Advertisement

European Journal of Nutrition

, Volume 58, Issue 6, pp 2425–2437 | Cite as

Restorative potentiality of S-allylcysteine against diabetic nephropathy through attenuation of oxidative stress and inflammation in streptozotocin–nicotinamide-induced diabetic rats

  • V. V. Sathibabu Uddandrao
  • Parim Brahmanaidu
  • Ramavat Ravindarnaik
  • Pothani Suresh
  • S. Vadivukkarasi
  • Ganapathy SaravananEmail author
Original Contribution

Abstract

Aim

In the present study, we evaluated the therapeutic potentiality of S-allylcysteine (SAC) in streptozotocin (STZ)–nicotinamide (NAD)-induced diabetic nephropathy (DN) in experimental rats.

Methods

SAC was orally administered for 45 days to rats with STZ–NAD-induced DN; a metformin-treated group was included for comparison. Effect of SAC on body weight, organ weight, blood glucose, levels of insulin, glycated haemoglobin, and renal biochemical markers was determined. Body composition by total body electrical conductivity (TOBEC) and dual-X ray absorptiometry (DXA), kidney antioxidant analysis, real-time polymerase chain reaction, and western blot analysis of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nuclear factor kappa B (NF-κB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α; histopathological and scanning electron microscope (SEM) analysis of the kidneys were performed in both control and experimental rats.

Results

SAC treatment showed significantly decreased levels of blood glucose, glycated haemoglobin, creatinine, albumin, AST, ALT, creatinine kinase, lactate dehydrogenase, and expressions of NF-κB, IL-6, and TNF-α compared with DN control rats. Furthermore, SAC administration to DN rats significantly improved body composition and antioxidant defense mechanism which was confirmed by the upregulation of mRNA and protein expressions of antioxidant genes.

Conclusions

Thus, SAC showed adequate therapeutic effect against DN by downregulation of inflammatory factors and attenuation of oxidative stress. Histological and SEM observations also indicated that SAC treatment notably reverses renal damage and protects the kidneys from hyperglycemia-mediated oxidative damage.

Keywords

Nephropathy Oxidative stress Natural products Metabolic disorders Anti-diabetic 

Notes

Acknowledgements

The authors thank the Department of Science and Technology (DST-SERB), Government of India (Ref no. DST/SERB/SR/SO/HS/0227/2012) and Innovation in Science Pursuit for Inspired Research (INSPIRE), Department of Science and Technology (DST). Government of India (Grant no. DST/INSPIRE/04/2016/000893) for providing the financial assistance, and also thank for the management of K. S. Rangasamy College of Arts and Science (Autonomous), Tiruchengode, for providing facilities.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

The protocol of this study was approved by the Institutional animal ethical committee of the National Centre for Laboratory Animal Science, National Institute of Nutrition, Hyderabad (Approval no. P7F/II-IAEC/NIN/2015/GS/WNIN Rats/42M) and experiments were carried out according to the guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India.

References

  1. 1.
    Tesfaye S, Gill G (2011) Chronic diabetic complications in Africa. Afr J Diabetes Med. 19:4–8Google Scholar
  2. 2.
    Fernandez Millan E, Ramos S, Alvarez C, Bravo L, Goya L (2014) Microbial phenolic metabolites improve glucose-stimulated insulin secretion and protect pancreatic beta cells against tert-butyl hydroperoxide-induced toxicity via ERKs and PKC pathways. Food Chem Toxicol 66:245–253CrossRefPubMedGoogle Scholar
  3. 3.
    Naidu PB, Uddandrao S, Ramavat VV, Naik R, Pothani S, Saravanan G et al (2016) Effects of S-allylcysteine on biomarkers of the polyol pathway in rats with type 2 diabetes. Can J Diabetes 40:442–448CrossRefPubMedGoogle Scholar
  4. 4.
    Verzola D, Gandolfo MT, Ferrario F, Rastaldi MP, Villaggio B, Gianiorio F et al (2007) Apoptosis in the kidneys of patients with type II diabetic nephropathy. Kidney Int 72:1262–1272CrossRefPubMedGoogle Scholar
  5. 5.
    Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T (2005) Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28:164–176CrossRefPubMedGoogle Scholar
  6. 6.
    Mima A (2013) Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diabetes Res 2013:1–8CrossRefGoogle Scholar
  7. 7.
    Ziyadeh FN, Wolf G (2008) Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 4:39–45CrossRefPubMedGoogle Scholar
  8. 8.
    Veerapur VP, Prabhakar KR, Thippeswamy BS, Bansal P, Srinivasan KK, Unnikrishnan MK (2010) Antidiabetic effect of Dodonaea viscose (L). Lacq. aerial parts in high fructose-fed insulin resistant rats: a mechanism based study. Indian J Exp Biol 48:800–810PubMedGoogle Scholar
  9. 9.
    Saravanan G, Ponmurugan P (2012) Ameliorative potential of S-allylcysteine: effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes. Exp Toxicol Pathol 64:639–644CrossRefPubMedGoogle Scholar
  10. 10.
    Hfaiedha N, Muratb JC, Elfekia A (2011) Protective effects of garlic (Allium sativum) extract upon lindane-induced oxidative stress and related damages in testes and brain of male rats. Pestic Biochem Physiol 100:187–192CrossRefGoogle Scholar
  11. 11.
    Kim JM, Chang N, Kim WK, Chun HS (2006) Dietary S-allyl-l-cysteine reduces mortality with decreased incidence of stroke and behavioral changes in stroke-prone spontaneously hypertensive rats. Biosci Biotechnol Biochem 70:1969–1971CrossRefPubMedGoogle Scholar
  12. 12.
    Zafar M, Naeem-ul-Hassan Naqvi S, Ahmed M, Kaim Khani ZA (2009) Altered liver morphology and enzymes in streptozotocin induced diabetic rats. Int J Morphol 27:719–725Google Scholar
  13. 13.
    Sani I, Oche O, Chiaka NG, Samuel NU (2014) Antihyperglycemic and antihyperlipidemic effects of aqueous and ethanolic leaf extracts of Vitex doniana in streptozotocin-induced diabetic rats. Res J Med Plants 8:178–186Google Scholar
  14. 14.
    Parim B, Harishankar N, Balaji M, Pothana S, Sajjalaguddam RR (2015) Effects of Piper nigrum extracts: restorative perspectives of high fat diet induced changes on lipid profile, body composition, and hormones in Sprague–Dawley rats. Pharm Biol 53:1318–1328CrossRefPubMedGoogle Scholar
  15. 15.
    Meriga B, Parim B, Chunduri VR, Naik RR, Nemani H, Suresh P, Ganapathy S, Sathibabu U (2017) Antiobesity potential of Piperonal: promising modulation of body composition, lipid profiles and obesogenic marker expression in HFD-induced obese rats. Nutr Metab 14:72CrossRefGoogle Scholar
  16. 16.
    Fraga CG, Leibouitz BE, Toppel AL (1988) Lipid peroxidation measured as TBARS in tissue slices: characterization and comparison with homogenates and microsomes. Free Radic Biol Med 4:155–161CrossRefPubMedGoogle Scholar
  17. 17.
    Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Annu Rev Biochem 202:384–387CrossRefGoogle Scholar
  18. 18.
    Beutler E, Kelly BM (1963) The effect of sodium nitrate on RBC glutathione. Experientia 19:96–97CrossRefPubMedGoogle Scholar
  19. 19.
    Aseni M, Sastre J, Pallardo FV, Lloret A, Lehner M, Garciade-la Asuncion J (1999) Ratio of reduced to oxidized glutathione as indicator of oxidative stress status and DNA damage. Methods Enzymol 299:267–276CrossRefGoogle Scholar
  20. 20.
    Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 21:130–132Google Scholar
  21. 21.
    Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefGoogle Scholar
  22. 22.
    Paglia D, Valentine W (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMedGoogle Scholar
  23. 23.
    Saravanan G, Ponmurugan P (2011) Ameliorative potential of S-allyl cysteine on oxidative stress in STZ induced diabetic rats. Chem Biol Interact 189:100–106CrossRefPubMedGoogle Scholar
  24. 24.
    Brahmanaidu P, Sathibabu Uddandrao VV, Sasikumar V, Naik RR, Pothani S, Saravanan G et al (2017) Reversal of endothelial dysfunction in aorta of streptozotocin–nicotinamide-induced type-2 diabetic rats by S-allylcysteine. Mol Cell Biochem 43:225–232Google Scholar
  25. 25.
    Larson MO, Wilken M, Gotfredsen CF, Carr RD, Svendsen O, Roli B (2002) Mild streptozotocin diabetes in the Gottingen minipig. A novel model of moderate insulin deficiency and diabetes. Am J Physiol Endocrinol Metab 282:1342–1351CrossRefGoogle Scholar
  26. 26.
    Calabresi P, Chabner BA (1991) Antineoplastic agents. In: Goodman A, Gilman's (eds) The pharmacological basis of therapeutics, vol 8. Pergamon Press, New York, pp 1209–1263Google Scholar
  27. 27.
    Augusti KT, Sheela CG (1996) Antiperoxide effect of S-allyl cysteine sulfoxide, an insulin secretagogue, in diabetic rats. Experientia 52:115–120CrossRefPubMedGoogle Scholar
  28. 28.
    Naidu PB, Sathibabu Uddandrao VV, Naik RR, Suresh P, Meriga B, Begum MS, Ganapathy Saravanan (2016) Ameliorative potential of gingerol: promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats. Mol Cell Endocrinol 419:139–147CrossRefGoogle Scholar
  29. 29.
    Sathibabu Uddandrao VV, Brahmanaidu P, Saravanan G (2017) Therapeutical perspectives of S-allylcysteine: effect on diabetes and other disorders in animal models. Cardiovasc Hematol Agents Med Chem 15:71–77CrossRefGoogle Scholar
  30. 30.
    Khanra R, Dewanjee S, Dua T, Sahu R, Gangopadhyay M, De Feo V, Zia-Ul-Haq M (2015) Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response. J Transl Med 13:1–14CrossRefGoogle Scholar
  31. 31.
    Siu B, Saha J, Smoyer WE, Sullivan KA, Brosius FC (2006) Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: prevention by lipoic acid treatment. BMC Nephrol 7:6CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gyawali P, Shrestha R, Poudel B, Sigdel M, Regmi P (2008) Serum urea and creatinine in diabetic and non-diabetic subjects. J Nepal Assoc Med Lab Sci 9:11–12Google Scholar
  33. 33.
    Ma ST, Liu DL, Deng JJ, Niu R, Liu RB (2013) Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic nephropathy rats. Phytother Res 27:1474–1480PubMedGoogle Scholar
  34. 34.
    Yamashita H, Nagai Y, Takamura T, Nohara E, Kobayashi K (2002) Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat. Metabolism 51:403–408CrossRefPubMedGoogle Scholar
  35. 35.
    Palsamy P, Subramanian S (2011) Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2–Keap1 signaling. Biochem Biophys Acta 1812:719–731PubMedGoogle Scholar
  36. 36.
    Navarro CM, Montilla PM, Martin A, Jimenez J, Utrilla PM (1993) Free radicals scavenger and antihepatotoxic activity of Rosmarinus. Plant Med Phytother 59:312–314CrossRefGoogle Scholar
  37. 37.
    Sathibabu Uddandrao VV, Brahmanaidu P, Meriga B, Saravanan G (2016) The potential role of S-allylcysteine as antioxidant against various disorders in animal models. Oxid Antioxid Med Sci 5:79–86CrossRefGoogle Scholar
  38. 38.
    Sathibabu Uddandrao VV, Brahmanaidu P, Nivedha PR, Vadivukkarasi S, Saravanan G (2018) Beneficial role of some natural products to attenuate the diabetic cardiomyopathy through Nrf2 pathway in cell culture and animal models. Cardiovasc Toxicol 18:199–205CrossRefPubMedGoogle Scholar
  39. 39.
    Rameshreddy P, Sathibabu Uddandrao VV, Brahmanaidu P, Vadivukkarasi S, Ravindarnaik R, Saravanan G et al (2017) Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague–Dawley rats. Mol Cell Biochem 442:143–154CrossRefPubMedGoogle Scholar
  40. 40.
    Lery V, Zaltzber H, Ben-Amotz A, Kanter Y, Aviram M (1999) Carotene affects antioxidant status in non-insulin dependent diabetes mellitus. Pathophysiology 6:157–162CrossRefGoogle Scholar
  41. 41.
    Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–410CrossRefPubMedGoogle Scholar
  42. 42.
    Ewis SA, Abdel Rahman MS (1995) Effect of metformin on glutathione and magnesium in normal and streptozotocin-induced diabetic rats. J Appl Toxicol 15:387–390CrossRefPubMedGoogle Scholar
  43. 43.
    Loven D, Schedl H, Wilson H, Daabees TT, Stegink LD, Diekus M (1986) Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozotocin induced diabetes. Diabetes 35:503–507CrossRefPubMedGoogle Scholar
  44. 44.
    Saxena AK, Srivastava P, Kale RK, Baquer NZ (1993) Impaired antioxidant status in diabetic rat liver: effect of vanadate. Biochem Pharmacol 45:539–542CrossRefPubMedGoogle Scholar
  45. 45.
    Wohaieb SA, Godin DV (1987) Alterations in free radical tissue-defense mechanisms in streptozotocin-induced diabetes in rat: effect of insulin treatment. Diabetes 36:1014–1018CrossRefPubMedGoogle Scholar
  46. 46.
    Sozmen BY, Sozmen B, Delen Y, Onat T (2001) Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may implicate poor glycemic control. Arch Med Res 32:283–287CrossRefPubMedGoogle Scholar
  47. 47.
    Yan H, Harding JJ (1997) Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase. Biochem J 328:599–604CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Haliga R, Mocanu V, Paduraru I, Stoica B, Oboroceanu T, Luca V (2009) Effects of dietary flaxseed supplementation on renal oxidative stress in experimental diabetes. Rev Med Chir Soc Med Nat Iasi 113:1200–1204PubMedGoogle Scholar
  49. 49.
    Juan Navarro-Gonzalez F, Carmen M-F (2008) The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 19:433–442CrossRefPubMedGoogle Scholar
  50. 50.
    Hayden MS, Ghosh S (2008) Shared principles in NF-kappa-B signaling. Cell 132:344–362CrossRefPubMedGoogle Scholar
  51. 51.
    Sanz AB, Sanchez-Nino MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM et al (2010) TWEAK activates the non-canonical NFkappa B pathway in murine renal tubular cells: modulation of CCL21. PLoS One 5:8955CrossRefGoogle Scholar
  52. 52.
    Dalla Vestra M, Mussap M, Gallina P, Brueghin M, Cernigoi AM, Saller A. Plebani M, Fioretto P (2005) Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol 16:78–82CrossRefGoogle Scholar
  53. 53.
    Navarro JF, Mora C, Maca M, Garca J (2003) Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus. Am J Kidney Dis 42:53–61CrossRefPubMedGoogle Scholar
  54. 54.
    Boyle JJ, Weissberg PL, Bennett MR (2003) Tumor necrosis factor-alpha promotes macrophage-induced vascular smooth muscle cell apoptosis by direct and autocrine mechanisms. Arterioscler Thromb Vasc Biol 23:1553–1558CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biochemistry, Centre for Biological SciencesK. S. Rangasamy College of Arts and Science (Autonomous)NamakkalIndia
  2. 2.ICMR-National Animal Resource Facility for Biomedical Research (ICMR-NARFBR)HyderabadIndia

Personalised recommendations