Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats

Shazia Dawood; Elvis O. Wambiya; Samina Bano

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Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats

机译：双氯芬酸钠抑制大鼠肝脏色氨酸2,3-双加氧酶但增强大鼠脑中吲哚胺2,3-双加氧酶的活性

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Tryptophan2,3-dioxygenase(TDO)existonlyinliverwhileindoleamine2,3-dioxygenase(IDO)existsubiquitouslyinthebody,thesearethemostrate-limitingenzymesofkynureninepathway(KP).Inresponsetoelevatedlevelsofcortisolandpro-inflammatorycytokines,bothenzymesshowincreaseactivityinpatientswithdepressionorAlzheimerdisease(AD).Non-steroidalanti-inflammatorydrugsmayprotectagainstbothdepressionandAD,butobservationalstudieshaveofferedcontradictoryresults.Presentstudyevaluatestheeffectsofanti-inflammatorydiclofenacsodium(DS)onrathepaticTDOandbrainIDOactivities.AdultAlbinoWistarratsweredividedintocontrolandtestgroups,eachtestgroupreceivedDS(2mg/kg)i.p.injectiondailyandwerekilledeitherafter3.5hours(acutetreatment)orafter3,5and7days(chronictreatment)whilecontrolgroupsreceivedanequalvolumeofvehicle.ResultsshowthatTDOenzymeactivitywasinhibitedandlivertryptophanconcentrationswereincreasedafter3to7daystreatmentofDS;howevernoeffectwasseenontheseparametersafter3.5hrs.BrainIDOactivitywasincreasedafterbothacuteandchronicDStreatment.ItisconcludedthatDSinhibitshepaticTDOenzymeactivityfollowingchronictreatment,whileaugmentsbrainIDOactivityfollowingbothacuteandchronicDStreatment,thismayresultinriseincerebralkynurenicacidand/orquinolinicacidconcentrations.ThereforethereisaneedthateffectsofDSonkynureninepathwayshouldbefurtherinvestigatedtoruleouttheprotectiveeffectofDSininflammation-induceddepressionandAlzheimerdisease.

机译：Tryptophan2,3双加氧酶（TDO）existonlyinliverwhileindoleamine2,3双加氧酶（IDO）existsubiquitouslyinthebody，thesearethemostrate-limitingenzymesofkynureninepathway（KP）.Inresponsetoelevatedlevelsofcortisolandpro-inflammatorycytokines，bothenzymesshowincreaseactivityinpatientswithdepressionorAlzheimerdisease（AD）。非甾体inflammatorydrugsmayprotectagainstbothdepressionandAD，butobservationalstudieshaveofferedcontradictoryresults.Presentstudyevaluatestheeffectsofanti-inflammatorydiclofenacsodium（DS）onrathepaticTDOandbrainIDOactivities。 AdultAlbinoWistarratsweredividedintocontrolandtestgroups，eachtestgroupreceivedDS（2毫克/千克）ipinjectiondailyandwerekilledeitherafter3.5hours（acutetreatment）orafter3,5and7days（chronictreatment）whilecontrolgroupsreceivedanequalvolumeofvehicle.ResultsshowthatTDOenzymeactivitywasinhibitedandlivertryptophanconcentrationswereincreasedafter3to7daystreatmentofDS; howevernoeffectwasseenontheseparametersafter3.5hrs.BrainIDOactivitywasincreasedafterbothacuteandchr离子性DS处理。在连续和慢性DS处理后，发现DS抑制了肝的TDO酶活性，而在急性和慢性DS处理之后却增强了脑IDO活性，这可能导致脑中的尿酸和/或喹啉酸浓度升高，从而降低了对DS的保护性，从而降低了对DS的保护性。

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《Journal of Basic and Applied Sciences》 |2016年第21期|共页
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Shazia Dawood; Elvis O. Wambiya; Samina Bano;
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机译：indryl羟胺作为吲哚胺的锅或双抑制剂2,3-二氧基酶-1，indoleamine 2,3-二氧化酶-2和色氨酸二恶英酶
2. A highly efficient modality to block the degradation of tryptophan for cancer immunotherapy: locked nucleic acid-modified antisense oligonucleotides to inhibit human indoleamine 2,3-dioxygenase 1/tryptophan 2,3-dioxygenase expression [J] . Klar Richard, Michel Sven, Schell Monika, Cancer immunology, immunotherapy : . 2020,第1期

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3. Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase [J] . Li Yuanyuan, Zhang Shengnan, Wang Rong, Bioorganic and Medicinal Chemistry Letters . 2020,第11期

机译：新型Tryptanthrin衍生物的合成作为吲哚胺的双抑制剂2,3-二氧合酶1和色氨酸2,3-二氧化根酶
4. Alzheimer’s disease: label-free fluorescence shows increases in indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) activity in affected areas of the brain [C] . Laura A. Sordillo, Lin Zhang, Peter P. Sordillo, Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis . 2019

机译：阿尔茨海默氏病：无标记的荧光显示大脑受影响区域的吲哚胺2，3-双加氧酶（IDO）或色氨酸2，3-双加氧酶（TDO）活性增加
5. Part One. Synthesis of optically active tryptophan derivatives with potential activity as indoleamine 2,3-dioxygenase inhibitors: An approach via asymmetric catalytic hydrogenation. Part Two. Design, synthesis and pharmacology of selective ligands for alpha1-containing GABA(A)/benzodiazepine receptor subtypes: SAR studies of beta-carbolines at positions -3 and -6 and their corresponding bivalent ligands. Part Three. First enantiospecific total synthesis of the important biogenetic intermediates, (+)-polyneuridine and (+)-polyneuridine aldehyde, as well as 16-epi-vellosimine and macusine A. [D] . Yin, Wenyuan. 2007

机译：第一部分。具有吲哚胺2,3-二加氧酶抑制剂潜在活性的旋光色氨酸衍生物的合成：一种通过不对称催化氢化的方法。第二部分。含α1的GABA（A）/苯并二氮杂receptor受体亚型的选择性配体的设计，合成和药理作用：位于-3和-6位的β-咔啉及其相应的二价配体的SAR研究。第三部分。重要生物遗传中间体，（+）-聚神经氨酸和（+）-聚神经氨酸醛，以及16-表-维西辛和Macusine A的首次对映体全合成。
6. MicroRNA-153 Decreases Tryptophan Catabolism and Inhibits Angiogenesis in Bladder Cancer by Targeting Indoleamine 2,3-Dioxygenase 1 [O] . Wentao Zhang, Shiyu Mao, Donghui Shi, 2007

机译：MicroRNA-153通过靶向吲哚胺2,3-双加氧酶1降低色氨酸的代谢并抑制膀胱癌的血管生成。
7. Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase [O] . Maria Winters, James B. DuHadaway, Khoa N. Pham, 2019

机译：indryl羟胺作为吲哚胺的锅或双抑制剂2,3-二氧基酶-1，indoleamine 2,3-二氧化酶-2和色氨酸二恶英酶

Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats

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