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Protective Effects of Liposomal N-Acetylcysteine against Paraquat-Induced Cytotoxicity and Gene Expression.

Mitsopoulos P, Suntres ZE - J Toxicol (2011)

Bottom Line: Attempts have been made to increase the antioxidant status in the lung using antioxidants (e.g., superoxide dismutase, vitamin E, N-acetylcysteine) but the outcome from such treatments is limited.In the present study, we compared the effectiveness of conventional N-acetylcysteine (NAC) and liposomal-NAC (L-NAC) against PQ-induced cytotoxicity and examined the mechanism(s) by which these antioxidant formulations conferred cytoprotection.Pretreatment of cells with L-NAC was significantly more effective than pretreatment with the conventional drug in reducing PQ-induced cytotoxicity, as indicated by the biomarkers used in this study.

View Article: PubMed Central - PubMed

Affiliation: Medical Sciences Division, Northern Ontario School of Medicine, Thunder Bay, ON, Canada P7B 5E1.

ABSTRACT
Paraquat (PQ) is a herbicide that preferentially accumulates in the lung and exerts its cytotoxicity via the generation of reactive oxygen species (ROS). There is no specific treatment for paraquat poisoning. Attempts have been made to increase the antioxidant status in the lung using antioxidants (e.g., superoxide dismutase, vitamin E, N-acetylcysteine) but the outcome from such treatments is limited. Encapsulation of antioxidants in liposomes improves their therapeutic potential against oxidant-induced lung damage because liposomes facilitate intracellular delivery and prolong the retention of entrapped agents inside the cell. In the present study, we compared the effectiveness of conventional N-acetylcysteine (NAC) and liposomal-NAC (L-NAC) against PQ-induced cytotoxicity and examined the mechanism(s) by which these antioxidant formulations conferred cytoprotection. The effects of NAC or L-NAC against PQ-induced cytotoxicity in A549 cells were assessed by measuring cellular PQ uptake, intracellular glutathione content, ROS levels, mitochondrial membrane potential, cellular gene expression, inflammatory cytokine release and cell viability. Pretreatment of cells with L-NAC was significantly more effective than pretreatment with the conventional drug in reducing PQ-induced cytotoxicity, as indicated by the biomarkers used in this study. Our results suggested that the delivery of NAC as a liposomal formulation improves its effectiveness in counteracting PQ-induced cytotoxicity.

No MeSH data available.


Related in: MedlinePlus

Effect of NAC or L-NAC pretreatment on the magnitude of gene expression in PQ-challenged cells.  RNA was extracted from cells challenged with 0 or 0.25 mM PQ for 4 h following pretreatment with 5.0 mM NAC- or L-NAC-containing media and analyzed via quantitative reverse-transcription PCR using a gene array.  The magnitude of expression of each gene is expressed on a scale ranging from minimal (intense green) to maximal (intense red) expression (n = 3 independent experiments).
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fig6: Effect of NAC or L-NAC pretreatment on the magnitude of gene expression in PQ-challenged cells. RNA was extracted from cells challenged with 0 or 0.25 mM PQ for 4 h following pretreatment with 5.0 mM NAC- or L-NAC-containing media and analyzed via quantitative reverse-transcription PCR using a gene array. The magnitude of expression of each gene is expressed on a scale ranging from minimal (intense green) to maximal (intense red) expression (n = 3 independent experiments).

Mentions: Changes in gene expression were assessed using a gene array designed to study genes involved with cellular stress and toxicity. The magnitude of gene expression in cells pretreated with NAC or L-NAC prior to 0.25 mM PQ challenge for 4 h was generally decreased relative to challenged cells with no pretreatment (Figure 6). Fold changes (relative to control cells) of each gene of the array following PQ challenge with no pretreatment, NAC pretreatment, or L-NAC pretreatment are listed in Table 1.


Protective Effects of Liposomal N-Acetylcysteine against Paraquat-Induced Cytotoxicity and Gene Expression.

Mitsopoulos P, Suntres ZE - J Toxicol (2011)

Effect of NAC or L-NAC pretreatment on the magnitude of gene expression in PQ-challenged cells.  RNA was extracted from cells challenged with 0 or 0.25 mM PQ for 4 h following pretreatment with 5.0 mM NAC- or L-NAC-containing media and analyzed via quantitative reverse-transcription PCR using a gene array.  The magnitude of expression of each gene is expressed on a scale ranging from minimal (intense green) to maximal (intense red) expression (n = 3 independent experiments).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3090768&req=5

fig6: Effect of NAC or L-NAC pretreatment on the magnitude of gene expression in PQ-challenged cells. RNA was extracted from cells challenged with 0 or 0.25 mM PQ for 4 h following pretreatment with 5.0 mM NAC- or L-NAC-containing media and analyzed via quantitative reverse-transcription PCR using a gene array. The magnitude of expression of each gene is expressed on a scale ranging from minimal (intense green) to maximal (intense red) expression (n = 3 independent experiments).
Mentions: Changes in gene expression were assessed using a gene array designed to study genes involved with cellular stress and toxicity. The magnitude of gene expression in cells pretreated with NAC or L-NAC prior to 0.25 mM PQ challenge for 4 h was generally decreased relative to challenged cells with no pretreatment (Figure 6). Fold changes (relative to control cells) of each gene of the array following PQ challenge with no pretreatment, NAC pretreatment, or L-NAC pretreatment are listed in Table 1.

Bottom Line: Attempts have been made to increase the antioxidant status in the lung using antioxidants (e.g., superoxide dismutase, vitamin E, N-acetylcysteine) but the outcome from such treatments is limited.In the present study, we compared the effectiveness of conventional N-acetylcysteine (NAC) and liposomal-NAC (L-NAC) against PQ-induced cytotoxicity and examined the mechanism(s) by which these antioxidant formulations conferred cytoprotection.Pretreatment of cells with L-NAC was significantly more effective than pretreatment with the conventional drug in reducing PQ-induced cytotoxicity, as indicated by the biomarkers used in this study.

View Article: PubMed Central - PubMed

Affiliation: Medical Sciences Division, Northern Ontario School of Medicine, Thunder Bay, ON, Canada P7B 5E1.

ABSTRACT
Paraquat (PQ) is a herbicide that preferentially accumulates in the lung and exerts its cytotoxicity via the generation of reactive oxygen species (ROS). There is no specific treatment for paraquat poisoning. Attempts have been made to increase the antioxidant status in the lung using antioxidants (e.g., superoxide dismutase, vitamin E, N-acetylcysteine) but the outcome from such treatments is limited. Encapsulation of antioxidants in liposomes improves their therapeutic potential against oxidant-induced lung damage because liposomes facilitate intracellular delivery and prolong the retention of entrapped agents inside the cell. In the present study, we compared the effectiveness of conventional N-acetylcysteine (NAC) and liposomal-NAC (L-NAC) against PQ-induced cytotoxicity and examined the mechanism(s) by which these antioxidant formulations conferred cytoprotection. The effects of NAC or L-NAC against PQ-induced cytotoxicity in A549 cells were assessed by measuring cellular PQ uptake, intracellular glutathione content, ROS levels, mitochondrial membrane potential, cellular gene expression, inflammatory cytokine release and cell viability. Pretreatment of cells with L-NAC was significantly more effective than pretreatment with the conventional drug in reducing PQ-induced cytotoxicity, as indicated by the biomarkers used in this study. Our results suggested that the delivery of NAC as a liposomal formulation improves its effectiveness in counteracting PQ-induced cytotoxicity.

No MeSH data available.


Related in: MedlinePlus