Oxidative Stress in a Model of Toxic Demyelination in Rat Brain: The Effect of Piracetam and Vinpocetine

Abstract

ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

“…In agreement with this, we showed vinpocetine to also inhibit the carrageenan-induced peripheral decrease in antioxidant capacity and GSH levels. Previous work, in a rat demyelination model, showed vinpocetine to reduce oxidative stress [ 12 ], although, the association of oxidative stress with increased pro-inflammatory cytokines was not addressed in this study. Considering the dependency of carrageenan-induced hyperalgesia on not only TNF-α and IL-1β production [ 33 ], but also oxidative stress [ 35 , 62 ], and the peripheral inhibition of these cytokines and oxidative stress by vinpocetine treatment reported here, our results serve to better integrate previous work that separately described the analgesic, anti-inflammatory and antioxidant effects of vinpocetine [ 9 , 11 , 12 , 20 , 21 , 45 – 47 ].…”

“…One important step during inflammation-triggered hyperalgesia is increased intracellular calcium levels in nociceptors [ 75 ], which vinpocetine may achieve by reducing sodium currents-induced intracellular calcium level increases, as shown by previous data in rat hippocampal pyramidal cells [ 76 ]. Moreover, systemic treatment with vinpocetine delays the reaction time of naïve mice in the hot plate test [ 20 ] and reduces oxidative stress levels in rat brain [ 12 ], suggesting that supraspinal mechanisms are also involved. Such data is in concordance with the more pronounced effects of vinpocetine to reduce thermal hyperalgesia, as reported here.…”

“…As well as being a phosphodiasterase-1 inhibitor [ 8 ], the emerging literature suggests that vinpocetine also has potent anti-inflammatory effects via phosphodiasterase-1-independent inhibition of nuclear factor kappa B (NF-κB) signaling and the production of pro-inflammatory cytokines, such as IL-1β and TNF-α [ 9 ]. Moreover, it has been shown that vinpocetine inhibits neuronal reactive oxygen species (ROS) production [ 10 , 11 ], thereby decreasing oxidative stress [ 12 ]. The pro-inflammatory cytokines TNF-α and IL-1β, in conjunction with ROS, such as the superoxide anion radical, are important peripheral and spinal hyperalgesic mediators and therefore represent relevant targets for analgesic drug development [ 13 , 14 ].…”

Liver proteome alterations in psychologically distressed rats and a nootropic drug

“…It is well known that piracetam protects neuronal cells against oxidative stress ( Verma et al, 2018 ), increases mitochondrial membrane fluidity and ATP production ( Müller et al, 1997 ), and improves the mitochondrial membrane potential ( Keil et al, 2006 ; Kurz et al, 2010 ), as well as the glucose uptake and utilization ( Abdel-Salam et al, 2013 ; Pandey & Garabadu, 2016 ), making this drug a metabolic enhancer and a neuroprotector. Thus, in animal and human studies, piracetam protected the brain against memory and cognitive function impairments induced by physical and chemical agents or by age ( Kessler et al, 2000 ; Holinski et al, 2008 ; Gupta et al, 2009 ; Leuner et al, 2010 ; Abdel-Salam et al, 2011 ; Kosta et al, 2011 ; Muley et al, 2013 ; Wang, Li & Chen, 2016 ) and improved cognition and working memory in healthy volunteers ( Alkuraishy et al, 2014 ). In a previous study, we also evidenced the anxiolytic effect and the protective role of this drug against lipid peroxidation in circulating mononuclear cells in rats subjected to psychological distress ( Grigoruţă et al, 2018 ).…”

Preconditioning with PDE1 Inhibitors and Moderate-Intensity Training Positively Affect Systemic Redox State of Rats

“…Interestingly, in the case of vinpocetine, with the higher dose of vinpocetine, the increment in GSH was less apparent in the hippocampus and striatum. An intriguing explanation for these observations is that at its high concentration, vinpocetine exhibit prooxidant properties and increase free radical production or act as a free radical [50]. As mentioned above, GSH is responsible for lowering the H 2 O 2 level.…”