title: All-Trans Retinoic Acid supplementation prevents cardiac fibrosis and cytokines induced by Methylglyoxal.
abstract: Methylglyoxal (MG), a metabolic intermediate of glycolysis is a precursor for endogeneous production of advanced glycation end-products. The increased production of MG have negative influence over the structure and function of different biomolecules and thus plays an important role in the pathogenesis of diabetic cardiac complications. Retinoic acid (RA), an active metabolite of vitamin A, has a major role in preventing cardiac remodeling and ventricular fibrosis. Hence, the objective of the present study was to determine whether rats administered with all-trans retinoic acid (RA) could attenuate MG induced pathological effects. Wistar rats were divided into 4 groups. Group 1 rats were kept as control; Group 2 rats were administrated with MG (75 mg/kg/day) for 8 weeks. Group 3 rats were given RA (Orally, 1.0 mg/kg/day) along with MG; Group 4 rats received RA alone. Cardiac antioxidant status, induction of fibrosis, AGE receptor (RAGE) and cytokines expression was evaluated in the heart tissues. Administration of MG led to depletion of antioxidant enzymes, induction of fibrosis (p < 0.001), up-regulated expression of RAGE (3.5 fold), TGF-β (4.4 fold), SMAD2 (3.7 fold), SMAD3 (6.0 fold), IL-6 (4.3 fold) and TNF-α (5.5 fold) in the heart tissues compared to control rats. Moreover, the exogenous administration of MG caused significant (p < 0.001) increase in the circulating CML levels. Whereas, RA treatment prevented the induction of fibrosis and restored the levels of cytokines and RAGE expression. Methylglyoxal-induced fibrosis can lead to pathological effects in the heart tissues. RA attenuates the effects of MG in the heart, suggesting that it can be of added value to usual diabetic therapy.
authors.affiliation: Department of Biotechnology, School of Chemical & Biotechnology, SASTRA University, Thanjavur, 613 401, Tamil Nadu, India. spumadevi@gmail.com.
authors.forename: Umadevi
authors.initials: U
authors.lastname: Subramanian
authors.affiliation: Department of Biotechnology, School of Chemical & Biotechnology, SASTRA University, Thanjavur, 613 401, Tamil Nadu, India.
authors.forename: Devipriya
authors.initials: D
authors.lastname: Nagarajan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D019587:Dietary Supplements; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis; D051899:Smad2 Protein / Q000096:biosynthesis; D051900:Smad3 Protein / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D018754:Ventricular Dysfunction / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: C000593874:Ager protein, rat; D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D014212:Tretinoin; D011765:Pyruvaldehyde
keywords: Advanced glycation end products; All-trans retinoic acid; Cardiac fibrosis; Diabetes; Methylglyoxal