Nitroxidative Stress, Cell—Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2050 - 2050

Published: Feb. 26, 2025

Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative nitrosative stress, an imbalance between reactive oxygen nitrogen species (ROS/RNS) antioxidant defenses, plays crucial role in its pathophysiology. While are essential for physiological functions, excessive levels can cause cellular component neuronal dysfunction pain. This review highlights the complex interactions species, systems, cell signaling, neuropathic We discuss roles ROS/RNS detrimental effects oxidative stress. Furthermore, we explore potential manganese porphyrins, compounds with properties, as promising therapeutic agents mitigate stress alleviate pain by targeting key pathways involved Further research is needed fully understand their managing human non-human animals.

Language: Английский

Polydatin attenuates Alzheimer’s disease induced by aluminum chloride in rats: evidence for its antioxidant and anti-inflammatory effects

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Considering the complex pathophysiological mechanisms behind Alzheimer's disease (AD), a few drugs for managing related cognitive symptoms have been approved. The phytochemical resveratrol has shown promising anti-inflammatory and antioxidant effects in AD, but it low bioavailability. Chemical modification of to its glycosylated form, polydatin (PD), significantly increases bioavailability bioactivity. study aimed investigate therapeutic potential action PD against AD rats. was caused by an intraperitoneal (i.p.) administration aluminum chloride (AlCl3). Six groups six rats each were defined as sham, negative control (AlCl3), positive (Donepezil), treatments (PD 5, 10, 20 mg/kg, i.p.). On days 7, 8, 14, 15, rats' behavioral changes assessed open field, Y-maze test, passive avoidance elevated plus maze tests. At end study, blood samples collected assess levels glutathione (GSH), catalase (CAT), nitrite, well activity matrix metalloproteinases (MMPs). Furthermore, hippocampal brain tissue removed used histological investigations. findings revealed that injections at three different doses (5, mg/kg) improved other impairments. capacity increasing GSH CAT while decreasing serum nitrite levels. showed reducing inflammatory MMP-9, elevating MMP-2. also modulated pathogenic tissue. alleviated impairments enhancing defenses neuroinflammation.

Language: Английский

Deciphering the antinociceptive and anti-inflammatory effects of pelargonidin through L-arginine/nitric oxide/cyclic GMP/ATP-sensitive potassium channel signaling pathway and gamma-aminobutyric acid/opioidergic receptors

Behavioural Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

There are complex dysregulated pathways behind the pathogenesis of pain and inflammation. Because most present drugs have certain side effects or not effective enough, providing novel multitargeting potent therapeutic agents is particular importance. This study investigates antinociceptive pelargonidin, an anthocyanin derived from various plants, through modulation L-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/ATP-sensitive potassium channel (KATP) signaling pathway. We also evaluated anti-inflammatory role pelargonidin passing gamma-aminobutyric acid (GABA) opioidergic receptors. Two experimental models were utilized. In carrageenan model, 42 rats divided into control, diclofenac, three doses (3, 6, 9 mg/kg). addition, two groups received mg/kg + naloxone flumazenil. For formalin 90 male mice assigned to 10 receiving L-arginine, S-nitroso-N-acetylpenicillamine (SNAP), N(gamma)-nitro-L-arginine methyl ester (L-NAME), glibenclamide, sildenafil individually alongside mg/kg. Our results indicated that significantly decreased inflammation in a dose-dependent manner. Notably, flumazenil diminished pelargonidin's effectiveness, underscoring significant these Mechanistically, it was shown mediated by NO While L-NAME glibenclamide reduced efficacy, supplementation with SNAP enhanced effect. investigation demonstrated possesses actions L-arginine/NO/cGMP/KATP pathways, GABA receptors, respectively.

Language: Английский