bis(1-hydroxy-2-2-6-6-tetramethyl-4-piperidinyl)decandioate and Disease-Models--Animal

bis(1-hydroxy-2-2-6-6-tetramethyl-4-piperidinyl)decandioate has been researched along with Disease-Models--Animal* in 7 studies

Other Studies

7 other study(ies) available for bis(1-hydroxy-2-2-6-6-tetramethyl-4-piperidinyl)decandioate and Disease-Models--Animal

ArticleYear
Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.
    International journal of pharmaceutics, 2016, Oct-15, Volume: 512, Issue:1

    The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), is an innovative non- radical scavenger used with success in numerous disease models such as inflammation, neurological disorders, hepatitis and diabetes. The pharmacological treatments have been performed by the intraperitoneal route of administration, representing to date, the main limit for the drug use. The aim of this study was to develop a delivery system that allows the oral administration of IAC while maintaining its therapeutic efficacy. Solid Lipid Microparticles (SLMs) containing a theoretical 18% (w/w) of IAC have been produced by the spray congealing technology; three formulations have been tested (A, B and C) using different low melting point carriers (stearic acid, Compritol(®) HD5ATO and carnauba wax) alone or in combination. All IAC loaded SLMs exhibited a spherical shape, encapsulation efficiency higher than 94% and particle size suitable for the oral route. Administered per os at different dosages in an inflammation rat model, all SLMs demonstrated their efficacy in reducing oedema and alleviating pain, compared to the gold standards Indomethacin and Paracetamol. These results suggested that the SLMs are an efficacious delivery system for the oral administration of IAC, potentially useful for the treatment of others diseases related to an over production of free radicals.

    Topics: Acetaminophen; Administration, Oral; Animals; Disease Models, Animal; Free Radical Scavengers; Glycerol; Indomethacin; Inflammation; Liposomes; Male; Particle Size; Piperidines; Polyethylene Glycols; Rats; Stearic Acids; Waxes

2016
Anti-inflammatory activity of the non-peptidyl low molecular weight radical scavenger IAC in carrageenan-induced oedema in rats.
    The Journal of pharmacy and pharmacology, 2011, Volume: 63, Issue:3

    In this research we investigated the anti-inflammatory activity of a non-peptidyl low molecular weight radical scavenger (IAC) in an acute and chronic animal model of inflammation.. For this purpose the effect of IAC (10, 25, 50 mg/kg) was tested in rats on the associated behavioral responses to subsequent inflammatory and noxious challenges, such as hind paw oedema induced by intra-plantar injection of carrageenan and granuloma induced by subcutaneous implant of a cotton pellet, using indometacin (2.5 mg/kg) as reference drug. Moreover, the serum level of several cytokines was tested in the animal treated (or not) with IAC (50 mg/kg) both in the absence and presence of carrageenan-induced inflammation.. IAC showed a significant anti-inflammatory activity in both in acute and chronic models of inflammation. In addition IAC down regulated significantly the serum levels of interleukin (IL) 2 and IL6 whereas it increased the serum concentration of IL1α and glutathione.. Although it remains to be elucidated whether or not the antioxidant property of IAC is directly responsible for the modulation of the tested cytokines, these results suggest IAC to be a possible candidate for a novel anti-inflammatory compound.

    Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Down-Regulation; Edema; Free Radical Scavengers; Glutathione; Granuloma, Foreign-Body; Interleukin-1alpha; Interleukin-2; Interleukin-6; Male; Molecular Weight; Piperidines; Rats; Rats, Sprague-Dawley

2011
The radical scavenger IAC (bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decantionate) decreases mortality, enhances cognitive functions in water maze and reduces amyloid plaque burden in hAβPP transgenic mice.
    Journal of Alzheimer's disease : JAD, 2011, Volume: 27, Issue:3

    The purpose of this study was to evaluate the efficacy of the radical scavenger IAC (bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decantionate) in alleviating behavioral deficits and reducing amyloid-β (Aβ) accumulation in an Alzheimer's disease (AD) transgenic Tg2576 mouse model. Daily treatment with IAC (3-30 mg/kg, i.p.) was started at the age of 6 months and continued until the mice were 13 months old. At the age of 9 months and again at 12 months, the mice were tested in open field and water maze tests. At the age of 13 months, the mice were sacrificed and the brains processed for immunohistochemistry. Mortality was significantly reduced in all IAC-treated groups. In addition, IAC treatment improved the water maze hidden platform training performance but had no effect on motor activity in the open field or water maze swim speed in transgenic mice. Lastly, IAC treatment (10 mg/kg) significantly reduced the cortical Aβ plaque burden. In vitro, IAC is able to increase the number of neurites and neurite branches in cultured cortical primary neurons. In conclusion, IAC slowed down the development of the AD-like phenotype in Tg2576 mice and accelerated neurite growth in cultured neurons.

    Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Cell Survival; Cells, Cultured; Cognition; Cricetinae; Disease Models, Animal; Free Radical Scavengers; Male; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Piperidines; Plaque, Amyloid; Rats; Rats, Wistar

2011
Further evidence of the antiulcer activity of IAC, a novel free radical scavenger.
    Pharmacology, 2011, Volume: 88, Issue:3-4

    It has been proposed that free radicals, reactive oxygen species (ROS) and reactive nitrogen species play a critical role in gastric mucosal damage. It is well known that the exposure of gastric mucosa to damaging factors such as stress and nonsteroidal anti-inflammatory drugs produces acute ulcers that are mainly mediated by ROS. The aim of the present study was to investigate the gastroprotective properties of bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC), a novel nonpeptidyl low-molecular-weight radical scavenger, in two different models of gastric ulcer in rats caused by ROS. IAC was orally administered at the doses of 50 and 100 mg/kg before gastric ulceration induced by indomethacin and water immersion and restraint stress. The number and severity of gastric lesions, following macroscopic inspection of the mucosa, were evaluated and expressed as an ulcer score. Oral administration of IAC dosed at 50 and 100 mg/kg was able to significantly prevent gastric ulceration induced by indomethacin and by stress. The gastroprotective effect of IAC on gastric mucosa could be attributed to its intrinsic antioxidant activity, suggesting it as a novel antiulcer agent.

    Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Disease Models, Animal; Free Radical Scavengers; Indomethacin; Male; Piperidines; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stomach Ulcer; Stress, Psychological

2011
The novel radical scavenger IAC is effective in preventing and protecting against post-ischemic brain damage in Mongolian gerbils.
    Journal of the neurological sciences, 2010, Mar-15, Volume: 290, Issue:1-2

    The removal of pathologically generated free radicals produced during ischemia, reperfusion and intracranical hemorrhage seems to be a viable approach to neuroprotection. However, at present, no neuroprotective agent has proven effective in focal ischemic stroke phase III trials, despite the encouraging data in animal models. This study aimed to explore the effect of the brain penetrant low molecular weight radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in neurological damage subsequent to ischemia-reperfusion injury in Mongolian gerbils. We examined the intraperitoneal effects of IAC on temporary bilateral common carotid artery occlusion (BCCO) by means of morphological and histological analysis of the hippocampus. Significant dose-dependent protective effects of IAC (1 to 10mg/kg b.w.) against neuropathological and morphological brain changes were seen when administered i.p. 1h before temporary BCCO in Mongolian gerbils. When administered up to 6h after BCCO, IAC actually reverses the neurodegenerative processes (e.g. hippocampal cell viability) induced by ischemia in a dose-dependent fashion. Data show that IAC is highly effective in protecting and preventing oxidative brain damage associated with cerebral flow disturbances. It is also effective even in late treatment of the insult, emphasizing its potential role for the management of ischemic stroke patients.

    Topics: Animals; Brain Damage, Chronic; Brain Infarction; Brain Ischemia; Carotid Stenosis; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Gerbillinae; Hippocampus; Infusions, Parenteral; Male; Nerve Degeneration; Neuroprotective Agents; Oxidative Stress; Piperidines; Treatment Outcome

2010
Anti-ulcer activity of IAC, a novel free-radical scavenger, in rats.
    The Journal of pharmacy and pharmacology, 2009, Volume: 61, Issue:3

    We investigated the ability of a novel low-molecular-weight free-radical scavenger, bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), to protect the gastric mucosa from indometacin-induced ulceration.. The pharmacological effects of IAC, administered orally or by intraperitoneal injection, on the gastric mucosa were assessed in a rat model of gastric ulceration induced by indometacin. The effect of IAC on the level of prostaglandin PGE2 in the gastric mucosa was also investigated.. IAC, which has no ulcerative activity per se, had a preventive and protective activity against indometacin-induced gastric ulceration. This effect could be only partially attributed to a modulatory effect of IAC on PGE2 levels; it is more likely to be due to the antioxidant activity of the compound.. Taking into account the properties of IAC and the mechanisms underlying gastric inflammation elicited by non-steroidal anti-inflammatory drugs, IAC may represent a novel anti-ulcer agent.

    Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Dinoprostone; Disease Models, Animal; Esters; Free Radical Scavengers; Gastric Mucosa; Indomethacin; Injections, Intraperitoneal; Male; Piperidines; Rats; Rats, Sprague-Dawley; Stomach Ulcer

2009
Neuroprotective properties of the non-peptidyl radical scavenger IAC in rats following transient focal cerebral ischemia.
    Brain research, 2008, May-01, Volume: 1207

    Experimental evidence suggests that reactive free radicals are generated during brain ischemia. We investigated the effect of a novel brain penetrant, low molecular weight, non-peptidyl carbon, oxygen- and nitrogen-centered radical scavenger, IAC, on infarct volume and sensory-motor performance in a rat transient middle cerebral artery occlusion model (tMCAO). Rats received 90 min tMCAO and treated with i.p. or i.v. injections of vehicle or IAC following tMCAO. Sensory-motor performance was evaluated by neuroscore tests (NS). Cerebral infarct volume was evaluated at 72 h after tMCAO. Rats treated with IAC i.p. (1 or 6 h after the onset of tMCAO) or i.v. (1 h after the onset of tMCAO) showed significant improvement in NS during the 3 or 21 day follow-up period when compared to vehicle treated rats. Cerebral infarct volumes were significantly decreased compared to vehicle in rats receiving IAC i.p. 1 h or 6 h after occlusion, approximately 30.5% decrease compared to vehicle, or i.v. 1 h after the onset of tMCAO, 48.6% decrease compared to vehicle. These results demonstrate that IAC has neuroprotective properties with a wide therapeutic window following tMCAO in rats. IAC could therefore be a candidate for the treatment of stroke.

    Topics: Analysis of Variance; Animals; Behavior, Animal; Cerebral Infarction; Disease Models, Animal; Dose-Response Relationship, Drug; Esters; Ischemic Attack, Transient; Male; Neuroprotective Agents; Piperidines; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Time Factors

2008