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Antidiabetic and oxidative stress assessment of bio-enzymatically synthesized zinc oxide nanoformulation on streptozotocin-induced hyperglycemic mice

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Abstract

Oxidative stress has significant contribution in on-set and progression of diabetes. The disease onset leads to elevated levels of free radicals rendering the oxidant-inducing mechanisms incapable of protecting cellular organelles from inflicted damage. Herein, β-galactosidase-mediated bio-enzymatic synthesis of zinc oxide nanoparticles (ZnO NPs) was pioneered and characterized. These obtained ZnO NPs were assessed for their antidiabetic activity against streptozotocin (STZ)-induced diabetic mice. For this objective, 36 male albino mice were separated into 6 groups. The diabetes was induced in mice with STZ (120 mg kg−1 body weight), and further treated with three different doses of ZnO NPs (0.5 mg kg−1, 1 mg kg−1, and 2 mg kg−1) for 28 days. The results unveiled protective effects in diabetic mice treated with ZnO NPs through restoration of changes in body weight and normal glucose levels. The effects of ZnO NPs on lipid peroxidation and carbonyl contents were protective in liver, kidney and pancreas of diseased groups. Levels of serum biomarkers such as cholesterol, triglycerides and HDL-C indicated ZnO NPs treatment caused these levels to plummet towards control parameters. Normal liver function markers and urea levels in serum indicated successful treatment of diabetic mice with ZnO NPs. Histopathological studies revealed protective and non-toxic effects of ZnO NPs over vital tissues of kidney, liver, and pancreas. The results divulge efficacious pharmaceutical potential of ZnO NPs against formation of reactive oxygen species by scavenging free radicals enhancing the functioning of antioxidant fortifying enzymes generating sustenance over hyperglycemic conditions.

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References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    CAS  Google Scholar 

  • Ahmad MF, Ansari MO, Jameel S, Wani AL, Parveen N, Siddique HR, Shadab GGHA (2018) Protective role of nimbolide against chemotherapeutic drug hydroxyurea induced genetic and oxidative damage in an animal model. Environ Toxicol Pharmacol 60:91–99

    CAS  Google Scholar 

  • Ahmed F, Husain Q (2019) Suppression in advanced glycation adducts of human serum albumin by bio-enzymatically synthesized gold and silver nanoformulations: a potential tool to counteract hyperglycemic condition. Biochimie 162:66–76

    CAS  Google Scholar 

  • Ahmed F, Qayyum S, Husain Q (2018) Benign nano-assemblages of silver induced by β galactosidase with augmented antimicrobial and industrial dye degeneration potential. Mater Sci Eng C 91:570–578

    CAS  Google Scholar 

  • Ansari SA, Husain Q (2012) Potential applications of enzymes immobilized on/in nano materials: a review. Biotechnol Adv 30(3):512–523

    CAS  Google Scholar 

  • Ansari SA, Husain Q, Qayyum S, Azam A (2011) Designing and surface modification of zinc oxide nanoparticles for biomedical applications. Food Chem Toxicol 49(9):2107–2115

    CAS  Google Scholar 

  • Barwal I, Sood A, Sharma M, Singh B, Yadav SC (2013) Development of stevioside pluronic-F-68 copolymer based PLA-nanoparticles as an antidiabetic nanomedicine. Colloids Surf B Biointerfaces 101:510–516

    CAS  Google Scholar 

  • Bathina S, Srinivas N, Das UN (2017) Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats. Biochem Biophys Res Commun 486(2):406–413

    CAS  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    CAS  Google Scholar 

  • Egefjord L, Petersen AB, Bak AM, Rungby J (2010) Zinc, alpha cells and glucagon secretion. Curr Diabetes Rev 6(1):52–57

    CAS  Google Scholar 

  • Farooqui Z, Ahmed F, Rizwan S, Shahid F, Khan AA, Khan F (2017) Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney. Biomed Pharmacother 85:7–15

    CAS  Google Scholar 

  • Ferdinando G, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058–1070

    Google Scholar 

  • Freeland RA, Harper AE (1959) Metabolic adaptations in higher animals V: the study of metabolic pathways by means of metabolic adaptations. J Biol Chem 234:1350–1354

    Google Scholar 

  • Gaillet S, Rouanet JM (2015) Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms—a review. Food Chem Toxicol 77:58–63

    CAS  Google Scholar 

  • Gray P (1954) The Microtomist’s formulary and guide. Blakiston, New York, pp 403–409

    Google Scholar 

  • Haider T, Husain Q (2007) Preparation of lactose-free milk by using salt-fractionated almond (Amygdalus communis) β-galactosidase. J Sci Food Agric 87:1278–1283

    CAS  Google Scholar 

  • Haider T, Husain Q (2009) Hydrolysis of milk/whey lactose by β galactosidase: a comparative study of stirred batch process and packed bed reactor prepared with calcium alginate entrapped enzyme. Chem Eng Process 48(1):576–580

    CAS  Google Scholar 

  • Hartmut J, Ramachandran A (2011) Reactive oxygen species in the normal and acutely injured liver. J Hepatol 55(1):227–228

    Google Scholar 

  • He X, Li J, Wang B, Yao Q, Li L, Song R, Shi X, Zhang JA (2017) Diabetes self-management education reduces risk of all-cause mortality in type 2 diabetes patients: a systematic review and meta-analysis. Endocrine 55(3):712–731

    CAS  Google Scholar 

  • Husain Q (2010) β Galactosidases and their potential applications: a review. Crit Rev Biotechnol 30(1):41–62

    CAS  Google Scholar 

  • Husain Q (2018) Nanocarriers immobilized proteases and their industrial applications: an overview. J Nanosci Nanotechnol 18(1):486–499

    CAS  Google Scholar 

  • Husain Q, Ansari SA, Alam F, Azam A (2011) Immobilization of Aspergillus oryzae β galactosidase on zinc oxide nanoparticles via simple adsorption mechanism. Int J Biol Macromol 49(1):37–43

    CAS  Google Scholar 

  • Jansen J, Karges W, Rinkm L (2009) Zinc and diabetes-clinical links and molecular mechanisms. J Nutr Biochem 20(6):399–417

    CAS  Google Scholar 

  • Jialal I, Sokoll LJ (2015) Clinical utility of lactate dehydrogenase: a historical perspective. Am J Clin Path 143(2):158–159

    Google Scholar 

  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169

    CAS  Google Scholar 

  • Jones AAD, Mi G, Webster TJ (2018) A status report on FDA approval of medical devices containing nanostructured materials. Trends Biotechnol 37(2):117–120

    Google Scholar 

  • Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC (2012) Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 41(7):2971–3010

    CAS  Google Scholar 

  • Kind PRN, King EJ (1954) Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. J Clin Pathol 7:322

    CAS  Google Scholar 

  • Kornberg A (1955) Lactic dehydrogenase of muscle. Methods Enzymol 1:441–443

    CAS  Google Scholar 

  • Levine RL, Williams JA, Stadtman EP, Shacter E (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 233:346–357

    CAS  Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. FEBS J 47:469–474

    CAS  Google Scholar 

  • Meyer JA, Spence DM (2009) A perspective on the role of metals in diabetes: past findings and possible future directions. Metallomics 1:32–41

    CAS  Google Scholar 

  • Nagajyothi PC, Cha SJ, Yang IJ, Sreekanth TV, Kim KJ, Shin HM (2015) Antioxidant and anti-inflammatory activities of zinc oxide nanoparticles synthesized using Polygala tenuifolia root extract. J Photochem Photobiol B Biol 146:10–17

    CAS  Google Scholar 

  • Nancy L, Keating A, O’Malley J, Smith MR (2006) Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24(27):4448–4456

    Google Scholar 

  • Nickerson HD, Dutta S (2012) Diabetic complications: current challenges and opportunities. J Cardiovasc Transl Res 5(4):375–379

    Google Scholar 

  • Niedowicz DM, Daleke DL (2005) The role of oxidative stress in diabetic complications. Cell Biochem Biophys 43(2):289–330

    CAS  Google Scholar 

  • Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63

    Article  CAS  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total protein bound and non-protein bound SH groups in tissue with Ellman’s reagent. Ann Biochem 2:192–205

    Google Scholar 

  • Seo K, Choi M, Jung UJ, Kim H, Yeo J, Jeon S, Lee M (2008) Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res 52:995–1004

    CAS  Google Scholar 

  • Sharma V, Anderson D, Dhawan A (2012) Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis 17(8):852–870

    CAS  Google Scholar 

  • Shonk CC, Boxer GE (1964) Enzyme patterns in human tissues I: methods for the determination of glycolytic enzymes. Cancer Res 24:709–721

    CAS  Google Scholar 

  • Shull KH, Ashmore J, Mayer J (1956) Hexokinase, glucose-6-phosphatase and phosphorylase levels in hereditary obese hyperglycemic mice. Arch Biochem Biophys 62:210–216

    CAS  Google Scholar 

  • Tahrani AA, Bailey CJ, Prato SD, Barnett AH (2011) Management of type 2 diabetes: new and future developments in treatment. Lancet 378(9786):182–197

    CAS  Google Scholar 

  • Trinder P (1969) Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 6:24–27

    CAS  Google Scholar 

  • Valavanidisa A, Vlahogiannia T, Dassenakisb M, Scoullosb M (2006) Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants. Ecotoxicol Environ Saf 64:178–189

    Google Scholar 

  • Valgimigli L, Baschieria A, Amorati R (2018) Antioxidant activity of nanomaterials. J Mater Chem B 6:2036–2051

    CAS  Google Scholar 

  • Ventola CL (2017) Progress in nanomedicine: approved and investigational nanodrugs. P&T Peer Rev J Formul Manag 42(12):742–755

    Google Scholar 

  • Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA (2018) Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 9(2):119

    Google Scholar 

  • Zhang ZY, Xiong HM (2015) Photoluminescent ZnO nanoparticles and their biological applications. Materials 8(6):3101–3127

    CAS  Google Scholar 

  • Zhang J, Qin X, Wang B, Xu G, Qin Z, Wang J, Wu L, Ju X, Bose DD, Qiu F, Zhou H, Zou Z (2017) Zinc oxide nanoparticles harness autophagy to induce cell death in lung epithelial cells. Cell Death Dis 8(7):e2954

    CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge University Sophisticated Instrumentation Facility, Department of Biochemistry, Department of Zoology and Department of Chemistry, Aligarh Muslim University, India, for allowing the use of instrumentation required for this work. The authors gratefully acknowledge University Grants Commission (UGC), New Delhi, India, for the award of Junior Research Fellowship to F.A.

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Authors and Affiliations

  1. Department of Biochemistry, Aligarh Muslim University, Aligarh, India

    Faizan Ahmed & Qayyum Husain

  2. Department of Zoology, Aligarh Muslim University, Aligarh, India

    Mohd Owais Ansari & G. G. H. A. Shadab

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  1. Faizan Ahmed
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  2. Qayyum Husain
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  3. Mohd Owais Ansari
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  4. G. G. H. A. Shadab
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Correspondence to Qayyum Husain.

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Ahmed, F., Husain, Q., Ansari, M.O. et al. Antidiabetic and oxidative stress assessment of bio-enzymatically synthesized zinc oxide nanoformulation on streptozotocin-induced hyperglycemic mice. Appl Nanosci 10, 879–893 (2020). https://doi.org/10.1007/s13204-019-01169-0

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