Effect of Cysteine Ethylester Hydrochloride (Cystanin®) on Host Defense Mechanisms (V): Potentiation of Nitroblue Tetrazolium Reduction and Chemiluminescence in Macrophages or Leukocytes of Mice or Rats

Hisadome, Masao; Fukuda, Tetsuko; Terasawa, Michio

doi:10.1254/jjp.53.57

Cited by 4 publications

(2 citation statements)

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“…Finally, our finding that NLX elicited a substantial increase in apneic events is new to our morphine-dependence model, but also consistent with findings in rats ( Baraban et al, 1993 ; Baldo, 2022 ) and humans ( Schwarzer et al, 2015 ; Zamani et al, 2020 ; Wilson et al, 2023 ). The inability of L-cysteine to modify the NLX-precipitated withdrawal phenomena certainly suggests that the efficacy of L-CYSee involves the entry of this cell-penetrant L-thiol ester ( Goto et al, 1983 ; Hisadome et al, 1986a ; Hisadome et al, 1986b ; Hisadome et al, 1988 ; Servin et al, 1988 ; Hisadome et al, 1990 ; Schöneich et al, 1992 ; Hobbs et al, 1993 ; Fukui et al, 1994 ; Ding and Demple, 1998 ; Galanakis et al, 2004 ; Mosier-Boss and Lieberman, 2005 ; Perissinotti et al, 2005 ; Defonsi Lestard et al, 2013 ; Mendoza et al, 2013 ; Arias et al, 2019 ; Lewis et al, 2022 ) into neurons involved in the acquisition of physical dependence/addiction on morphine ( Laschka et al, 1976a ; Laschka et al, 1976b ; Laschka and Herz, 1977 ; Koob, 1987 ; Saiepour et al, 2001 ; Glass, 2010 ; Gardner, 2011 ; Glass, 2011 ). Moreover, the inability of L-SERee to prevent the acquisition of physical dependence on morphine indicates that the sulfur atom is vital to the ability of L-CYSee to prevent the intracellular processes within the brain by which morphine induces physical dependence ( Deslandes et al, 2002 ; Gardner, 2011 ; Koob and Volkow, 2016 ; Volkow et al, 2019 ; Koob, 2020 ; Sakloth et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Some of the temporal steps described by Trivedi et al (2014) (see Figure 5 of Trivedi et al, 2014 ) and others ( Lin et al, 2001 ; Ikemoto et al, 2002 ; Mao et al, 2002 ; Xu et al, 2003 ; Xu et al, 2006 ; Christie, 2008 ; Yang et al, 2008 ; Wang et al, 2009 ; Daijo et al, 2011 ; Gutowicz et al, 2011 ; Liu et al, 2011 ; Maze and Nestler, 2011 ; Lim et al, 2012 ; Sun et al, 2012 ; Browne et al, 2020 ) are as follows: 1) morphine blockade of L-cysteine uptake into neurons by G protein-dependent inhibition of EAA3 activity, 2) resulting decreases in intracellular levels of L-cysteine, L-glutathione, and the methylation index, namely, S-adenosyl-methionine/S-adenosyl-homocysteine (SAM/SAH ratio), 3) decreases in the methylation status of global CpG (regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5′ → 3′ direction) and in CpG methylation of long interspersed nuclear element-1 (LINE-1) retrotransposon regulatory regions, and 4) activation of transcription of previously silenced LINE-1 genes. Thus, we hypothesized that co-administration of cell-permeant versions of L-cysteine, such as L-cysteine ethyl ester (L-CYSee) ( Goto et al, 1983 ; Hisadome et al, 1986a ; Hisadome et al, 1986b ; Hisadome et al, 1988 ; Servin et al, 1988 ; Hisadome et al, 1990 ; Schöneich et al, 1992 ; Hobbs et al, 1993 ; Fukui et al, 1994 ; Ding and Demple, 1998 ; Galanakis et al, 2004 ; Mosier-Boss and Lieberman, 2005 ; Perissinotti et al, 2005 ; Defonsi Lestard et al, 2013 ; Mendoza et al, 2013 ; Arias et al, 2019 ), may prevent the acquisition of physical dependence on morphine and reverse established dependence on the opioid. Previously, we reported that L-CYSee ( Lewis et al, 2022 ), L-cysteine methyl ester ( Getsy et al, 2022a ), and other thiolesters and related compounds ( Baby et al, 2021 ; Baby et al, 2021 ; Gaston et al, 2021 ; Jenkins et al, 2021 ; Getsy et al, 2022b ; Getsy et al, 2022c ; Getsy et al, 2022d ;…”

Section: Introductionmentioning

confidence: 99%

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L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats

Bates,

Getsy,

Coffee

et al. 2023

Front. Pharmacol.

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The molecular mechanisms underlying the acquisition of addiction/dependence on morphine may result from the ability of the opioid to diminish the transport of L-cysteine into neurons via inhibition of excitatory amino acid transporter 3 (EAA3). The objective of this study was to determine whether the co-administration of the cell-penetrant L-thiol ester, L-cysteine ethyl ester (L-CYSee), would reduce physical dependence on morphine in male Sprague Dawley rats. Injection of the opioid-receptor antagonist, naloxone HCl (NLX; 1.5 mg/kg, IP), elicited pronounced withdrawal phenomena in rats which received a subcutaneous depot of morphine (150 mg/kg) for 36 h and were receiving a continuous infusion of saline (20 μL/h, IV) via osmotic minipumps for the same 36 h period. The withdrawal phenomena included wet-dog shakes, jumping, rearing, fore-paw licking, 360° circling, writhing, apneas, cardiovascular (pressor and tachycardia) responses, hypothermia, and body weight loss. NLX elicited substantially reduced withdrawal syndrome in rats that received an infusion of L-CYSee (20.8 μmol/kg/h, IV) for 36 h. NLX precipitated a marked withdrawal syndrome in rats that had received subcutaneous depots of morphine (150 mg/kg) for 48 h) and a co-infusion of vehicle. However, the NLX-precipitated withdrawal signs were markedly reduced in morphine (150 mg/kg for 48 h)-treated rats that began receiving an infusion of L-CYSee (20.8 μmol/kg/h, IV) at 36 h. In similar studies to those described previously, neither L-cysteine nor L-serine ethyl ester (both at 20.8 μmol/kg/h, IV) mimicked the effects of L-CYSee. This study demonstrates that 1) L-CYSee attenuates the development of physical dependence on morphine in male rats and 2) prior administration of L-CYSee reverses morphine dependence, most likely by intracellular actions within the brain. The lack of the effect of L-serine ethyl ester (oxygen atom instead of sulfur atom) strongly implicates thiol biochemistry in the efficacy of L-CYSee. Accordingly, L-CYSee and analogs may be a novel class of therapeutics that ameliorate the development of physical dependence on opioids in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats

Bates,

Getsy,

Coffee

et al. 2023

Front. Pharmacol.

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Effect of Diethylcarbamazine Citrate and Setaria equina Excretory–Secretory Material on Rat Hepatocellular Carcinoma

Abdel‐Latif

Sakran

El-Shahawi

et al. 2014

Arch. Immunol. Ther. Exp.

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Diethylcarbamazine citrate (DEC) has been known for its efficacy to eradicate bancroftian filariasis in Egypt and other countries in the world. One of the known effects was to decrease the level of circulating filarial antigen in the patient's serum. The target of this study was to examine the effect of DEC, excretory-secretory (ES) material from the filarial parasite Setaria equina or a combination of both on the status of oxidative stress and pathogenesis of rat hepatocellular carcinoma (HCC) induced by diethylnitrosamine and 2-acetylaminofluorene. This could be tested in vitro using nitroblue tetrazolium reduction test for measuring the level of superoxide anion (O₂(•-)) released from rat peritoneal macrophages. For in vivo test, a single dose before induction of carcinogenesis or continually repeated doses with DEC, ES or DEC + ES was used. Exposure of macrophages to ES could lead to a significant decrease (p < 0.01) in O₂(•-) release, while DEC (200 μM) could modulate such effect with significant increase (p < 0.05). Pathogenesis of liver cancer and treatment were evaluated using histological investigation, level of antioxidant and liver function enzymes. Repeated ES doses could increase the activity of antioxidant enzymes, especially the catalase enzyme and show a protective effect on liver architecture. DEC could modulate the later effects when combined with ES. No significant effect on the liver function enzymes after treatment was observed. Nuclear factor κB was found to be localized only in the cytoplasm after single and repeated treatments with ES. This study could indicate the effect of S. equina ES as antioxidant against rat HCC, while DEC could modulate such effect when combined with it.

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2001

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Concern is growing regarding the impact of chemicals suspected of altering the function of the immune system in humans and wildlife. There are numerous examples of links between pollution and increased susceptibility to disease in wildlife species, including immunosuppression in harbour seals feeding on fish from contaminated sites, altered immune function in riverine fish and decreased host resistance in birds exposed to pollutants. Laboratory tests have identified potential immunological hazards posed by a range of anthropogenic chemicals in mammals and higher vertebrates. However, few reports have considered the ecological relevance of pollution-induced immunosuppression in invertebrate phyla, which constitute around 95% of all animal species and occupy key structural and functional roles in ecosystems. In this paper effects of chemicals on immune function in invertebrates are briefly reviewed and biomarkers of immunotoxicity are identified. Examples of new approaches for the measurement of immunological inflammatory reactions and stress in molluscan haemocytes are detailed. The relevance of defining the immune system as a target organ of toxicity in invertebrates is discussed and an integrated approach for the use of immunological biomarkers in environment management is proposed, combining measures of immune function and organismal viability at the biochemical, cellular and population level.

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Effect of Cysteine Ethylester Hydrochloride (Cystanin®) on Host Defense Mechanisms (V): Potentiation of Nitroblue Tetrazolium Reduction and Chemiluminescence in Macrophages or Leukocytes of Mice or Rats

Cited by 4 publications

References 24 publications

L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats

L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats

Effect of Diethylcarbamazine Citrate and Setaria equina Excretory–Secretory Material on Rat Hepatocellular Carcinoma

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