http://informahealthcare.com/txm ISSN: 1537-6516 (print), 1537-6524 (electronic) Toxicol Mech Methods, Early Online: 1–7 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15376516.2014.961216 RESEARCH ARTICLE Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice Jadiswami C 1 , Megha H. M 1 , Shivsharan B. Dhadde 1 , Sharanbasappa Durg 1 , Pandharinath P. Potadar 2 , Thippeswamy B. S. 1 *, and Veerapur V. P. 1 1 Sree Siddaganga College of Pharmacy, Tumkur, Karnataka, India and 2 BLDEA’s College of Pharmacy, Bijapur, Karnataka, India Abstract 3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington’s disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions. Keywords Antioxidant, COX inhibitor, Huntington’s disease, oxicam History Received 22 June 2014 Revised 2 August 2014 Accepted 31 August 2014 Published online 24 September 2014 Introduction Huntington’s disease (HD) is an incurable neuropsychiatric disease characterized by degeneration of basal ganglia, associated to impaired cognition, motor abnormalities and emotional disturbance (Cowan & Raymond, 2006). HD patients often exhibit deficits in executive tasks requiring planning, cognitive flexibility and problem solving. Due to its complexity and unpredictability, HD poses challenges for health care professionals (Shivasharan et al., 2013). Earlier report reveals, excitotoxicity, oxidative stress, alter- ations in energy metabolism and mitochondrial dysfunction are involved in the pathophysiology of HD (Kumar et al., 2007). The molecular pathology of HD is expansion of the CAG trinucleotide in the first exon of a gene on chromosome four. The CAG repeats are translated to polyglutamine repeats in the expressed protein, huntingtin (Walling et al., 1998). Polyglutamine expansion modifies many of protein interactions with huntingtin and leads to its aggregation and the formation of neuronal nuclear inclusions which ultimately concludes in cell death (Walling et al., 1998). 3-Nitropropionic acid (3-NP)-induced neurotoxicity is a well-known chemical-induced experimental model to study the pathogenesis of HD. 3-NP (fungal toxin) produces HD-like symptoms in both animals and humans (Ludolph et al., 1991). In addition, 3-NP produces brain lesions specifically in the striatum, besides the hippocampus, thalamus and brain cortex areas are also affected (Beal et al., 1993; Brouillet et al., 1999). 3-NP crosses the blood– brain barrier, and irreversibly inhibits the electron-transport enzyme succinate dehydrogenase (SDH). Subsequently, it blocks the transport of electrons in oxidative phosphorylation, causing decreased adenosine triphosphate (ATP) levels in brain, which plays a central role in 3-NP toxicity. Neurons are metabolically very active cells; hence, process affecting mitochondrial function invariably leads to neuronal death (Tunez et al., 2008). It is well-reported that 3-NP produces free radicals and consequent disturb of glutathione (GSH) redox cycle (Kumar & Kumar, 2008). Increased oxidative stress activates the apoptotic and neuroinflammatory pro- cesses, which triggers neuronal degeneration (Liot et al., 2009). Neuroinflammation is a key event involved in the *Present address: Department of Biomedical Science, College of Pharmacy, Shaqra University, Al-Dawadmi, Kingdom of Saudi Arabia. Address for correspondence: Mr Shivsharan B. Dhadde, M Pharm, Department of Pharmacology, Sree Siddaganga College of Pharmacy, B. H. Road, Tumkur, Karnataka 572 102, India. Tel: +918123508881. E-mail: sharanapharma@hotmail.com