Oxidative Modification in the Salivary Glands of High Fat-Diet Induced Insulin Resistant Rats

Still little is known about the role of oxidative stress (OS) in the pathogenesis of the salivary gland dysfunction in the course of insulin resistance (IR). To induce IR rats was fed with a high fat diet (HFD) during 8 weeks. Stimulated and non-stimulated salivary flow rate, total protein, as well as oxidative damage markers: 4-HNE protein adduct, 8-isoprostanes (8-isoP), 8-hydroxy-D-guanosine (8-OHdG), advanced oxidation protein product (AOPP), and protein carbonyls (PC) were determined in the plasma and submandibular and parotid glands of IR and control rats. We have shown a significant decrease (45%) of the stimulated salivary flow rate, and in the total protein concentration in the parotid (35%) and submandibular (10%) glands of HFD IR as compared to the control rats. The level of 4-HNE protein adduct (15%) and 8-isoP (20%) in the submandibular glands of IR rats as well as total level of 4-HNE protein adduct (39%), 8-isoP (27%), AOPP (25%), PC (32%), and 8-OHdG (18%) in the parotid glands of IR rats were significantly higher as compared to the control group. We showed no correlation between the assessed OS parameters in the plasma and salivary glands. However, the redox balance in both glands shifted toward the oxidative status, parotid glands of IR rats are exposed to greater intensity OS. Stimulated secretory ability and mechanisms involved in the synthesis/secretion of proteins in the salivary glands are depressed in the course of IR. Oxidative damage in the salivary glands arises independently from the general OS in the course of insulin resistance induced by a high fat diet.

[1]  Antonio Ayala,et al.  Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal , 2014, Oxidative medicine and cellular longevity.

[2]  E. Benjamin,et al.  Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[3]  B. Avcı,et al.  Glutathione levels in plasma, saliva and gingival crevicular fluid after periodontal therapy in obese and normal weight individuals. , 2016, Journal of periodontal research.

[4]  O. Erel,et al.  A new automated colorimetric method for measuring total oxidant status. , 2005, Clinical biochemistry.

[5]  G. Farronato,et al.  Correlation between salivary and serum oxidized LDL levels: a pilot study on overweight/obese subjects. , 2015, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[6]  O. O. Erejuwa.  Oxidative Stress in Diabetes Mellitus: Is There a Role for Hypoglycemic Drugs and/or Antioxidants? , 2012 .

[7]  K. Zwierz,et al.  Salivary innate defense system in type 1 diabetes mellitus in children with mixed and permanent dentition , 2013, Acta odontologica Scandinavica.

[8]  J. Nicolau,et al.  Antioxidant parameters and lipid peroxidation in salivary glands of streptozotocin-induced diabetic rats. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[9]  F. Tinahones,et al.  Oxidative Stress in Severely Obese Persons Is Greater in Those With Insulin Resistance , 2009, Obesity.

[10]  L. Packer,et al.  Oxidative damage to proteins: spectrophotometric method for carbonyl assay. , 1994, Methods in enzymology.

[11]  R. Nagler,et al.  Salivary analysis in oral cancer patients , 2007, Cancer.

[12]  David A. Bernlohr,et al.  Carbonylation of Adipose Proteins in Obesity and Insulin Resistance , 2007, Molecular & Cellular Proteomics.

[13]  M. Karin,et al.  JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  S. Udenfriend,et al.  Spontaneously hypertensive rat. , 1972, Science.

[15]  Chunyan Zhu,et al.  Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats. , 2013, World journal of gastroenterology.

[16]  V. Lushchak.  Classification of oxidative stress based on its intensity , 2014, EXCLI journal.

[17]  Roger Davis,et al.  The c-Jun NH2-terminal Kinase Promotes Insulin Resistance during Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307 * , 2000, The Journal of Biological Chemistry.

[18]  Michael Karin,et al.  Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases , 2005, Cell.

[19]  M. Żendzian-Piotrowska,et al.  Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands , 2016, Journal of diabetes research.

[20]  Morihiro Matsuda,et al.  Increased oxidative stress in obesity and its impact on metabolic syndrome. , 2004, The Journal of clinical investigation.

[21]  K. T. Sassaki,et al.  Spontaneously hypertensive rat as experimental model of salivary hypofunction. , 2012, Archives of oral biology.

[22]  S. Sierakowski,et al.  Salivary antioxidants in patients with systemic sclerosis. , 2014, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[23]  L. Wojtczak,et al.  Acyl-CoA-induced generation of reactive oxygen species in mitochondrial preparations is due to the presence of peroxisomes. , 2009, Free radical biology & medicine.

[24]  M. Lovell,et al.  Oxidatively modified nucleic acids in preclinical Alzheimer's disease (PCAD) brain , 2011, Mechanisms of Ageing and Development.

[25]  M. Okamoto,et al.  Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats , 2013, Diabetology & Metabolic Syndrome.

[26]  A. Paes,et al.  Duodenal jejunal bypass attenuates non-alcoholic fatty liver disease in western diet-obese rats. , 2014, Acta cirurgica brasileira.

[27]  Omer Kalayci,et al.  Oxidative Stress and Antioxidant Defense , 2012, The World Allergy Organization journal.

[28]  F. Milagro,et al.  Weight Gain Induced by High‐Fat Feeding Involves Increased Liver Oxidative Stress , 2006, Obesity.

[29]  G. Pendyala,et al.  Evaluation of Total Antioxidant Capacity of Saliva in Type 2 Diabetic Patients with and without Periodontal Disease: A Case-Control Study , 2013, North American journal of medical sciences.

[30]  M. Kawaguchi,et al.  Lowered susceptibility of muscarinic receptor involved in salivary secretion of streptozotocin-induced diabetic rats. , 2001, Japanese journal of pharmacology.

[31]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[32]  M. Żendzian-Piotrowska,et al.  Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands , 2016, Journal of diabetes research.

[33]  I. Morales-Bozo,et al.  Salivary gland dysfunction markers in type 2 diabetes mellitus patients , 2015, Journal of clinical and experimental dentistry.

[34]  E. Stadtman,et al.  Free radical-mediated oxidation of free amino acids and amino acid residues in proteins , 2003, Amino Acids.

[35]  T Zima,et al.  Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. , 2002, Physiological research.

[36]  H. Car,et al.  Antioxidant profile of salivary glands in high fat diet-induced insulin resistance rats. , 2014, Oral diseases.

[37]  M. Abdollahi,et al.  Oxidative stress status and DNA damage in saliva of human subjects with oral lichen planus and oral squamous cell carcinoma. , 2012, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[38]  F. Espíndola,et al.  Alterations of antioxidant biomarkers and type I collagen deposition in the parotid gland of streptozotocin-induced diabetic rats. , 2011, Archives of oral biology.

[39]  Brigitte I Frohnert,et al.  Increased Adipose Protein Carbonylation in Human Obesity , 2011, Obesity.

[40]  M. Żendzian-Piotrowska,et al.  Impact of morbid obesity and bariatric surgery on antioxidant/oxidant balance of the unstimulated and stimulated human saliva. , 2016, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[41]  H. Car,et al.  Antioxidant profile, carbonyl and lipid oxidation markers in the parotid and submandibular glands of rats in different periods of streptozotocin induced diabetes. , 2015, Archives of oral biology.

[42]  N. Al-Rawi.  Oxidative stress, antioxidant status and lipid profile in the saliva of type 2 diabetics , 2011, Diabetes & vascular disease research.

[43]  NarotzkiBaruch,et al.  Enhanced Cardiovascular Risk and Altered Oxidative Status in Elders with Moderate Excessive Body Fat , 2014 .

[44]  F. N. Nogueira,et al.  Sialic acid reduction in the saliva of streptozotocin induced diabetic rats. , 2012, Archives of oral biology.

[45]  C. Carda,et al.  Structural and functional salivary disorders in type 2 diabetic patients. , 2006, Medicina oral, patologia oral y cirugia bucal.

[46]  A. Bozzato,et al.  Salivary gland biometry in female patients with eating disorders , 2008, European Archives of Oto-Rhino-Laryngology.