Free radical biology & medicine
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Morphine treatment for 5 days protects heart against ischemia-reperfusion (IR) injury. This study evaluated the involvement of nitric oxide (NO) in morphine-induced renal protection. Three weeks after right nephrectomy, increasing doses of morphine were administered (20-30 mg kg(-1)day(-1), 5 days) to develop dependence in rats. ⋯ NO production was not decreased during the withdrawal period (p>0.1 vs morphine dependence+IR group). Morphine dependence provided renal protection in the acute phase and during withdrawal. Excessive increase or decrease in NO production abolished the effects of morphine, which suggested a role for balanced NO production and iNOS expression.
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Free Radic. Biol. Med. · May 2010
Redox-mediated reciprocal regulation of SERCA and Na+-Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes.
Myocardial failure is associated with increased oxidative stress and abnormal excitation-contraction coupling characterized by depletion of sarcoplasmic reticulum (SR) Ca(2+) stores and a reduction in Ca(2+)-transient amplitude. Little is known about the mechanisms whereby oxidative stress affects Ca(2+) handling and contractile function; however, reactive thiols may be involved. We used an in vitro cardiomyocyte system to test the hypothesis that short-term oxidative stress induces SR Ca(2+) depletion via redox-mediated regulation of sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) and the sodium-Ca(2+) exchanger (NCX) and that this is associated with thiol oxidation. ⋯ Pretreatment with the NCX inhibitor KB-R7943 before H(2)O(2) increased diastolic [Ca(2+)](i) and mimicked the effect of SERCA inhibition with thapsigargin. These functional effects were associated with oxidative modification of thiols on both SERCA and NCX. In conclusion, redox-mediated SR Ca(2+) depletion involves reciprocal regulation of SERCA and NCX, possibly via direct oxidative modification of both proteins.
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Free Radic. Biol. Med. · Feb 2010
Inhibition of SREBP-1c-mediated hepatic steatosis and oxidative stress by sauchinone, an AMPK-activating lignan in Saururus chinensis.
Sauchinone, as an AMP-activated kinase (AMPK)-activating lignan in Saururus chinensis, has been shown to prevent iron-induced oxidative stress and liver injury. Sterol regulatory element binding protein-1c (SREBP-1c) plays a key role in hepatic steatosis, which promotes oxidative stress in obese subjects. Previously, we identified the role of AMPK in liver X receptor-alpha (LXRalpha)-mediated SREBP-1c-dependent lipogenesis. ⋯ Also, sauchinone had the ability to inhibit oxidative stress as shown by decreases in thiobarbituric acid-reactive substance formation, nitrotyrosinylation, and 4-hydroxynonenal production. Moreover, it prevented not only the liver injury, but also the AMPK inhibition elicited by HFD feeding. These results demonstrate that sauchinone has the capability to inhibit LXRalpha-mediated SREBP-1c induction and SREBP-1c-dependent hepatic steatosis, thereby protecting hepatocytes from oxidative stress induced by fat accumulation.
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Free Radic. Biol. Med. · Jan 2010
Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation.
The free radical theory of aging is currently one of the most popular. In parallel, many studies have demonstrated the association of fibrosis and increased oxidative stress in the pathogenesis of some chronic human diseases, and fibrosis is often characteristic of aging tissues. One of the few interventions that effectively slow aging is calorie restriction and the protection against the age-associated increase of oxidative stress remains one of the foremost hypotheses to explain this action. ⋯ In parallel there was a significant increase in inflammatory cytokine levels and in NF-kB DNA binding activity with advancing age. Alternate-day fasting protected against all these age-related phenomena. These data support the hypothesis that this kind of dietary restriction protects against age-related fibrosis, at least in part by reducing inflammation and oxidative damage, and this protection can thus be considered a factor in the prevention of age-related diseases with sclerotic evolution.
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Free Radic. Biol. Med. · Dec 2009
ReviewA systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome.
Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality in the intensive care unit. Recently mitochondrial dysfunction has been proposed as a key early cellular event in critical illness. A growing body of experimental evidence suggests that mitochondrial therapies are effective in sepsis and MODS. ⋯ A substantial body of evidence from experimental studies at both the cellular and the organ level suggests a beneficial role for the administration of mitochondrial therapies in sepsis and MODS. We expect that mitochondrial therapies will have an increasingly important role in the management of sepsis and MODS. Clinical trials are now required.