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Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats

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Abstract

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.

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References

  1. Ziamajidi N, Khaghani S, Hassanzadeh G, Vardasbi S, Ahmadian S, Nowrouzi A, et al. Amelioration by chicory seed extract of diabetes- and oleic acid-induced non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) via modulation of PPAR alpha and SREBP-1. Food Chem Toxicol. 2013;58:198–209.

    Article  CAS  PubMed  Google Scholar 

  2. Madar Z, Kalet-Litman S, Stark AH. Inducible nitric oxide synthase activity and expression in liver and hepatocytes of diabetic rats. Pharmacology. 2005;73(2):106–12.

    Article  CAS  PubMed  Google Scholar 

  3. Ghamarian A, Abdollahi M, Su X, Amiri A, Ahadi A, Nowrouzi A. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats. DARU. 2012;20(1):56.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Singh VK, Singh DK. Pharmacological effects of garlic (Allium sativum L.). Annu Rev Biomed Sci. 2008;10:6–26.

    Article  CAS  Google Scholar 

  5. El-Demerdash FM, Yousef MI, El-Naga NI. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. Food Chem Toxicol. 2005;43(1):57–63.

    Article  CAS  PubMed  Google Scholar 

  6. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.

    Article  CAS  PubMed  Google Scholar 

  7. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.

    Article  CAS  PubMed  Google Scholar 

  8. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103–11.

    Article  CAS  PubMed  Google Scholar 

  9. Abbasalipourkabir R, Moradi H, Zarei S, Asadi S, Salehzadeh A, Ghafourikhosroshahi A, et al. Toxicity of zinc oxide nanoparticles on adult male Wistar rats. Food Chem Toxicol. 2015;84:154–60.

    Article  CAS  PubMed  Google Scholar 

  10. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5(1):62–71.

    Article  CAS  PubMed  Google Scholar 

  11. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  12. Bailey CJ, Day C. Metformin: its botanical background. Pract Diabet Int. 2004;21(3):115–7.

    Article  Google Scholar 

  13. Behrouj H, Ziamajidi N, Abbasalipourkabir R, Nasiri A, Soleimani Asl S. Therapeutic effect of Silybum marianum plant extract on tamoxifen-induced fatty liver inr. Avicenna J Med Biochem. 2015;3(1):e27160.

    Article  Google Scholar 

  14. Eidi A, Eidi M, Esmaeili E. Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine. 2006;13(9):624–9.

    Article  CAS  PubMed  Google Scholar 

  15. Tripathi V, Verma J. Different models used to induce diabetes: a comprehensive review. Int J Pharm Pharm Sci. 2014;6(6):29–32.

    Google Scholar 

  16. Mojani MS, Sarmadi VH, Vellasamy S, Sandrasaigaran P, Rahmat A, Peng LS, et al. Evaluation of metabolic and immunological changes in streptozotocin-nicotinamide induced diabetic rats. Cell Immunol. 2014;289:145–9.

    Article  CAS  PubMed  Google Scholar 

  17. Rezagholizadeh L, Pourfarjam Y, Nowrouzi A, Nakhjavani M, Meysamie A, Ziamajidi N, et al. Effect of Cichorium intybus L. on the expression of hepatic NF-κB and IKKβ and serum TNF-α in STZ− and STZ+ niacinamide-induced diabetes in rats. Diabetol Metab Syndr. 2016;8:11.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Pourfarjam Y, Rezagholizadeh L, Nowrouzi A, Meysamie A, Ghaseminejad S, Ziamajidi N, et al. Effect of Cichorium intybus L. seed extract on renal parameters in experimentally induced early and late diabetes type 2 in rats. Ren Fail. 2017;39(1):211–21.

    Article  PubMed  Google Scholar 

  19. Prakasam A, Sethupathy S, Pugalendi KV. Influence of Casearia esculenta root extract on protein metabolism and marker enzymes in streptozotocin-induced diabetic rats. Pol J Pharmacol. 2004;56(5):587–94.

    CAS  PubMed  Google Scholar 

  20. Du X-L, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, et al. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci. 2000;97(22):12222–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Anwar MM, Meki AR. Oxidative stress in streptozotocin-induced diabetic rats: effects of garlic oil and melatonin. Comp Biochem Physiol A: Mol Integr Physiol. 2003;135(4):539–47.

    Article  Google Scholar 

  22. Koya D, Hayashi K, Kitada M, Kashiwagi A, Kikkawa R, Haneda M. Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats. J Am Soc Nephrol. 2003;14(suppl 3):S250–3.

    Article  CAS  PubMed  Google Scholar 

  23. Raju TN, Kanth VR, Lavanya K. Effect of methanolic extract of Allium sativum (AS) in delaying cataract in STZ-induced diabetic rats. J Ocul Biol Dis Inform. 2008;1(1):46–54.

    Article  Google Scholar 

  24. Masjedi F, Gol A, Dabiri S, Javadi A. Preventive effect of garlic on histopathology of liver and markers of hepatic injury in streptozotocin-induced diabetic rats. Iran J Endocrinol Metab. 2009;11(4):433–41.

    Google Scholar 

  25. Yang J, Wang T, Rao K, Zhan Y, Chen RB, Liu Z, et al. S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology. 2013;1(3):487–94.

    Article  CAS  PubMed  Google Scholar 

  26. Saravanan G, Ponmurugan P. S-allylcysteine improves streptozotocin-induced alterations of blood glucose, liver cytochrome P450 2E1, plasma antioxidant system, and adipocytes hormones in diabetic rats. Int J Endocrinol Metab. 2013;11(4):e10927.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dias AS, Porawski M, Alonso M, Marroni N, Collado PS, Gonzalez-Gallego J. Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats. J Nutr. 2005;135(10):2299–304.

    Article  CAS  PubMed  Google Scholar 

  28. Nasiri A, Ziamajidi N, Abbasalipourkabir R, Goodarzi MT, Saidijam M, Behrouj H, et al. Beneficial effect of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of type 1 diabetic rats. Indian J Clin Biochem. 2016;1–8. doi:10.1007/s12291-016-0621-6

  29. Ingaramo PI, Ronco MT, Frances DE, Monti JA, Pisani GB, Ceballos MP, et al. Tumor necrosis factor alpha pathways develops liver apoptosis in type 1 diabetes mellitus. Mol Immunol. 2011;48(12–13):1397–407.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The present study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 9504081809).

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Correspondence to Nasrin Ziamajidi.

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Ziamajidi, N., Behrouj, H., Abbasalipourkabir, R. et al. Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats. Ind J Clin Biochem 33, 147–153 (2018). https://doi.org/10.1007/s12291-017-0656-3

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