weights of spleen at 42 d were increased(P<0.05)by 22.98%and 20.16%in the CUR200 group,respectively.For meat color,a*value of breast muscle was increased(P<0.05)by 27.87%and 32.36%in the CUR100 and CUR200groups,respectively,as compared to the CON group.Compared to the CON group,the driploss at 24 and 48 h were decreased by 22.51%and 22.43%(P<0.05)in the CUR100 group,respectively.Breast muscle in the CUR200 group showed a 11.40%lower(P<0.05)pressure loss when compared to the CON group.Compared to the CON group,theDPPH· radical scavenging activities in the CUR50,CUR100 and CUR200 groups wereincreased(P<0.05)by 16.83%,41.31%and 18.00%,respectively.The ABTS radicalscavenging activities of breast meat in the CUR50 and CUR100 groups were higher(P<0.05)than that of the CON group.When compared to the CON group,breast muscle fromthe CUR50 and CUR100 groups exhibited 41.73%and 51.56%higher(P<0.05)O2·-radical scavenging activities.The CAT and GPx activities of the breast muscle were77.24%and 30.88%higher(P<0.05)in the CUR100 group than that of the CON group.The highest T-SOD activity was observed in the CUR50 group,which was increased(P<0.05)by 38.37%when compared to the CON group.In conclusion,the resulteddemonstrated that curcumin increased the organ index,improved the meat color and waterholding capacity,and enhanced the free radical scavenging activates and antioxidantenzymatic activities to some extent.4 Dietary curcumin supplementation protects against heat stress-impairedgrowth performance of broilers possibly through a mitochondrialpathwayThe aim of this study was to investigate the growth performance,antioxidant systemof the breast muscle,redox status in the mitochondrial fraction and the expression ofmitochondrial biogenesis-related genes of breast muscle in response to the varying levels ofcurcumin under heat stress.A total of 400 one-day-old Arbor Acres broiler chicks wererandomly allocated into 5 treatments,with 8 replicates of 10 birds each.Broilers in theCON and HS group were fed the basal diet while ones in HS-CUR50,HS-CUR100 andHS-CUR200 groups were fed the basal diet with 50,100 and 200 mg/kg curcumin,respectively.From ED21 to ED42,birds in CON group were housed at 22±℃ while theother were kept at 34 ± 1 ℃ for 8 h.The chronic heat treatment lasted for 20 days.Theresults showed that diets supplied with 50 and 100 mg/kg curcumin increased the F/G ascompared to the HS groups(P<0.05).Curcumin supplementation decreased(P<0.05)the ROS and 8-OHdG concentrations in breast muscle when compared to the HS group.The HS-CUR100 group had a 16.57%lower MDA levels and 8.43%lower PC contents of breast muscle(P<0.05).Birds supplied with 50,100 and 200 mg/kg curcumin had 15.81%,19.73%and 11.66%higher(P<0.05)GSH levels,and 10.59%.10.80%and 6.35%higher(P<0.05)GPx activities than those of the HS group,respectively.Compared to the HS group,the GST,T-SOD and CAT activities of breast muscle were increased(P<0.05)in the HS-CUR50 and HS-CUR100 group.Dietary curcumin intervention enhanced(P<0.05)GPx,GST and MnSOD activities in the mitochondria of breast muscle.Curcumin treatments showed an inhibitory effect(P<0.05)on mitochondrial swelling.Curcumin supplementation(50,100,200 mg/kg)resulted in significant decreases(P<0.05)in HSP70 and HSP90 mRNA levels.The avUCP mRNA levels in the HS-CUR50 and HS-CUR100 groups were increased(P<0.05)by 21.25%and 24.03%,respectively,as compared to the HS group.Compared to the HS group,broilers in the HS-CUR100 groups had higher(P<0.05)PGC-la and NRF1 mRNA levels of breast muscle.Following the heat treatment,the highest NRF2 mRNA level was found in HS-CUR100 group,and were increased(P<0.05)by 26.57%and 21.99%when compared to the HS and HS-CUR200 groups.In conclusion,curcumin supplementation prevented heat stress-impaired growth performance,possibly through improving the antioxidant defense system,mitochondrial redox status and enhancing the mitochondrial biogenesis.5 Curcumin protects against heat stress-induced oxidative damage and mitochondrial dysfunction in broiler chickensIn this study,we aimed to examine the protective effects of curcumin on oxidant damages and dysfunction in the mitochondrial fraction,and investigate the possible mechanism related to the key factors of phase Ⅱ detoxifying enzyme systems and Trx2/Prx3 antioxidant systems.The present study shared the same details of the experiment design as the one in Chapter 7.The results showed that broilers in the CUR50,CUR100 and CUR200 groups had lower(P<0.05)serum ALT,AST,MDA and cortisol contents,as compared to the HS group.Dietary curcumin supplementation prevented(P<0.05)the over-production of ROS and the depletion of mitochondrial membrane potential in liver.There were 20.41%and 27.21%lower(P<0.05)on mitochondrial MDA levels in the CUR100 and CUR200 groups than those of the HS group.The mitochondrial PC contents were decreased and T-SH contents were increased in the curcumin supplied groups(P<0.05)when compared to the HS group.There were 18.88%and 26.11%highermitochondrial NP-SH contents in the CUR100 and CUR200 groups than those of the HSgroup(P<0.05).Compared to the HS group,mitochondrial MnSOD activities wereincreased by 31.85%(P<0.05)in the HS-CUR100 group.Compared to the HS group,curcumin supplementation increased(P<0.05)the mitochondria GSH concentrations andimproved(P<0.05)the activities of GSH-related enzymes,including GCL,GPx and GST.Broilers supplied with 50,100 and 200 mg/kg curcumin had 16.78%,21.97%and 20.88%higher(P<0.05)mtDNA copy number,and 15,73%,15,79%and 14.05%higher(P<0.05)ATP levels than those of the HS group,respectively.Curcumin showed an increasing effect(P<0.05)on mRNA levels of Nrf25 HO-1 and CAT of liver.The highest Cu/ZnSODmRNA levels were found in HS-CUR100 group,and increased(P<0.05)by 22.45%whencompared to the HS group.The GCLc mRNA levels were increased(P<0.05)with theincreasing level of dietary curcumin supplementation when compared to the HS group.Broilers supplied with 50,100 and 200 mg/kg curcumin had higher(P<0.05)Trx2 andPrx3 mRNA levels than those of the HS group,respectively.There was 16.70%higher onthe Trx-R2 mRNA level in the HS-CUR50 group than that of the HS group(P<0.05).Compared to the HS group,broilers in the HS-CUR100 groups had 23.56%and 18.81%higher(P<0.05)MnSOD mRNA levels of the liver.In conclusion,curcuminsupplementation showed an inhibitory effect on the over-production of ROS,collapse ofmitochondrial member potential and the imbalance of the redox system.It was suggestedthat curcumin protected against heat stress-induced oxidant damages by simultaneousactivation of the phase II detoxifying enzyme system and mitochondrial Trx2/Prx3 system.
Keywords/Search Tags:Oxidant stress, Curcumin, Mitochondria, Antioxidant, Heat stress, Broiler chickens
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