| Objects:Oxidative stress is the culprit of many diseases.The toxic effects caused by some widely used drugs are also closely related to the oxidative stress caused by them,such as gentamicin(GM),cisplatin(DDP),daunorubicin(DNR)and doxorubicin(DOX).Existing studies have shown that some bioactive peptides are good antioxidants,which can protect the body from oxidative damage.Therefore,in this study,animal experiments were conducted to observe the protective effect of bioactive peptides(Albumin peptides,Wheat oligopeptides,Soy peptides,Corn oligopeptides)against gentamicin,cisplatin,doxorubicin and daunorubicin toxicity,and to further explore the relationship between their protective effect and antioxidant activity.Methods:1.Study on the protective effect of four bioactive peptides on the toxicity effects of gentamicin.(1)Study on the protective effect of soybean peptides on the ototoxicity induced by gentamicin.The number of nerve colliculus hair cells in zebrafish were observed by treating them with gentamicin and soy peptides.(2)Protective effects of four bioactive peptides on gentamicin-induced nephrotoxicity.(a)Grouping and administration:42 C57BL/6 male mice were randomly divided into 6 groups,A:Normal control group was intraperitoneally injected with appropriate amount of normal saline per day.30 min later,an appropriate amount of distilled water was given by gavage,once every other day.B:GM group was intraperitoneally injected with 100 mg/kg of GM every day.30 min later,an appropriate amount of distilled water was given by gavage,once every other day.C:GM+Albumin peptides group,100 mg/kg dose of GM was intraperitoneally injected every day,and 600 mg/kg dose of Albumin peptides was gavage 30 min later,once every other day.D:GM+Wheat oligopeptides group was intraperitoneally injected with 100 mg/kg of GM every day.30 min later,600 mg/kg Wheat oligopeptides was given intragastric administration,once every other day.E:GM+Soy peptides group was intraperitoneally injected with 100 mg/kg of GM per day.30 min later,600 mg/kg Soy peptides was given intragastrically,once every other day.F:GM+Corn oligopeptides group was intraperitoneally injected with 100 mg/kg of GM per day.30 min later,600 mg/kg of Corn oligopeptides was given intragastric administration,once every other day.The above treatment was carried out for 10 days.(b)Index observation and detection:body weight changes of mice were recorded every three days;The contents of Blood Urea Nitrogen(BUN)and Creatinine(Cr)in serum were detected to observe the changes of renal function.The contents of Total Antioxidant Capacity(T-AOC)and Glutathione(GSH)in serum and Superoxide dismutase in renal were detected.The activity of Superoxide Dismutase(SOD)and the content of Malondialdehyde(MDA)were used to evaluate the changes of antioxidant capacity.Periodic Acid-Schiff(PAS)Stain was used to observe the histopathological changes of kidney.2.Protective effects of four bioactive peptides on the toxicity effects of cisplatin.(1)Grouping and administration:42 C57BL/6 male mice were randomly divided into 6groups.A:Normal control group was intraperitoneally injected with appropriate amount of normal saline per day.30 min later,an appropriate amount of distilled water was given by gavage,once every other day.B:DDP group was injected intraperitoneally at 4 mg/kg daily.30 min later,600 mg/kg of distilled water was given by gavage,once every other day.C:DDP+Albumin peptides group,DDP was intraperitoneally injected at 4 mg/kg daily.30 min later,600 mg/kg Albumin peptide was given intragastric administration,once every other day.D:DDP+Wheat oligopeptides group was intraperitoneally injected with 4 mg/kg DDP every day.30 min later,600 mg/kg Wheat oligopeptides was given intragastric administration,once every other day.E:DDP+Soy peptides group was intraperitoneally injected with DDP at 4 mg/kg daily.30 min later,600 mg/kg Soy peptides was given intragastrically,once every other day.F.:DDP+Corn oligopeptides group was intraperitoneally injected with 4 mg/kg of DDP every day.30 min later,600mg/kg of Corn oligopeptides was given intragastric administration,once every other day.The above treatment was carried out for 5 days.(2)Index observation and detection:the change of body mass was recorded every 2 days;The changes in the number of peripheral blood cells were detected to evaluate myelosuppressive toxicity.The contents of BUN and Cr in serum were detected to observe the changes of renal function.Adenine Nucleoside Triphosphate(ATP)content and Na~+K~+-ATPase activity were detected to observe the changes of renal mitochondria.Serum Catalase(CAT)activity,GSH content,SOD activity and MDA content in kidney were detected to evaluate the changes of antioxidant capacity.The histopathological changes of kidney were observed by PAS staining.3.Study on the protective effects of four bioactive peptides on the toxic effects of adriamycin.(1)Effects of four bioactive peptides on the survival rate of mice.(a)Grouping and administration.36 C57BL/6 mice were randomly divided into 6 groups.A:normal control group was injected intraperitoneally with appropriate amount of normal saline every day.30 min later,an appropriate amount of distilled water was given by gavage,once every other day.B:DOX group was intraperitoneally injected with 17mg/kg DOX every day.30 min later,600 mg/kg of distilled water was given by gavage,once every other day.C:DOX+Albumin peptides group was intraperitoneally injected with DOX at 17 mg/kg daily.30 min later,600 mg/kg Albumin peptides was given intragastric administration,once every other day.D:DOX+Wheat oligopeptides group was intraperitoneally injected with DOX at 17 mg/kg every day.30 min later,600 mg/kg Wheat oligopeptides was given intragastric administration,once every other day.E:DOX+Soy peptides group was intraperitoneally injected with DOX at 17 mg/kg daily.30 min later,600 mg/kg Soy peptides was given intragastrically,once every other day.F:DOX+Corn oligopeptides group was intraperitoneally injected with 17 mg/kg DOX every day.30 min later,600 mg/kg of Corn oligopeptides was given intragastric administration,once every other day.The above treatment was carried out for 7 days.(b)Observation indexes:survival rate of mice was observed every day.(2)Protective effects of four bioactive peptides on the myelosuppressive and cardiotoxic effects of daunorubicin.(a)Grouping and administration:the method of grouping and administration in survival observation was adopted,and the treatment time was changed to 4 days.(b)Index observation and detection:changes in the number of peripheral blood cells were detected to evaluate myelosuppressive toxicity;Left Ventricular Ejection Fraction(LVEF)and Left Ventricular Fractional shortening(LVFS)were measured by ultrasound to evaluate cardiac function.Serum Lactate dehydrogenase(LDH)activity was detected to assess myocardial injury;The changes of serum GSH content,SOD activity and MDA content in myocardial were detected to evaluate the changes of antioxidant capacity.Histopathological changes of myocardium were observed by Hematoxylin-Eosin(HE)staining.4.Study on the protective effect of bioactive peptides against the toxic effects of daunorubicin.The same experimental scheme as in Method 3 was adopted,only the modeling method was changed to intraperitoneal injection of DNR at 11 mg/kg.Results:1.Bioactive peptides have obvious protective effects on the toxic effects of gentamicin,which are shown in the following aspects:(1)The number of nerve colliculus hair cells decreased significantly after GM treatment;The number of cumulus hair cells in zebrafish was significantly increased after soy peptides was added.(2)In the model of gentamicin-induced nephrotoxicity:(a)GM significantly reduced renal function in mice;Four bioactive peptides could significantly improve renal function in mice.(b)GM induced renal lesions in mice;All the four biological activities could improve the renal lesions induced by GM in mice.(c)GM significantly reduced the antioxidant capacity of mice,and all the four bioactive peptides could significantly improve the antioxidant capacity of mice.2.Bioactive peptides have obvious protective effects on the toxic effects of cisplatin,which are shown in the following aspects:(1)DDP significantly reduced the amount of WBC and PLT in peripheral blood,and all four bioactive peptides significantly increased the amount of WBC and PLT in peripheral blood of mice.(2)DDP significantly reduced renal function in mice;Four bioactive peptides significantly improved renal function in mice.(3)DDP leads to abnormal mitochondrial metabolism in mice,and all the four biological activities can improve the abnormal mitochondrial metabolism in mice caused by DDP.(4)DDP caused renal lesions in mice;All the four biological activities can improve the pathological changes of mice kidney caused by DDP.(5)DDP significantly reduced the antioxidant capacity of mice,and all the four bioactive peptides could significantly improve the antioxidant capacity of mice.3.Bioactive peptides have certain protective effects on the toxic effects of doxorubicin,which are shown as follows:(1)Four bioactive peptides can improve the survival rate of mice.(2)Four bioactive peptides have protective effects on DOX myelosuppressive toxicity and cardiotoxicity.(a)DOX significantly reduced the amount of peripheral blood cells in mice,and all the four bioactive peptides significantly increased the amount of peripheral blood cells in mice.(b)The heart function of mice in DOX group was significantly decreased,while the heart function of mice in the Four groups of bioactive peptides was significantly increased.(c)DOX significantly increased serum LDH activity in mice;Four bioactive peptides significantly reduced serum LDH activity in mice.(d)DOX caused cardiac lesions in mice;All the four bioactive peptides had no improvement on DOX-induced cardiac tissue lesions in mice.(e)DOX significantly reduced the antioxidant capacity of mice,and all the four bioactive peptides could significantly improve the antioxidant capacity of mice.4.Bioactive peptides have obvious protective effects on the toxic effects of daunorubicin,which are shown as follows:(1)Four bioactive peptides can improve the survival rate of mice.(2)Four bioactive peptides had protective effects on the myelosuppressive toxicity and cardiotoxicity of DNR.(a)DNR significantly reduced the number of peripheral blood cells in mice,and all four bioactive peptides significantly increased the amount of peripheral blood cells in mice.(b)Cardiac function was significantly decreased in DNR group,and significantly increased in the 4 groups of bioactive peptides.(c)DNR significantly increased serum LDH activity in mice;Four bioactive peptides significantly reduced serum LDH activity in mice.(d)DNR induced cardiac lesions in mice;All the four bioactive peptides could improve the pathological changes of mice heart caused by DNR.(e)DNR significantly reduced the antioxidant capacity of mice,and all the four bioactive peptides could significantly improve the antioxidant capacity of mice.Conclusion:Four bioactive peptides(Albumin peptides,wheat oligopeptides,soybean peptides and corn oligopeptides)have obvious protective effects to gentamicin nephrotoxicity and ototoxicity,cisplatin cardiotoxicity and nephrotoxicity,doxorubicin and daunorubicin cardiotoxicity and myelosuppressive toxicity,and the protective effects of the four bioactive peptides are related to their antioxidant activity. |
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