N-Acetylcysteine treatment to prevent the progression of multisystem organ failure

Molnár, Zsolt; Shearer, E.S.; Lowe, Derek

doi:10.1097/00003246-199906000-00028

Cited by 101 publications

(69 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clinical trials with antioxidants for acute illnesses, such as ALI or sepsis, have been disappointing, and no agent has been shown to be effective in critically ill patients (63)(64)(65)(66)(67)(68).…”

Section: Discussionmentioning

confidence: 99%

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Żmijewski¹,

Lorne²,

Zhao³

et al. 2009

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Although reactive oxygen species (ROS) are generally considered to be proinflammatory and to contribute to cellular and organ dysfunction when present in excessive amounts, there is evidence that specific ROS, particularly hydrogen peroxide (H 2 O 2 ), may have antiinflammatory properties. Objectives: To address the role that increases in intracellular H 2 O 2 may play in acute inflammatory processes, we examined the effects of catalase inhibition or the absence of catalase on LPS-induced inflammatory responses. Methods: Neutrophils from control or acatalasemic mice, or control neutrophils incubated with the catalase inhibitor aminotriazole, were treated with LPS, and levels of reactive oxygen species, proteasomal activity, NF-kB activation, and proinflammatory cytokine expression were measured. Acute lung injury (ALI) was produced by intratracheal injection of LPS into control, acatalasemic-, or aminotriazole-treated mice. Measurements and Main Results: Intracellular levels of H 2 O 2 were increased in acatalasemic neutrophils and in neutrophils exposed to aminotriazole. Compared with LPS-stimulated neutrophils from control mice, neutrophils from acatalasemic mice or neutrophils treated with aminotriazole demonstrated reduced 20S and 26S proteasomal activity, IkB-a degradation, NF-kB nuclear accumulation, and production of the proinflammatory cytokines TNF-a and macrophage inhibitory protein (MIP)-2. The severity of LPS-induced ALI was less in acatalasemic mice and in mice treated with aminotriazole as compared with that found in control mice. Conclusions: These results indicate that H 2 O 2 has antiinflammatory effects on neutrophil activation and inflammatory processes, such as ALI, in which activated neutrophils play a major role.

show abstract

Section: Discussionmentioning

confidence: 99%

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Żmijewski¹,

Lorne²,

Zhao³

et al. 2009

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…30 min before administration of MAP and a subsequent continuous infusion of NAC (12 mg/kg/h, i.v.) over 8.5 h, with a slight modification of the method reported previously (Molnar et al, 1999;Rank et al, 2000) (Figure 1). …”

Section: Drug Administrationmentioning

confidence: 98%

Protective Effects of N-acetyl-L-cysteine on the Reduction of Dopamine Transporters in the Striatum of Monkeys Treated with Methamphetamine

Hashimoto

Tsukada

Nishiyama

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Several lines of evidence suggest that oxidative stress might contribute to neurotoxicity in the dopaminergic nerve terminals after administration of methamphetamine (MAP). We undertook the present study to determine whether intravenous administration of N-acetyl-L-cysteine (NAC), a potent antioxidant drug, could attenuate the reduction of dopamine transporter (DAT) in the striatum of monkey brain after administration of MAP. Positron emission tomography studies demonstrated that repeated administration of MAP (2 mg/kg as a salt, four times at 2-h intervals) significantly decreased the accumulation of radioactivity in the striatum after intravenous administration of [ 11 C]b-CFT. In contrast, the binding of [ 11 C]SCH 23390 to dopamine D 1 receptors in the monkey striatum was not altered after the administration of MAP. A bolus injection of NAC (150 mg/kg, i.v.) 30 min before MAP administration and a subsequent continuous infusion of NAC (12 mg/kg/h, i.v.) over 8.5 h significantly attenuated the reduction of DAT in the monkey striatum 3 weeks after the administration of MAP. These results suggest that NAC could attenuate the reduction of DAT in the monkey striatum after repeated administration of MAP. Therefore, it is likely that NAC would be a suitable drug for treatment of neurotoxicity in dopaminergic nerve terminals related to chronic use of MAP in humans.

show abstract

“…It must be considered, though, that especially IV NAC may be harmful, leading to allergic reactions [247] or decreased cardiac output or survival in patients with septic shock [248,249].…”

Section: Rationalementioning

confidence: 99%

Prevention of acute kidney injury and protection of renal function in the intensive care unit

et al. 2009

View full text Add to dashboard Cite

Background: Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. Objectives: To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. Method: A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Conclusions and recommendations: Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood Intensive Care Med (2010) 36:392-411 DOI 10.1007/s00134-009-1678 EXPERT PANEL pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention.

show abstract

N-Acetylcysteine treatment to prevent the progression of multisystem organ failure

Cited by 101 publications

References 29 publications

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Protective Effects of N-acetyl-L-cysteine on the Reduction of Dopamine Transporters in the Striatum of Monkeys Treated with Methamphetamine

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Contact Info

Product

Resources

About