title: Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes.
abstract: BACKGROUND
  Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart.
  
  
  METHODS
  Rats with developed hyperglycemia after STZ injection were divided into two groups; diabetic (Dia) and diabetic+garlic (Dia+Garl). Garlic was administered at a dose of 250mg/kg/day, orally for four weeks. An additional group was maintained to evaluate the effect of raw garlic administration on control rat heart.
  
  
  RESULTS
  We have observed altered functioning of cardiac mitochondrial enzymes involved in metabolic pathways, and increased levels of cardiac ROS with decreased activity of catalase and SOD in diabetic rats. Cardiac mRNA expression of TFAM, PGC-1α, and CO1 was also altered in diabetes. In addition, reduced levels of electron transport chain complexes that observed in Dia group were normalized with garlic administration. This indicates the presence of increased oxidative stress with mitochondrial dysfunctioning in diabetic heart. We have observed reduced activity of SIRT3 and increased acetylation of MnSOD. Silencing SIRT-3 in cells also revealed the same. However, administration of garlic improved the SIRT-3 and MnSOD activity, by deacetylating MnSOD. Increased SOD activity was correlated with reduced levels of ROS in garlic-administered rat hearts.
  
  
  CONCLUSIONS
  Collectively, our results provide an insight into garlic's protection to T1DM heart through activation of SIRT3-MnSOD pathway.
authors: Department of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: mdsultana@gmail.com.
authors: Md Razia
authors: MR
authors: Sultana
authors: Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute, Faridabad 122001, Haryana, India. Electronic address: pankajbagul2787@gmail.com.
authors: Pankaj K
authors: PK
authors: Bagul
authors: Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute, Faridabad 122001, Haryana, India. Electronic address: pbkatare@gmail.com.
authors: Parameshwar B
authors: PB
authors: Katare
authors: Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute, Faridabad 122001, Haryana, India. Electronic address: sohebmsa@gmail.com.
authors: Soheb
authors: S
authors: Anwar Mohammed
authors: Department of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: rajpadiya@gmail.com.
authors: Raju
authors: R
authors: Padiya
authors: Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute, Faridabad 122001, Haryana, India. Electronic address: skbanerjee@thsti.res.in.
authors: Sanjay K
authors: SK
authors: Banerjee
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy*; D005737:Garlic; D006321:Heart / Q000502:physiology; D015151:Immunoblotting; D008929:Mitochondria, Heart / Q000201:enzymology / Q000473:pathology; D009842:Oligopeptides / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: C408902:MHC binding peptide; D009842:Oligopeptides; C000607791:SIRT3 protein, rat; D003094:Collagen; D037761:Sirtuins
keywords: Acetylation; Diabetic cardiomyopathy; Garlic; Mitochondria; MnSOD; SIRT3; Sirtuins