Huntington's disease is a progressive, degenerative disease characterized by abnormal body movements called chorea, and a reduction of various mental abilities. 3-Nitropropionic acid, an inhibitor of complex II of the electron transport chain, causes Huntington's disease-like symptoms in rodents. Recently, it has been reported that oxidative stress, which is one of the pathological hallmarks of various neurodegenerative disorders, also plays an important role in the pathogenesis of Huntington's disease. The present study was designed to investigate effects of resveratrol, an antioxidant with cyclooxygenase I inhibitory activity, in the 3-nitropropionic acid-induced model of Huntington's disease. Intraperitoneal administration of 3-nitropropionic acid (20 mg/kg for 4 days) caused significant loss of body weight, a decline in motor function (locomotor activity, movement pattern and vacuous chewing movements) and poor retention of memory. Repeated treatment with resveratrol (5 and 10 mg/kg, orally), once daily for a period of 8 days beginning 4 days prior to 3-nitropropionic acid administration, significantly improved the 3-nitropropionic acid-induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-nitropropionic acid administration significantly increased lipid peroxidation, nitrite levels, and depleted reduced glutathione levels, and decreased succinate dehydrogenase activity in the brains of rats. The results of the present study indicate that resveratrol (5 and 10 mg/kg, orally) significantly reversed 3-nitropropionic acid-induced motor and cognitive impairment, and that the beneficial effects of resveratrol might be attributed to its antioxidant activity.

Systemic administration of 3-nitropropionic acid (3-NP), a complex II inhibitor of the electron transport chain, causes motor and cognitive deficits that are associated with excitotoxicity and excessive free radical generation. Recently, cyclooxygenase (COX) inhibitors have been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate the effects of COX inhibitors in 3-NP-induced cognitive impairment and oxidative stress in rats. Intraperitoneal administration of 3-NP (20 mg/kg for 4 days) showed motor abnormalities and cognitive impairment in rats. Chronic treatment with naproxen (10 and 20 mg/kg) and valdecoxib (5 and 10 mg/kg) once daily for a period of 8 days beginning 4 days prior to 3-NP administration significantly improved 3-NP-induced motor and cognitive impairment in rats. Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and nitrite levels, depleted reduced glutathione levels and reduced succinate dehydrogenase (SDH) activity in the brains of rats, whereas administration of naproxen, a nonselective COX inhibitor (10 and 20 mg/kg p.o.) and valdecoxib, a selective COX-2 inhibitor (5 and 10 mg/kg p.o.) significantly attenuated 3-NP-induced oxidative stress. Cyclooxygenase inhibitors also significantly restored the decreased SDH activity. The results of the present study clearly indicate that naproxen and valdecoxib showed protection against 3-NP-induced motor and cognitive impairment by decreasing oxidative stress.

This study was designed to investigate the protective effects of curcumin against colchicine-induced cognitive impairment and oxidative stress in rats. Male Wistar rats (weighing 150-200 g) received colchicine intracerebroventricularly (15 microg per rat), and cognitive dysfunctions were evaluated by the Morris water maze and the plus maze performance task and supported by biochemical tests. Central administration of colchicine caused memory deficit in both the Morris water maze and the elevated plus maze task paradigm tasks. Chronic treatment with curcumin (5-50 mg/kg, p.o.) twice daily for a period of 25 days beginning 4 days prior to colchicine injection significantly improved the colchicine-induced cognitive impairment. Biochemically, chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the decreased reduced glutathione level and acetylcholinesterase activity, and attenuated the raised colchicine-induced elevated nitrite levels. The results of the present study indicate that curcumin has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.

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The systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) which act by inhibiting cyclooxygenase (COX) is severely hampered by gastric and peptic ulcers. The topical delivery of NSAIDs has the advantages of avoiding gastric and peptic ulcers and delivering the drug to the inflammation site. Importance of aceclofenac as a new generational NSAID has inspired the development of topical dosage forms. This mode of administration may help to avoid typical side effects of NSAIDs associated with oral and systemic administration such as gastric irritation, particularly diarrhoea, nausea, abdominal pain and flatulence. The aim of this study was to formulate topical gel containing 1% of aceclofenac in carbopol and PEG base and to evaluate it for analgesic and antiinflammatory activity using carrageenan-induced thermal hyperalgesia and paw oedema in rats. Carrageenan administration into the hind paw produced a significant inflammation associated with hyperalgesia as shown by decreased rat paw withdrawal latency in response to a thermal stimulus (47+/-0.5 degrees C) 4 h after carrageenan injection. Topical application of AF1 significantly attenuated the development of hypersensitivity to thermal stimulus as compared to control (P<0.05) and other formulation treated groups (P<0.05). All the AF semisolid formulations, when applied topically 2 h before carrageenan administration, inhibited paw edema in a timedependent manner with maximum percent edema inhibition of 80.33+/-2.52 achieved with AF1 after 5 h of carrageenan administration However, topical application of AF2 markedly prevented the development of edema as compared to other formulation (AF2 and AF3) treated groups (P<0.05). Among all the semisolid formulations, Carbopol gel base was found to be most suitable dermatological base for aceclofenac.