Top

Published in:

01-09-2019 | Original Contribution

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

Authors: V. V. Sathibabu Uddandrao, Parim Brahmanaidu, Ramavat Ravindarnaik, Pothani Suresh, S. Vadivukkarasi, Ganapathy Saravanan

Published in: European Journal of Nutrition | Issue 6/2019

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.

Tesfaye S, Gill G (2011) Chronic diabetic complications in Africa. Afr J Diabetes Med. 19:4–8

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 66:245–253CrossRefPubMed

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 40:442–448CrossRefPubMed

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 72:1262–1272CrossRefPubMed

Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T (2005) Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28:164–176CrossRefPubMed

Mima A (2013) Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diabetes Res 2013:1–8CrossRef

Ziyadeh FN, Wolf G (2008) Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 4:39–45CrossRefPubMed

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 48:800–810PubMed

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 64:639–644CrossRefPubMed

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 100:187–192CrossRef

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 70:1969–1971CrossRefPubMed

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 27:719–725

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 8:178–186

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 53:1318–1328CrossRefPubMed

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 14:72CrossRef

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 4:155–161CrossRefPubMed

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 202:384–387CrossRef

18.

Beutler E, Kelly BM (1963) The effect of sodium nitrate on RBC glutathione. Experientia 19:96–97CrossRefPubMed

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 299:267–276CrossRef

20.

Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 21:130–132

21.

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

22.

Paglia D, Valentine W (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMed

23.

Saravanan G, Ponmurugan P (2011) Ameliorative potential of S-allyl cysteine on oxidative stress in STZ induced diabetic rats. Chem Biol Interact 189:100–106CrossRefPubMed

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 43:225–232

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 282:1342–1351CrossRef

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 1209–1263

27.

Augusti KT, Sheela CG (1996) Antiperoxide effect of S-allyl cysteine sulfoxide, an insulin secretagogue, in diabetic rats. Experientia 52:115–120CrossRefPubMed

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 419:139–147CrossRef

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 15:71–77CrossRef

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 13:1–14CrossRef

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 7:6CrossRefPubMedPubMedCentral

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 9:11–12

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 27:1474–1480PubMed

34.

Yamashita H, Nagai Y, Takamura T, Nohara E, Kobayashi K (2002) Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat. Metabolism 51:403–408CrossRefPubMed

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 1812:719–731PubMed

36.

Navarro CM, Montilla PM, Martin A, Jimenez J, Utrilla PM (1993) Free radicals scavenger and antihepatotoxic activity of Rosmarinus. Plant Med Phytother 59:312–314CrossRef

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 5:79–86CrossRef

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 18:199–205CrossRefPubMed

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 442:143–154CrossRefPubMed

40.

Lery V, Zaltzber H, Ben-Amotz A, Kanter Y, Aviram M (1999) Carotene affects antioxidant status in non-insulin dependent diabetes mellitus. Pathophysiology 6:157–162CrossRef

41.

Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–410CrossRefPubMed

42.

Ewis SA, Abdel Rahman MS (1995) Effect of metformin on glutathione and magnesium in normal and streptozotocin-induced diabetic rats. J Appl Toxicol 15:387–390CrossRefPubMed

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 35:503–507CrossRefPubMed

44.

Saxena AK, Srivastava P, Kale RK, Baquer NZ (1993) Impaired antioxidant status in diabetic rat liver: effect of vanadate. Biochem Pharmacol 45:539–542CrossRefPubMed

45.

Wohaieb SA, Godin DV (1987) Alterations in free radical tissue-defense mechanisms in streptozotocin-induced diabetes in rat: effect of insulin treatment. Diabetes 36:1014–1018CrossRefPubMed

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 32:283–287CrossRefPubMed

47.

Yan H, Harding JJ (1997) Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase. Biochem J 328:599–604CrossRefPubMedPubMedCentral

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 113:1200–1204PubMed

49.

Juan Navarro-Gonzalez F, Carmen M-F (2008) The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 19:433–442CrossRefPubMed

50.

Hayden MS, Ghosh S (2008) Shared principles in NF-kappa-B signaling. Cell 132:344–362CrossRefPubMed

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 5:8955CrossRef

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 16:78–82CrossRef

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 42:53–61CrossRefPubMed

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 23:1553–1558CrossRefPubMed

Title: Restorative potentiality of S-allylcysteine against diabetic nephropathy through attenuation of oxidative stress and inflammation in streptozotocin–nicotinamide-induced diabetic rats
Authors: V. V. Sathibabu Uddandrao
Parim Brahmanaidu
Ramavat Ravindarnaik
Pothani Suresh
S. Vadivukkarasi
Ganapathy Saravanan
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 6/2019
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-018-1795-x

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Aim

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aim

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2019

Differences in the dietary requirement for vitamin D among Caucasian and East African women at Northern latitude

High intake of dietary fibre from fruit and vegetables reduces the risk of hospitalisation for diverticular disease

Significant metabolic improvement by a water extract of olives: animal and human evidence

Metabolite profiles evaluated, according to sex, do not predict resting energy expenditure and lean body mass in healthy non-obese subjects

Effect of macronutrient composition on meal-induced thermogenesis in adolescents with obesity

Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page