Effect Of Beta-Carotene On Adriamycin Induced Changes Of Expression Of MRNA Of Superoxide Dismutase And Glutathione Peroxidase In Myocardial Tissue Of Rats

Objective:To study the effect of beta-carotene(BC) on adriamycin(ADM)induced changes of expression of manganese superioxide dismutase(Mn SOD)mRNA,copper-zinc superioxide dismutase(Cu-Zn SOD) mRNA and glutathioneperoxidase(GPx) mRNA in myocardial tissue of rats,and to explore themechanism of BC antagonizing the reduced activities of Mn SOD,Cu-Zn SOD,GPx in myocardial tissue of rats induced by ADM.Methods: Sixty-four Sprague-Dawley(SD) rats were randomly divided intoeight groups.BC and alpha-tocopherol(AT)were emulsified with sterile beamoil,ADM was dissolved in sterile isotonic saline.Administration of AT and BCwas the same volume(3.0ml.kg-1,intragastric perfusion(ig)),Administraion ofADM was the same volume too(6.0ml.kg-1,intraperitoneal injection(ip)).①Controlgroup:ig sterile bean oil (3.0ml.kg-1 ) every day for 14 times,ip sterile isotonicsaline(6.0ml.kg-1) 1 time on 12th day;②ADM treated group:ig sterile beamoil(3.0ml.kg-1 ) every day for 14 times, ip ADM (10mg.kg-1) 1 time on 12th day;③ADM with BC treated group(Ⅰ): ig BC(20.0mg.kg-1),every day for 14 times;④ADM with BC treated group(Ⅱ): ig BC(40.0mg.kg-1),every day for 14 times;⑤ADM with BC treated group(Ⅲ): ig BC(80.0mg.kg-1),every day for 14 times;⑥ADM with AT treated group(Ⅰ): ig AT(75.0 mg.kg-1),every day for 14 times;⑦ADM withAT treated group(Ⅱ): igAT(150.0 mg.kg-1),every day for 14 times;⑧ADM withAT treated group(Ⅲ): igAT(300.0 mg.kg-1),every day for 14 times.The dosage and method of ADM in from the ③group to the ⑧group was thesame as the ②group.All animals were sacrificed in 72 hours after ip ADM(15thday).Thiobarbituric acid(TBA) method ,nitrite reductase method were used todetermine the contents of malondialdehyde(MDA) and nitric oxide(NO); xanthineoxidase method, 5,5 ′-dithiobis-(2-nitrobenzoic acid) (DTNB) method,enzymic rate method,hemoglobin-oxidation method were used to determine theactivities of copper-zinc superoxide dismutase(Cu-Zn SOD) and manganesesuperoxide dismutase(Mn SOD),glutathione peroxidase(GPx),creatine kinaseisoenzymic MB(CK-MB),constructive nitric oxide synthase(cNOS) and inducednitric oxide synthase(iNOS).Using reverse transcription polymerase chainreaction(RT-PCR) technique,we analyzed the expression of Mn SOD mRNA,Cu-Zn SOD mRNA,GPx mRNA and iNOS mRNA.Results: In ADM group,expressive level of iNOS mRNA,activity of iNOS,contents of MDA and NO in myocardial tissue,activity of CK-MB in serum weresignificantly increased than those in control group(P<0.01), expressive levels ofMn SOD mRNA,Cu-Zn SOD mRNA,GPx mRNA and activities of Mn SOD,Cu-Zn SOD,GPx in myocardial tissue were significantly reduced than those incontrol group(P<0.01), activity of cNOS in myocardial tissue was indifferent ascontrol group(P>0.05). In ADM with BC treated three group(Ⅰ,Ⅱ,Ⅲ),expressive level of iNOS mRNA,activity of iNOS,contents of MDA and NO inmyocardial tissue,activity of CK-MB in serum were significantly reduced thanthose in ADM group(P<0.01), expressive levels of Mn SOD mRNA,Cu-ZnSODmRNA,GPx mRNA and activities of Mn SOD,Cu-Zn SOD,GPx in myocardialtissue were significantly increased than those in ADM group(P<0.01), activityof cNOS in myocardial tissue was indifferent as ADM group(P>0.05). In ADMwith AT treated three group(Ⅰ,Ⅱ,Ⅲ), content of MDA in myocardial tissue andactivity of CK-MB in serum were significantly reduced than those in ADMgroup(P<0.01), expressive levels of Mn SOD mRNA,Cu-Zn SOD mRNA,GPxmRNA and activities of Mn SOD,Cu-Zn SOD,GPx,iNOS,cNOS and content ofNO in myocardial tissue were indifferent as ADM group(P>0.05).Conclusion: AT posses antioxidant activity.Antioxidant activity can notantagonize the reduced expression levers of Mn SOD mRNA,Cu-Zn SODmRNA,GPx mRNA and the reduced activities of Mn SOD,Cu-Zn SOD,GPx inmyocardial tissue induced by ADM.BC can antagonize the reduced expression ofMn SOD mRNA,Cu-Zn SOD mRNA,GPx mRNA in myocardial tissue inducedby ADM, thereby antagonize the reduced activities of Mn SOD,Cu-Zn SOD,GPxin myocardial tissue induced by ADM.The mechanism is rela...