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Powerful Inhibitor (powerful + inhibitor)
Selected AbstractsCatechin as an antioxidant in liver mitochondrial toxicity: Inhibition of tamoxifen-Induced protein oxidation and lipid peroxidation,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2007Heena Tabassum Abstract Tamoxifen (TAM) is a nonsteroidal triphenylethylene antiestrogenic drug widely used in the treatment and prevention of breast cancer. TAM brings about a collapse of the mitochondrial membrane potential. It acts both as an uncoupling agent and as a powerful inhibitor of mitochondrial electron transport chain. The effect of catechin pretreatment on the mitochondrial toxicity of TAM was studied in liver mitochondria of Swiss albino mice. TAM treatment caused a significant increase in the mitochondrial lipid peroxidation (LPO) and the protein carbonyls (PCs). It also caused a significant increase in superoxide radical production. Pretreatment of mice with catechin (40 mg/kg) showed significant protection as demonstrated by marked attenuation of increased oxidative stress parameters such LPO, PCs, and superoxide production. It also restored the decreased nonenzymatic and enzymatic antioxidants of mitochondria. The inhibitory effect of catechin on TAM-induced oxidative damage suggests that it may have potential benefits in prevention of human diseases where reactive oxygen species have some role as causative agents. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:110,117, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20167 [source] Prenatal testosterone treatment potentiates the aggression-inhibiting effect of the neurosteroid dehydroepiandrosterone in female miceAGGRESSIVE BEHAVIOR, Issue 2 2001Fabrice Perché Abstract The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of aggression in murine models when given for 15 days and potentially may be useful in the management of inappropriate human aggression. Although the biosynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentiation on the subsequent response to DHEA. Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the effect of DHEA (80 ,g/d) on aggression in female offspring where dams were treated with 1, 10, or 100 ,g of testosterone (T) on days 15 to 18 of gestation (Experiment I) or that developed in different uterine positions (Experiment II). The results showed that DHEA decreased attack behavior in general and that the 100-,g prenatal T treatments enhanced the antiaggressive effect of this neurosteroid. Neither the lower doses of exogenously administered T nor the uterine position led to an enhanced response to DHEA. In addition, whether DHEA produced changes in social and nonsocial activities was examined. In the 100-,g T females, DHEA increased the duration of the former and decreased the frequency and duration of the latter, indicating that it was not a general decrement in behavioral expression that mediated the enhanced response to the antiaggressive effect of DHEA. In the second experiment, DHEA treatment led to increased frequencies of social nonaggressive and nonsocial activities. However, the uterine positions × treatment interactions were not significant, demonstrating that contiguity to male fetuses did not differentially affect the response to DHEA. Aggr. Behav. 27:130,138, 2001. © 2001 Wiley-Liss, Inc. [source] Osteoprotegerin in the Inner Ear May Inhibit Bone Remodeling in the Otic Capsule,THE LARYNGOSCOPE, Issue 1 2005Andreas F. Zehnder MD Abstract Objectives: To elucidate factors that may be responsible for the inhibition of remodeling of bone within the otic capsule. Methods: Expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK), and RANK ligand (RANKL) were assayed in samples of bone obtained from the otic capsule, calvarium, and femur, and from the soft tissue within the cochlea using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in mice. Immunostaining was used for histologic localization of the gene products. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the amount of OPG within perilymph, serum, and cerebrospinal fluid. The micro-anatomy of the interface between the otic capsule and the fluid spaces of the cochlea was investigated by brightfield and phase-contrast microscopy and by three-dimensional reconstruction in the mouse and human. Results: OPG, a powerful inhibitor of bone remodeling, was expressed at extremely high levels within the soft tissue of the cochlea and was present in the perilymph at very high concentrations. The OPG produced within the inner ear may diffuse into the surrounding otic capsule, where it may be responsible for inhibition of bone turnover. Our anatomic studies revealed an extensive system of interconnected canaliculi within the otic capsule that had direct openings into the fluid spaces of the inner ear, thus providing a possible anatomic route for the diffusion of OPG from the inner ear into the surrounding bone. Conclusion: OPG, a potent inhibitor of osteoclast formation and function, is expressed at high levels within the inner ear and is secreted into the perilymph and the surrounding bone and may serve to inhibit active bone remodeling within the otic capsule, especially immediately adjacent to the cochlea. By this means, the cochlear soft tissue may control the nature of the surrounding petrous bone. [source] Inhibition of human platelet aggregation by a novel S-nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti-thrombotic therapyBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000Ian L Megson S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet effects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the effects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggregation. The effects of GSNO and RIG200 in collagen (2.5 ,g ml,1)-induced platelet aggregation in PRP and whole blood were investigated in vitro. Both compounds were found to be powerful inhibitors of aggregation in PRP, and RIG200 was significantly more potent (IC50=2.0 ,M for GSNO and 0.8 ,M for RIG200; P=0.04). Neither compound inhibited aggregation in whole blood, even at concentrations of 100 ,M. Red blood cell concentrations as low as 1% of the haematocrit, and cell-free haemoglobin (2.5 ,M), significantly reduced their inhibitory effects on platelets. Experiments involving measurement of cyclic GMP levels, electrochemical detection of NO and electron paramagnetic resonance of haemoglobin in red blood cells, indicated that scavenging of NO generated from S-nitrosothiols by haemoglobin was responsible for the lack of effect of S-nitrosothiols on platelets in whole blood. These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents. British Journal of Pharmacology (2000) 131, 1391,1398; doi:10.1038/sj.bjp.0703731 [source] | ||||||||||