Switching to normal diet reverses kwashiorkor-induced salivary impairments via increased nitric oxide level and expression of aquaporin 5 in the submandibular glands of male Wistar rats.

Kwashiorkor, a form of malnutrition, has been shown to cause impaired salivary secretion. However, there is dearth of information on the mechanism that underlies this complication. Also, whether returning to normal diet after kwashiorkor will reverse these complications or not is yet to be discerned. Thus, this study aimed at assessing the mechanisms that underlie kwashiorkor-induced salivary impairments and to evaluate the effects of switching back to normal-diet on kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into 3 groups (control group, kwashiorkor group (KG), re-fed kwashiorkor group (RKG)) of 7 rats each. The control group had standard rat chow while the KG and RKG were fed 2% protein diet for 6 weeks to induce kwashiorkor. The RKG had their diet changed to standard rat-chow for another 6 weeks. Blood and stimulated saliva samples were collected for the analysis of total protein, electrolytes, amylase, immunoglobulin A (IgA) secretion rate, leptin, and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor, and aquaporin 5 in the submandibular glands were also determined. Data were presented as means ± SEM and compared using ANOVA with Tukey's post hoc test. RKG showed improved salivary function evidenced by reduced salivary lag-time and potassium and increased flow rate, sodium, amylase, IgA secretion rate, leptin, submandibular nitric oxide level, and aquaporin 5 expression compared with KG. This study for the first time demonstrated that kwashiorkor caused significant reduction in salivary secretion through reduction of nitric oxide level and aquaporin 5 expression in submandibular salivary glands. Normal-diet re-feeding after kwashiorkor returned salivary secretion to normal.

[1]  H. Xu,et al.  Pre- and Post-synaptic Effects of Botulinum Toxin A on Submandibular Glands , 2015, Journal of dental research.

[2]  Lei Wang,et al.  Effect of Phenylephrine Pretreatment on the Expressions of Aquaporin 5 and c-Jun N-Terminal Kinase in Irradiated Submandibular Gland , 2015, Radiation research.

[3]  Yu-xiong Su,et al.  Reinnervated nerves contribute to the secretion function and regeneration of denervated submandibular glands in rabbits. , 2014, European journal of oral sciences.

[4]  T. Yamamura,et al.  Epiregulin is critical for the acinar cell regeneration of the submandibular gland in a mouse duct ligation model. , 2014, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[5]  K. Takata,et al.  Effects of Repeated Administration of Pilocarpine and Isoproterenol on Aquaporin-5 Expression in Rat Salivary Glands , 2013, Acta histochemica et cytochemica.

[6]  Young-Mo Kim,et al.  Analysis of age-related changes in the functional morphologies of salivary glands in mice. , 2013, Archives of oral biology.

[7]  A. Soliman,et al.  Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children , 2012, Indian journal of endocrinology and metabolism.

[8]  T. Kawai,et al.  Expression and Possible Immune-regulatory Function of Ghrelin in Oral Epithelium , 2011, Journal of dental research.

[9]  M. Gleeson,et al.  Acute and chronic effects of exercise on markers of mucosal immunity. , 2009, Frontiers in bioscience.

[10]  J. E. Melvin,et al.  The salivary gland fluid secretion mechanism. , 2009, The journal of medical investigation : JMI.

[11]  R. Katz,et al.  Effect of childhood malnutrition on salivary flow and pH. , 2008, Archives of oral biology.

[12]  Patrícia Del Vigna de Almeida,et al.  Saliva composition and functions: a comprehensive review. , 2008, The journal of contemporary dental practice.

[13]  G. Carpenter,et al.  Regulation of salivary gland function by autonomic nerves , 2007, Autonomic Neuroscience.

[14]  C. Delporte,et al.  Distribution and roles of aquaporins in salivary glands. , 2006, Biochimica et biophysica acta.

[15]  M. Vatta,et al.  Protein free diet feeding: effects on sympathetic activity and salivary evoked secretion in the submandibular gland of the rat. , 2006, Archives of oral biology.

[16]  M. Rauh,et al.  Identification of ghrelin in human saliva: production by the salivary glands and potential role in proliferation of oral keratinocytes. , 2005, Clinical chemistry.

[17]  M. Abdollahi,et al.  On the relation of nitric oxide to nifedipine‐induced gingival hyperplasia and impaired submandibular glands function in rats in vivo , 2005, Fundamental & clinical pharmacology.

[18]  J. Kamau,et al.  Defects in resting metabolic rates and mitochondrial respiration in Kwashiorkor and dietary obese rats , 1991, Journal of Comparative Physiology B.

[19]  T. Domon,et al.  Cell death and cell proliferation in the regeneration of atrophied rat submandibular glands after duct ligation. , 2004, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[20]  M. Rauh,et al.  Differential distribution and expression of leptin and the functional leptin receptor in major salivary glands of humans. , 2003, The Journal of endocrinology.

[21]  Y. Ishikawa,et al.  Age-related Decreases in the Response of Aquaporin-5 to Acetylcholine in Rat Parotid Glands , 2003, Journal of dental research.

[22]  Herbert Herzog,et al.  Hypothalamic regulation of energy homeostasis. , 2002, Best practice & research. Clinical endocrinology & metabolism.

[23]  C. Yao,et al.  Divergent expression and localization of aquaporin 5, an exocrine-type water channel, in the submandibular gland of Sprague-Dawley rats , 2002, Pflügers Archiv.

[24]  Y. Ishikawa,et al.  The muscarinic acetylcholine receptor-stimulated increase in aquaporin-5 levels in the apical plasma membrane in rat parotid acinar cells is coupled with activation of nitric oxide/cGMP signal transduction. , 2002, Molecular pharmacology.

[25]  M. Rauh,et al.  Identification of leptin in human saliva. , 2001, The Journal of clinical endocrinology and metabolism.

[26]  M. Abdollahi,et al.  Alteration by cadmium of rat submandibular gland secretory function and the role of the l-arginine/nitric oxide pathway. , 2000, Pharmacological research.

[27]  M. Skowroński,et al.  alpha(1)-adrenoceptor-induced trafficking of aquaporin-5 to the apical plasma membrane of rat parotid cells. , 1999, Biochemical and biophysical research communications.

[28]  B. Baum,et al.  Receptors in Salivary Glands , 1999 .

[29]  K. Takata,et al.  Aquaporin-5 (AQP5), a water channel protein, in the rat salivary and lacrimal glands: immunolocalization and effect of secretory stimulation , 1999, Cell and Tissue Research.

[30]  A. Lomniczi,et al.  Role of Nitric Oxide in Salivary Secretion , 1998, Neuroimmunomodulation.

[31]  J. R. Garrett,et al.  Neural regulation of blood flow in the rat submandibular gland. , 1998, European journal of morphology.

[32]  I. Dardick,et al.  Cell population changes during atrophy and regeneration of rat parotid gland. , 1998, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[33]  M. Skowroński,et al.  Acetylcholine acts on M3 muscarinic receptors and induces the translocation of aquaporin5 water channel via cytosolic Ca2+ elevation in rat parotid glands. , 1998, Biochemical and biophysical research communications.

[34]  E. Clementi,et al.  Nitric oxide modulation of agonist-evoked intracellular Ca2+ release in neurosecretory PC-12 cells: inhibition of phospholipase C activity via cyclic GMP-dependent protein kinase I. , 1995, Molecular Pharmacology.

[35]  M. Lenander-Lumikari,et al.  Saliva Composition in Indian Children with Chronic Protein-Energy Malnutrition , 1994, Journal of dental research.

[36]  I. Johansson,et al.  The Effect of Malnutrition on Caries Development and Saliva Composition in the Rat , 1985, Journal of dental research.

[37]  R. Watson,et al.  Effect of moderate chronic protein deficiency on rat salivary components. , 1980, Journal of NutriLife.

[38]  C. Dawes Effects of Diet on Salivary Secretion and Composition , 1970, Journal of dental research.

[39]  L. Sreebny,et al.  Effect of food consistency and decreased food intake on rat parotid and pancreas. , 1968, The American journal of physiology.

[40]  C. Schneyer,et al.  Salivary Gland Atrophy in Rat Induced by Liquid Diet.∗ , 1964, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.