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Medicinal Potential of Fenugreek in Neuropathy and Neuroinflammation Associated Disorders
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Aman Upaganlawar, Chandrashekhar Upasani, Mayur B. Kale
Apart from inflammation, the oxidative damage-induced chronic stress in the brain includes increased production of 4-hydroxynonenal, results from LPO, which disturbs the integrity of the membrane and results in inhibition of Ca2+ATPase and MAO, which acts as a contributing factor in the progression of PN (Baquer et al. 2009).
The Effects of Resveratrol on the Brain Mitochondria
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Recently, Folbergrová et al. (2018) have found that RES (25 mg/kg, i.p., in both acute and chronic protocols, as detailed in Table 2) protected mitochondria in the cerebral cortex of young rats subjected to epileptogenesis induced by Li-pilocarpine [101]. RES restored the activity of complex I and reduced the levels of nitrated proteins in the organelles. Besides, RES decreased the amounts of 4-hydroxynonenal in cortical mitochondria obtained from Li-pilocarpine-treated rats. The mechanism of action of RES in protecting mitochondria was not addressed by the authors in that work. Therefore, it is necessary to find how RES rescued mitochondrial function due to the pharmacological importance of the data obtained by the authors. Several patients present a drug resistance regarding the treatment of epilepsy [102]. Thus, it is necessary to obtain new drugs that would be able to attenuate the impact of epilepsy mainly in young individuals. This would increase the life quality of the subjects suffering from epilepsy in a very important moment of their life, in which learning capability, as well as other cognitive functions, needs to be preserved.
Micronutrients in Prevention and Improvement of the Standard Therapy in Arthritis
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
A review has shown that increased oxidative stress play a central role in pathophysiology of OA.27 Among reactive aldehydes, 4-hydroxynonenal (HNE) is considered the most reactive species, and like ROS, HNE can induce various biological effects including apoptosis. Antioxidants such as N-acetylcysteine (NAC), and overexpression of glutathione-s-transferase A4-4 reduced HNE production and inhibited apoptosis in several cells. The levels of HNE were higher in synovial fluid of patients with OA than those found in healthy subjects.28 It has been demonstrated that HNE can induce transcriptional and posttranscriptional modifications of type II collagen and matrix metalloproteinase-13 (MMP-13), resulting in extracellular matrix in cartilage from patients with OA.28
Acutely increased aquaporin-4 exhibits more potent protective effects in the cortex against single and repeated isoflurane-induced neurotoxicity in the developing rat brain
Published in Toxicology Mechanisms and Methods, 2023
Habip Yılmaz, Aslıhan Şengelen, Serdar Demirgan, Hüsniye Esra Paşaoğlu, Melike Çağatay, İbrahim Emre Erman, Mehmet Bay, Hasan Cem Güneyli, Evren Önay-Uçar
To the best of our knowledge, we investigated and compared, for the first time, acute apoptotic, inflammatory, and oxidative responses of the developing rat brain against single and repeated anesthetic exposure to isoflurane (Iso) and how the aquaporin 4 (AQP4) expression levels changed in the hippocampus, cerebellum, and cortex during this process. The principal findings of our research were as follows: (1) while both single and repeated anesthesia caused damage at an early age, the effects of multiple Iso exposure were more severe. (2) Apoptotic responses due to anesthesia were most common in the hippocampus. (3) Oxidative damage was determined primarily on the cerebellum. (4) 4-hydroxynonenal (4HNE, an oxidative stress marker) and tumor necrosis factor (TNF)-α (a proinflammatory cytokine) contributed synergistically to Iso-induced neurotoxicity. (5) AQP4 levels were highest in the cortex after anesthesia applications compared to the hippocampus and cerebellum. (6) There was an inverse correlation between increased AQP4 levels and apoptosis, inflammation, and ROS markers; the correlation with 4HNE was strong. These results suggest that AQP4 had a more substantial protective profile in the developing brain against oxidative stress and exhibited a more potent neuroprotective effect in the cortex, especially the frontal cortex.
A mechanistic overview of spinal cord injury, oxidative DNA damage repair and neuroprotective therapies
Published in International Journal of Neuroscience, 2023
Jaspreet Kaur, Aditya Mojumdar
Excess mitochondrial Ca2+ activates Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) which enables superoxide generation by electron transport chain (ETC). NOX and ETC mainly produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) leading to the activation of poly-ADP-ribose polymerase (PARP). Activity of PARP results in cell death due to ATP depletion and compromised glycolysis, and by apoptosis inducing factor, AIF [59]. The consequent ROS and RNS mainly target lipids, proteins and nucleic acids, resulting in the oxidation of these molecules [21, 66]. ROS react with chains of unsaturated fatty acids, producing lipid peroxyl radicals, which start a chain reaction by reacting with the neighbouring unsaturated fatty acid in the membrane. The highly toxic final products of the lipid peroxidation reaction are 4-hydroxynonenal and 2-propenal contributing to cell death [21, 37, 67–69]. Amino acids/proteins are the targets of RNS, oxidation of amino acids are deleterious resulting in protein damage, for example, nitration of tyrosine results in the production of 3-nitrotyrosine which ultimately leading protein damage [69]. Presence of excessive ROS in the cells causes compromised energy production from mitochondria and has a possible damaging effect on mitochondrial and nuclear DNA [70]. Oxidative damages have detrimental effects on cellular processes, including membrane damage, metabolic failures and DNA alterations, all contributing to cell death [71].
Targeting calcium-mediated inter-organellar crosstalk in cardiac diseases
Published in Expert Opinion on Therapeutic Targets, 2022
Mohit M. Hulsurkar, Satadru K. Lahiri, Jason Karch, Meng C. Wang, Xander H.T. Wehrens
As the first barrier in the mitochondrial Ca2+ uptake, VDACs are involved in pathological Ca2+ signaling in mitochondria [112–114]. VDACs are associated with apoptotic Ca2+ signaling through interaction with pro- and anti-apoptotic proteins of the Bcl-2 family [128,130,131]. Increased interactions between Bcl-2 family members and the VDAC family of proteins are demonstrated in failing cardiomyocytes [132,133], suggesting that VDACs play a role in mitochondrial-dependent cell death. On the other hand, increased VDAC interaction with anti-apoptotic proteins like the hexokinases (HK), is protective during cardiac remodeling [134]. Therefore, inhibiting VDAC interaction with Bcl-2 or stabilizing its interaction with HKs could be an effective strategy to reduce cardiomyocyte deaths in ischemic cardiomyopathy. Additionally, 4-hydroxynonenal (4-HNE), a metabolite produced by the mitochondria and transported by the VDACs, is known to promote cardiac remodeling. Santin et al. recently showed that 4-HNE contributed to mitochondrial Ca2+ overload by interacting with VDACs [135]. Furthermore, targeting VDACs has been shown to have cardioprotective effects [136–141]. Since the metabolite and ion transport is regulated by channel gating, blocking the mitochondrial Ca2+ overload by targeting VDAC gating appears to be an effective strategy.