title: Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).
abstract: BACKGROUND
  Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM.
  
  
  METHODS
  After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls.
  
  
  RESULTS
  Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups.
  
  
  CONCLUSIONS
  eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Medicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Dain
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Medicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.|Cátedra de Histología, Embriología y Genética, Universidad Nacional de La Rioja, La Rioja, Argentina.|CONICET, Córdoba, Argentina.
authors.forename: Gaston
authors.initials: G
authors.lastname: Repossi
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Medicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina.
authors.forename: Gustavo T
authors.initials: GT
authors.lastname: Diaz-Gerevini
authors.affiliation: Department of Food Science, Penn State University, 326 Food Science Building, University Park, PA, 16802, USA.
authors.forename: Jairam
authors.initials: J
authors.lastname: Vanamala
authors.affiliation: UND Life Sciences, 2020 S 360th St, # K-202, Federal Way, WA, 98003, USA. Undurti@hotmail.com.|BioScience Research Centre and Department of Medicine, GVP Hospital, Gayatri Vidya Parishad College of Engineering Campus, Visakhapatnam, 530 048, India. Undurti@hotmail.com.
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
authors.affiliation: Biología Celular, Histología y Embriología, Facultad de Ciencias Medicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba, Argentina. aeynard@gmail.com.|CONICET, Córdoba, Argentina. aeynard@gmail.com.
authors.forename: Aldo R
authors.initials: AR
authors.lastname: Eynard
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000032:analysis; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D016718:Arachidonic Acid; D015415:Biomarkers; D002097:C-Reactive Protein; D015525:Fatty Acids, Omega-3; D006442:Glycated Hemoglobin; D015850:Interleukin-6; D009637:Masoprocol; D014280:Triglycerides; D005723:gamma-Glutamyltransferase
keywords: Chronic inflammation; Nordihydroguaiaretic acid; Oxidation process; PUFAs; Plasma triglycerides; Type 2 diabetes; eSS rats (Stillman Salgado rats)