Fatty acids rehabilitated long-term neurodegenerative-like symptoms in olfactory bulbectomized rats

A deficit/hyperactivity disorder (ADHD) is among the most frequent neurodevelopmental disorders. Atomoxetine (ATX) and methylphenidate (MPH) have been recommended as primary medication choices to treat inhibitionand attention-related dysfunctions in ADHD children. This study used functional near-infrared spectroscopy (fNIRS) to explore the efficacy of both medications in school-aged children with ADHD for inhibitory and attention task performance. fNIRS is a promising tool, offering robust advantages such as its compactness, affordable price, tolerance to body motion and accessibility. We monitored the oxy-hemoglobin changes in ADHD children (6 to 14 years old) during go/nogo or oddball tasks before and 1.5 h after ATX, MPH or placebo administration, in a randomized, double-blind, placebo-controlled experiment. Age-, genderand IQ-matched healthy controls, who did not receive medications or a placebo, were also monitored. In the control subjects, the go/nogo task modulated the right inferior and middle prefrontal gyri (IFG/MFG) and the oddball task modulated the right IFG/MFG and inferior parietal cortex (IPL). In ADHD children, these activations were absent in pre-medicated conditions. The reduction in the right IFG/MFG activation was normalized by both ATX and MPH for go/nogo and oddball tasks, but the right IPL was normalized only by ATX in the oddball task. These results led us to conclude that fNIRS could visualize the differential neuropharmacological effects of both substances in the inhibitory and attentional networks: ATX to up-regulate the noradrenergic system reflected in the right IFG/MFG and IPL activations, and MPH to up-regulate the dopamine system reflected in the IFG/MFG activations.

[1]  J. Cortés-Eslava,et al.  Evaluation of the genotoxic potential of dimethyl sulfoxide (DMSO) in meristematic cells of the root of Vicia faba , 2012, Toxicology and Environmental Health Sciences.

[2]  Ryoichi Fujiwara,et al.  Toxicological Evaluation of Acyl Glucuronides of Nonsteroidal Anti-Inflammatory Drugs Using Human Embryonic Kidney 293 Cells Stably Expressing Human UDP-Glucuronosyltransferase and Human Hepatocytes , 2011, Drug Metabolism and Disposition.

[3]  M. Parolini,et al.  An in vitro biomarker approach for the evaluation of the ecotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs). , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[4]  S. Alahuhta,et al.  Effects of combination treatment with ketoprofen 100 mg + acetaminophen 1000 mg on postoperative dental pain: a single-dose, 10-hour, randomized, double-blind, active- and placebo-controlled clinical trial. , 2009, Clinical therapeutics.

[5]  M. Hacımustafaoğlu,et al.  Antipyretic effect of ketoprofen , 2009, Indian journal of pediatrics.

[6]  H. Mizu,et al.  Intra-articular penetration of ketoprofen and analgesic effects after topical patch application in rats. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[7]  H. Çelik,et al.  Lymphocyte DNA damage and total antioxidant status in patients with white-coat hypertension and sustained hypertension. , 2008, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[8]  Yong Zhao,et al.  The immunity of splenic and peritoneal F4/80+ resident macrophages in mouse mixed allogeneic chimeras , 2007, Journal of Molecular Medicine.

[9]  K. Lam,et al.  Combining the rapid MTT formazan exocytosis assay and the MC65 protection assay led to the discovery of carbazole analogs as small molecule inhibitors of Aβ oligomer-induced cytotoxicity , 2007, Brain Research.

[10]  J. Weekley,et al.  Bioactivation of carboxylic acid compounds by UDP-Glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity. , 2006, Chemical research in toxicology.

[11]  R. Breyer,et al.  Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. , 2004, Pharmacology & therapeutics.

[12]  J. Błasiak,et al.  In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues. , 1999, Mutation research.

[13]  B. Milpied,et al.  Kétoprofène gel et effets secondaires cutanés: bilan d'une enquête sur 337 notifications. , 1998 .

[14]  P. Olive,et al.  The comet assay: a comprehensive review. , 1995, Mutation research.

[15]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[16]  K J Johanson,et al.  Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. , 1984, Biochemical and biophysical research communications.

[17]  M. Ashraf,et al.  Assessment of the cytotoxic and anti-viral potential of aqueous extracts from different parts of Acacia nilotica (Linn) Delile against Peste des petits ruminants virus. , 2013, Environmental toxicology and pharmacology.

[18]  Jacqueline Cloos,et al.  Cell sensitivity assays: the MTT assay. , 2011, Methods in molecular biology.

[19]  M. Yam,et al.  Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters nanoemulsion. , 2010, Journal of oleo science.

[20]  E. De Clercq,et al.  The novel phosphoramidate derivatives of NSAID 3-hydroxypropylamides: synthesis, cytostatic and antiviral activity evaluations. , 2009, European journal of medicinal chemistry.

[21]  M. Triggiani,et al.  Severe oral symptoms after the use of an oral solution containing ketoprofen in two NSAIDs-sensitive patients. , 2003, Journal of investigational allergology & clinical immunology.

[22]  J. Plumb Cell sensitivity assays : the MTT assay. , 1999, Methods in molecular medicine.