Free radical biology & medicine
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Free Radic. Biol. Med. · Oct 2016
Aescin reduces oxidative stress and provides neuroprotection in experimental traumatic spinal cord injury.
Aescin has many physiological functions that are highly relevant to spinal cord injury (SCI), including anti-inflammation, anti-oxidation, anti-oedema, and enhancing vascular tone. The present study investigated the putative therapeutic value of aescin in SCI, with a focus on its neuroprotective, anti-inflammatory, and anti-oxidative properties. Sodium aescinate (1.0mg/kg body weight) or equivalent volume of saline was administered 30min after injury by intravenous injection, with an additional dose daily for seven consecutive days after moderate SCI in rats. ⋯ The improved locomotor outcomes in aescin-treated rats corresponded to markedly decreased immune response, oxidative stress, neuronal loss, axon demyelination, spinal cord swelling, and cell apoptosis, measured around T8 after impact. Our data suggest aescin treatment as a novel, early, neuroprotective approach in SCI. Given the known safety of aescin in clinical applications, the results of this study suggest that it is a good candidate for SCI treatment in humans.
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Free Radic. Biol. Med. · Jul 2016
Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1α activation in hepatic ischemia/reperfusion injury.
Mitochondrial dysfunction, reactive oxygen species (ROS) production and oxidative stress during reperfusion are determinant in hepatic ischemia/reperfusion (I/R) injury but may be impacted by different anesthetic agents. Thus, we aimed at comparing the effects of inhaled sevoflurane or intravenous propofol anesthesia on liver mitochondria in a rodent model of hepatic I/R injury. To this, male Wistar rats underwent I/R surgery using sevoflurane or propofol. ⋯ In conclusion, hepatic I/R injury induces mitochondrial dysfunction that is not prevented by inhaled sevoflurane. On the contrary, propofol reduces liver damage and mitochondrial dysfunction by preserving respiratory activity, membrane potential and energy homeostasis, and limiting free radicals production as well as PTP opening. These hepatoprotective effects may involve the inhibition of HIF-1α.
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Free Radic. Biol. Med. · Apr 2016
Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy.
One of the most discomfortable dose-limiting adverse reactions of effective drugs for the treatment of solid tumors is a peripheral neuropathy which is the main reason for dose reduction and discontinuation of the therapy. We identified oxidative stress as one target of oxaliplatin toxicity in the search of possible adjuvant therapies to prevent neuropathy and alleviate pain. Therefore, we studied an effective SOD mimetic compound, MnL4, as a possible adjuvant treatment in in vitro cellular cultures and in vivo on a rat model of oxaliplatin-induced neuropathy. ⋯ Since MnL4 exerts its beneficial effects without interfering with the anticancer activity of oxaliplatin, it could be proposed as adjuvant to prevent and reduce oxaliplatin induced neuropathy.
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Free Radic. Biol. Med. · Mar 2016
Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1.
Familial Cerebral Cavernous Malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions. CCM lesions manifest across a range of different phenotypes, including wide differences in lesion number, size and susceptibility to intracerebral hemorrhage (ICH). Oxidative stress plays an important role in cerebrovascular disease pathogenesis, raising the possibility that inter-individual variability in genes related to oxidative stress may contribute to the phenotypic differences observed in CCM1 disease. Here, we investigated whether candidate oxidative stress-related cytochrome P450 (CYP) and matrix metalloproteinase (MMP) genetic markers grouped by superfamilies, families or genes, or analyzed individually influence the severity of CCM1 disease. ⋯ Overall, our candidate oxidative stress-related genetic markers set approach outlined CYP and MMP families and identified suggestive SNPs that may impact the severity of CCM1 disease, including the development of numerous and large CCM lesions and ICH. These novel genetic risk factors of prognostic value could serve as early objective predictors of disease outcome and might ultimately provide better options for disease prevention and treatment.
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Free Radic. Biol. Med. · Jan 2016
Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy.
The mitochondria are important sources of reactive oxygen species (ROS) in the heart. Mitochondrial ROS production has been implicated in the pathogenesis of diabetic cardiomyopathy, suggesting that therapeutic strategies specifically targeting mitochondrial ROS may have benefit in this disease. We investigated the therapeutic effects of mitochondria-targeted antioxidant mito-TEMPO on diabetic cardiomyopathy. ⋯ Therapeutic inhibition of mitochondrial ROS by mito-TEMPO reduced adverse cardiac changes and mitigated myocardial dysfunction in diabetic mice. Thus, mitochondria-targeted antioxidants may be an effective therapy for diabetic cardiac complications.