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Acetyl Cysteine (acetyl + cysteine)
Selected AbstractsEffect of N -Acetyl Cysteine against Aluminium-induced Cognitive Dysfunction and Oxidative Damage in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Atish Prakash Chronic aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. The role of oxidative stress has been well-suggested in these cognitive problems. Therefore, the present study was designed to explore the possible role of N -acetyl cysteine against aluminium mediating cognitive dysfunction and oxidative stress in rats. Aluminium chloride (100 mg/kg, p.o.) was given to rats daily for 6 weeks. N -acetyl cysteine (per se; 50 and 100 mg/kg, i.p.) pre-treatment was given 30 min. before aluminium daily for 6 weeks. On the third (21st day) and sixth week (42nd day) of the study, various behavioural tests (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done to evaluate cognitive tasks. The rats were killed on the 43rd day following the last behavioural test, and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity. Chronic administration of N -acetyl cysteine significantly improved memory retention in tasks, attenuated oxidative damage and acetylcholinesterase activity in aluminium-treated rats. The study suggests a neuroprotective effect of N -acetyl cysteine against aluminium-induced cognitive dysfunction and oxidative damage. [source] Characterization of Cd-induced molecular events prior to cellular damage in primary rat hepatocytes in culture: Activation of the stress activated signal protein JNK and transcription factor AP-1JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2004Chin-ju J. Hsiao Abstract The effect of Cadmium (Cd) on the expression of c-Jun N -terminal kinase (JNK), c-jun, and activator protein-1 (AP-1) has been investigated. We previously reported that Cd causes cell damage as indicated by increases in the cytotoxic parameters, lactate dehydrogenase and lipid peroxidation, and this damage was mediated by decreases in cellular concentration of glutathione. In the present study, we investigate the molecular events involved prior to the Cd-induced cellular toxicity and damage in primary rat hepatocytes. We propose that Cd, through the generation of reactive oxygen species (ROS) and prior to significant cellular damage, activates the stress activated signal protein JNK, regulates c-jun expression, and promotes the binding of a redox sensitive transcription factor AP-1. We show JNK activity and c-jun mRNA level significantly increased at 1 h and AP-1 DNA binding activity significantly enhanced at 3 h in the presence of 4 ,M cadmium chloride. Blocking the Cd induction of JNK activity, c-jun mRNA level, and AP-1 binding activity using the antioxidants N -acetyl cysteine (10 mM) or carnosol (0.5 ,g/mL) suggests a role for ROS. Blocking JNK activity and c-jun mRNA by SP600125 (20 ,M), a JNK inhibitor, supports the role of JNK in transmission of signals induced by Cd. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:133,142, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20018 [source] Decreased oxidative stress and greater bone anabolism in the aged, when compared to the young, murine skeleton with parathyroid hormone administrationAGING CELL, Issue 5 2010Robert L. Jilka Summary Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. Parathyroid hormone produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26- when compared to 6 -month-old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae, and the toughness of both vertebrae and femora in old, but not young, mice. Parathyroid hormone also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species, p66Shc phosphorylation, and expression of the lipoxygenase Alox15, and it increased glutathione and stimulated Wnt signaling in bone of old mice. Parathyroid hormone also antagonized the effects of oxidative stress on p66Shc phosphorylation, Forkhead Box O transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N -acetyl cysteine or pegylated catalase reduced osteoblast progenitors and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation, it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling. [source] Modulation of peroxisome proliferator-activated receptor-, activity by N -acetyl cysteine attenuates inhibition of oligodendrocyte development in lipopolysaccharide stimulated mixed glial culturesJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Manjeet K. Paintlia Abstract Glial cells secrete proinflammatory mediators in the brain in response to exogenous stimuli such as infection and injury. Previously, we documented that systemic maternal lipopolysaccharide (LPS)-exposure at embryonic gestation day 18 causes oligodendrocyte (OL)-injury/hypomyelination in the developing brain which can be attenuated by N -acetyl cysteine (NAC; precursor of glutathione). The present study delineates the underlying mechanism of NAC-mediated attenuation of inhibition of OL development in LPS-stimulated mixed glial cultures. Factors released by LPS-stimulated mixed glial cultures inhibited OL development as shown by decrease in both proliferation 3bromo-deoxyuridine+/chondroitin sulfate proteoglycan,NG2+, hereafter BrdU+/NG+ and differentiation (O4+ and myelin basic protein+) of OL-progenitors. Correspondingly, an impairment of peroxisomal proliferation was shown by a decrease in the level of peroxisomal proteins in the developing OLs following exposure to LPS-conditioned media (LCM). Both NAC and WY14643, a peroxisome proliferator-activated receptor (PPAR)-, agonist attenuated these LCM-induced effects in OL-progenitors. Similar to WY14643, NAC attenuated LCM-induced inhibition of PPAR-, activity in developing OLs. Studies conducted with cytokines and diamide (a thiol-depleting agent) confirmed that cytokines are active agents in LCM which may be responsible for inhibition of OL development via peroxisomal dysfunction and induction of oxidative stress. These findings were further corroborated by similar treatment of developing OLs generated from PPAR-,(,/,) and wild-type mice or B12 oligodendroglial cells co-transfected with PPAR-, small interfering RNAs/pTK-PPREx3-Luc plasmids. Collectively, these data provide evidence that the modulation of PPAR-, activity, thus peroxisomal function by NAC attenuates LPS-induced glial factors-mediated inhibition of OL development suggesting new therapeutic interventions to prevent the devastating effects of maternal infections. [source] Effect of N -Acetyl Cysteine against Aluminium-induced Cognitive Dysfunction and Oxidative Damage in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Atish Prakash Chronic aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. The role of oxidative stress has been well-suggested in these cognitive problems. Therefore, the present study was designed to explore the possible role of N -acetyl cysteine against aluminium mediating cognitive dysfunction and oxidative stress in rats. Aluminium chloride (100 mg/kg, p.o.) was given to rats daily for 6 weeks. N -acetyl cysteine (per se; 50 and 100 mg/kg, i.p.) pre-treatment was given 30 min. before aluminium daily for 6 weeks. On the third (21st day) and sixth week (42nd day) of the study, various behavioural tests (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done to evaluate cognitive tasks. The rats were killed on the 43rd day following the last behavioural test, and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity. Chronic administration of N -acetyl cysteine significantly improved memory retention in tasks, attenuated oxidative damage and acetylcholinesterase activity in aluminium-treated rats. The study suggests a neuroprotective effect of N -acetyl cysteine against aluminium-induced cognitive dysfunction and oxidative damage. [source] | ||||||||||