Restorative potentiality of S-allylcysteine against diabetic nephropathy through attenuation of oxidative stress and inflammation in streptozotocin–nicotinamide-induced diabetic rats
- 187 Downloads
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.
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.
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.
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.
KeywordsNephropathy Oxidative stress Natural products Metabolic disorders Anti-diabetic
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.
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.
- 1.Tesfaye S, Gill G (2011) Chronic diabetic complications in Africa. Afr J Diabetes Med. 19:4–8Google Scholar
- 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 66:245–253CrossRefGoogle Scholar
- 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 48:800–810Google Scholar
- 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.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
- 20.Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 21:130–132Google Scholar
- 22.Paglia D, Valentine W (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169Google Scholar
- 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
- 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
- 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
- 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.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 27:1474–1480Google Scholar
- 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 1812:719–731Google Scholar
- 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 442:143–154CrossRefGoogle Scholar
- 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 113:1200–1204Google Scholar