title: Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats.
abstract: The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Bogdan
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Isabela
authors.initials: I
authors.lastname: Silosi
authors.affiliation: Department of Periodontology, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Petra
authors.initials: P
authors.lastname: Surlin
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Andrei Adrian
authors.initials: AA
authors.lastname: Tica
authors.affiliation: Department of Obstetrics-Gynecology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Oana Sorina
authors.initials: OS
authors.lastname: Tica
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Tudor-Adrian
authors.initials: TA
authors.lastname: Balseanu
authors.affiliation: Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Romania.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Rauten
authors.affiliation: Department of Dentoalveolar Surgery, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street, 200349 Craiova, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Camen
keywords: Aripiprazole; L-FABP/FABP1; RGM-C/HJV; TNF-α; hepatotoxicity; lipid metabolism disorders; mirtazapine; weight gain