title: Anti-fibrotic cardio protective efficacy of aminoguanidine against streptozotocin induced cardiac fibrosis and high glucose induced collagen up regulation in cardiac fibroblasts.
abstract: This study mainly focuses on cardio protective anti-fibrotic activity of aminoguanidine against streptozotocin induced cardiac fibrosis and high glucose induced collagen accumulation in cardiac fibroblasts. Dysregulation of matrix metalloproteinase especially 2 and 9 were considered to be responsible for the abnormal collagen deposition, which resulting improper cardiac contractile function in diabetic mice. Mice received a single dose of streptozotocin (100 mg/kg) through tail vein to induce diabetes. Normal and diabetic mice received aminoguanidine orally (100 mg/kg/day) throughout the study period of 8 weeks. Cardiac fibroblasts cultured and exposed to high glucose, aminoguanidine and both for 48 h. Collagen quantitatively estimated in both in vivo and in vitro models. Altered structural changes were studied using the Masson tri-chrome staining, TEM images of cardiac sections. Increased collagen and metalloproteinase activities were confirmed using gelatin zymography, western blotting and gene expression studies. The exact mechanism responsible for high glucose induced collagen up regulation in diabetic heart was incompletely understood. From this above in vivo and in vitro results, we conclude that, the cardio protective anti fibrotic activity of amino guanidine was mainly attributed by exhibiting the inhibitory efficacy against streptozotocin and high glucose induced collagen accumulation probably by inhibiting high glucose altered metalloproteinase-2 and -9 activities.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India. ganm.u.research@gmail.com
authors.forename: Gangadhara Prasadachari
authors.initials: GP
authors.lastname: Vadla
authors.forename: Elangovan
authors.initials: E
authors.lastname: Vellaichamy
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005355:Fibrosis / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009206:Myocardium / Q000473:pathology*; D013311:Streptozocin / Q000633:toxicity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D015854:Up-Regulation; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D002316:Cardiotonic Agents; D003094:Collagen; D005947:Glucose; D006146:Guanidines; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013311:Streptozocin; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C004479:pimagedine