Xanthurenic acid is an endogenous group II metabotropic glutamate receptor agonist involved in sensory transmission in the thalamus[1]. Xanthurenic acid is synthesized from 3-hydroxykynurenine (3-HK) and may play a physiological role in attention and cognitive processes[2]. Xanthurenic acid can interact with Bcl-2 family proteins, induce mitochondrial apoptosis pathways and impair mitochondrial function[3]. Xanthurenic acid can induce gametogenesis in parasitic Plasmodium[4].
In vitro, Xanthurenic acid (20μM) treatment of vascular smooth muscle cells and retinal pigment epithelial cells for 3h induced mitochondrial damage, resulting in mitochondrial migration, cytochrome c release, and destruction of mitochondria and nucleus[5].
In vivo, Xanthurenic acid (100mg/kg) treated by intraperitoneal injection for 21 days in adult male albino Wistar rats significantly reduced the number of active neurons per channel in the ventral tegmental area (VTA), but did not change the number of firing neurons in the substantia nigra pars compacta (SN)[6].
References:
[1] Copeland C S, Neale S A, Salt T E. Actions of Xanthurenic acid, a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus[J]. Neuropharmacology, 2013, 66: 133-142.
[2] Sathyasaikumar K V, Tararina M, Wu H Q, et al. Xanthurenic acid formation from 3-hydroxykynurenine in the mammalian brain: neurochemical characterization and physiological effects[J]. Neuroscience, 2017, 367: 85-97.
[3] Malina H Z, Hess O M. Xanthurenic acid translocates proapoptotic Bcl-2 family proteins into mitochondria and impairs mitochondrial function[J]. BMC cell biology, 2004, 5: 1-7.
[4] Billker O, Lindo V, Panico M, et al. Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito[J]. Nature, 1998, 392(6673): 289-292.
[5] Malina H Z, Richter C, Mehl M, et al. Pathological apoptosis by xanthurenic acid, a tryptophan metabolite: activation of cell caspases but not cytoskeleton breakdown[J]. BMC physiology, 2001, 1: 1-8.
[6] Taleb O, Maammar M, Klein C, et al. A role for xanthurenic acid in the control of brain dopaminergic activity[J]. International Journal of Molecular Sciences, 2021, 22(13): 6974.
Xanthurenic acid是一种内源性II组代谢型谷氨酸受体激动剂，参与丘脑的感觉传递[1]。Xanthurenic acid由3-羟基犬尿氨酸（3-HK）合成，可能在注意力和认知过程中发挥生理作用[2]。Xanthurenic acid能够与Bcl-2家族蛋白相互作用，诱导线粒体凋亡途径并损害线粒体功能[3]。Xanthurenic acid能够诱导寄生性疟原虫的配子发生[4]。
在体外，Xanthurenic acid（20μM）处理血管平滑肌细胞和视网膜色素上皮细胞3h，诱导了线粒体损伤，导致线粒体迁移、细胞色素c释放以及线粒体和细胞核的破坏[5]。
在体内，Xanthurenic acid（100mg/kg）通过腹腔注射处理成年雄性白化Wistar大鼠21天，显著减少了腹侧被盖区（VTA）中每条通道的活跃神经元数量，但不会改变黑质致密部（SN）中放电神经元的数量[6]。