Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

Abstract

Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg·day) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg·day ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloproteinase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation. NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review

“…93 ROS generation is the initial step in brain damage after cerebral ischemia/reperfusion. 115 ROS induce oxidative stress by activating several signaling pathways and react with and cause damage to lipids, proteins, and DNA. 116,117 Nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) are essential for maintaining the intracellular balance between the generation of ROS (which ensures a reductive environment for cellular activities) and neutralization (which maintains energy homeostasis).…”

Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells

“…It has been reported that mito‐T is a potent mitochondria‐targeted antioxidant, which could act in ischemic tissues linked with hypoxia‐induced oxidative stress (Ding, Liu, Bi, & Zhang, 2017; Du et al, 2019; Du, Farhood, & Jaeschke, 2017; Li et al, 2018; Liu, Wang, Ding, & Wang, 2018; Nautiyal, Shaltout, Chappell, & Diz, 2019; Shetty, Kumar, & Bharati, 2019; Yang et al, 2018; Zhan et al, 2018). In the present study, mito‐T, a mitochondria‐targeted superoxide dismutase mimetic, dramatically reduced AMA‐induced mitochondrial oxidative stress, and thus effectively protected MSCs.…”

“…It has been reported that mito-T is a potent mitochondriatargeted antioxidant, which could act in ischemic tissues linked with hypoxia-induced oxidative stress (Ding, Liu, Bi, & Zhang, 2017;Du et al, 2019;Du, Farhood, & Jaeschke, 2017;Li et al, 2018;Liu, Wang, Ding, & Wang, 2018;Nautiyal, Shaltout, Chappell, & Diz, 2019;Shetty, Kumar, & Bharati, 2019;Yang et al, 2018;Zhan et al, 2018).…”

Mito-TEMPO improved L-Arginine- induced acute pancreatitis in rats via TLR-4/ NF-кB/ NLRP3 inflammasome downregulation and antioxidant properties

“…Group 3 (L-Arginine +Mito-TEMPO treated) received 0.7mg/kg body weight/ day, i.p. for 7 days started 24 hours after L-arginine injection 27,28 .…”

“…The tempo is a mimetic superoxide dismutase that in the catalytic cycle dismutases superoxide, while TPP is a membrane-permeant cation that accumulates several hundred folds inside the membrane potential driven mitochondria. This combination produces an effect-targeted mitochondrial chemical 26,27 .…”