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Biochemical Markers in Ophthalmology
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Abdus Samad Ansari, Pirro G. Hysi
Neurodegeneration, elevated IOP, and oxidative stress are among the factors leading to disease development and progression. Metabolomic studies have looked to evaluate how we can better identify metabolic changes in these patients. Markers for oxidative stress have been found in both serum and aqueous samples. These include 2-mercaptoethanesulfonic acid, d-erythronolactone, dehydroascorbic acid, galactose, mannose, pelargonic acid, ribitol, N-acetyl-l-leucine, RAC-glycerol 1-myristate, arginine, 1-oleoyl-RAC-glycerol, and cystathionine [121, 122]. One systematic review identified malonyldialdehyde as one of the best biomarkers for oxidative stress in serum for patients with glaucoma [123]. Other studies have indicated that spermine and spermidine may play a metabolic role in individuals with POAG [122], potentially affecting mitochondrial membrane potential, thus influencing a degree of neuroprotection on the optic nerve. More recently a metabolome-wide association study employing machine learning and Mendelian randomization found that levels of O-methylascorbate, a circulating product of vitamin C metabolism, significantly lowered IOP in subjects from the general population [124].
Physiology and Growth
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Spermine, known as one of a number of compounds stabilizing spheroplasts to lysis in distilled water, demonstrated its stabilizing effect on the f2-infected cells by complete prevention or interruption of the phage release, although phage reproduction was markedly inhibited (Groman 1966; Groman and Suzuki 1966). The degree of inhibition was constant over the range of concentrations tested but was roughly related to the time of addition: significant inhibition was observed even when spermine was added as late as 30 min after infection, which was just before lysis began in the control (Groman and Suzuki 1966).
Biochemical and Pharmacological Rationales in Radiotracer Design
Published in Lelio G. Colombetti, Principles of Radiopharmacology, 2019
Raymond E. Counsell, Nancy Korn
The polyamines, spermidine and spermine, and their precursor putrescine are ubiquitous in nature. These substances are synthesized from L-ornithine in higher animals according to the pathway shown in Figure 20.
Modulation of mitochondrial permeability transition pore opening by Myricetin and prediction of its-drug-like potential using in silico approach
Published in Drug and Chemical Toxicology, 2023
Akinwunmi O. Adeoye, John A. Falode, Olabimpe C. Oladipupo, Tajudeen O. Obafemi, Babatunde J. Oso, Ige F. Olaoye
The assessment of calcium (the reference triggering agent), other toxicants (aluminum chloride, mercury sulfate lead acetate, and glucose), and spermine are presented in Figure 1. There was no significant change (decrease) observed in the absorbance of mitochondria recorded at 540nm in the absence of calcium which indicated the intactness of the isolated mitochondria. However, a significant reduction in the absorbance was observed in the presence of triggering agents (exogenous calcium) and other toxicants which indicated a large amplitude mitochondrial swelling. The opening of the MPT pore by calcium was significantly higher than other toxicants used in this study. The induction fold of calcium, aluminum chloride, mercury sulfate, lead acetate, and glucose are 20.61, 13.52, 12.35, 10.97, and 8.52 respectively. Spermine significantly inhibited the opening of the pore by 87.48%.
Role of the mitochondrial calcium uniporter in Mg2+-free-induced epileptic hippocampal neuronal apoptosis
Published in International Journal of Neuroscience, 2020
Yingjiao Li, Cui Wang, Yajun Lian, Haifeng Zhang, Xianghe Meng, Mengyan Yu, Yujuan Li, Nanchang Xie
Mitochondrial Ca2+ homeostasis is critical for cell survival. Mitochondrial Ca2+ overload can induce cell apoptosis by increasing ROS production, promoting opening of the mPTP, and inducing the release of cytochrome c [18]. In this study, we found that inhibition of the MCU can protect neurons from apoptosis and attenuate neuronal damage induced by AE. We also found that the MCU inhibitor Ru360 reversed the seizure-induced mitochondrial Ca2+ concentration increase and production of mitochondrial ROS, while the mMP level decreased. However, the MCU activator spermine exerted the opposing effects. In addition, Ru360 and spermine did not have a detectable impact on the concentration of mitochondrial Ca2+ [19, 20]. We hypothesized that Ru360 and spermine exerted effects on the basis of the MCU activation induced by seizures. These results support extant findings of previous studies indicating that spermine could exacerbate oxidative stress induced by ischemia–reperfusion [21]. However, a recent study reported that Pb2+-induced ROS production was potentiated by Ru360 or MCU knockdown and reversed by spermine or MCU overexpression [5]. Although the effect of MCU on oxidative stress requires further study, the studies described herein suggest that MCU plays a crucial role in the oxidative stress response.
Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?
Published in Expert Opinion on Therapeutic Targets, 2020
Jo Nijs, Sevilay Tumkaya Yilmaz, Ömer Elma, Joe Tatta, Patrick Mullie, Luc Vanderweeën, Peter Clarys, Tom Deliens, Iris Coppieters, Nathalie Weltens, Lukas Van Oudenhove, Eva Huysmans, Anneleen Malfliet
Polyamines represent another potential therapeutic target in the area of nutritional interventions for the prevention of post-surgical pain. Polyamines are cationic organic molecules present in all living organisms, with spermidine, spermine, and their precursor putrescine as the main polyamines in mammalian cells [71]. Human gut bacteria synthesize and transport polyamines [71], and polyamine levels increase with inflammation [72]. Polyamines are thought to be involved in the regulation of numerous metabolic and electrophysiological processes in the nervous system, including scavenging of reactive oxygen species, and alteration of polyamine metabolism has been identified in neurodegenerative disease and several types of cancer, resulting in the increased interest of exogenous administration of natural polyamines as innovative treatment [71]. Animal studies support the idea that a polyamine-deficient dietary pattern has analgesic effects on inflammatory pain [73] and reduces pain hypersensitivity [74]. Excitation of N-methyl-D-aspartate (NMDA) receptors is an essential component of the central nervous system sensitization, with polyamines holding the capacity to modulate them [72]. Polyamine-deficient dietary pattern is thought to inhibit tyrosine phosphorylation of the NMDA receptors [72], thereby potentially decreasing the sensitivity of the (central) nervous system.