Increased Cerebrospinal Fluid and Serum Nitrite and Nitrate Levels in Amyotrophic Lateral Sclerosis

Taşkıran, Dilek; Sağduyu, Ayşe; Yuceyar, N; Kutay, Fatma Z.; Pöğün, Şakire

doi:10.3109/00207450008986493

Cited by 33 publications

(17 citation statements)

References 21 publications

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“…The increased level of NO oxidation products may contribute to the pathophysiology of HAT (6) and other disorders of the central nervous system such as bacterial meningitis (17,34), cerebral systemic lupus erythematosus (4), and amyotrophic lateral sclerosis (29). Furthermore, NOS-II has also been found in macrophages in multiple sclerosis plaques (8) and in the brain lesions of mice chronically infected with T. b. brucei (15).…”

Section: Discussionmentioning

confidence: 99%

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

Mamani-Matsuda¹,

Rambert²,

Malvy

et al. 2004

Antimicrob Agents Chemother

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In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-␣ and nitric oxide derivatives. In the present study, quercetin (3,3,4,5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-␣ and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.Human African trypanosomiasis (HAT), or sleeping sickness, is provoked by the inoculation of Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense into humans by a tse-tse fly. HAT is considered a reemerging disease, mainly due to the deterioration of health facilities in endemic areas. Blood monocytes and tissue macrophages play a key role in the control of parasite numbers, and an increased number of activated hematopoietic cells are observed during trypanosomiasis (33). Trypanosome-derived products were also shown to activate the generation by macrophages of various proinflammatory mediators including tumor necrosis factor alpha (TNF-␣), nitric oxide (NO), and interleukin-1 (IL-1) (7,19,28). TNF-␣ and NO fulfill important functions in host-parasite interactions as they control infections by various pathogens, including T. b. gambiense (6,21,32). In addition, chronic secretion of macrophage-derived mediators is in part responsible for the pathogenic aspects of HAT (18,20,25,27). Accordingly, a correlation can be made between high levels in serum of TNF-␣ and disease severity in HAT (25), and successful treatment with melarsoprol significantly reduced the circulating concentration of this cytokine in HAT patients (27).Only a few drugs are available to treat HAT, and some of them are effective only during the first phase of disease or are difficult to administer because of their high toxicity. These facts led us to investigate the effects of nutrition-derived flavonoids on in vitro interactions between T. b. gambiense and human leukocytes. Flavonoids are produced in plants in response to environmental stress such as adverse weather or attacks by insects, animals, or pathogens (37). For humans, the main flavonoid dietary sources are fruits, beverages, vegetables, dry legumes, and cereals. Recently, various purified polyphenolic compounds were defined as strong free-radical scavenging agents that display antitumoral, antimicrobial, and anti-inflammatory activities (3).Quercetin and its derivatives are among the most common polyphenolic flavonoids present in plants such as onions, ginkgo biloba, and tea ...

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Section: Discussionmentioning

confidence: 99%

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

Mamani-Matsuda¹,

Rambert²,

Malvy

et al. 2004

Antimicrob Agents Chemother

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“…Nitrite and nitrate levels were measured as described earlier [26]. Briefly nitrite levels were quantified by colorimetric assay based on the Griess reaction [27].…”

Section: Nitric Oxide Assaymentioning

confidence: 99%

Elevated Inflammatory Markers in a Group of Amyotrophic Lateral Sclerosis Patients from Northern India

et al. 2008

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The role of cytokines in the pathophysiology of amyotrophic lateral sclerosis (ALS) and its relation to clinical outcome has not been clearly defined. We evaluated tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and nitric oxide (NO) levels in the serum of 22 ALS patients and 20 controls. Serum TNF-alpha levels and IFN-gamma levels were significantly (P < 0.001) elevated in ALS patients. We also observed NO levels to be significantly (P < 0.05) increased with respect to normal subjects. We further noticed positive correlation between the duration of ALS and these proinflammatory molecule levels. Exitotoxicity and oxidative stress are known to play a crucial role in the neurodegeneration observed in ALS. Since high levels of TNF-alpha are known to be cytotoxic, it could be that a complex interplay of these effectors may be one of the factors underlying the progression of ALS. This study confirms the involvement of inflammation in ALS and the need to develop surrogate markers to check the progression of this disease.

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“…For example, while disturbed reuptake of Glu may underline some neurological disorders such as amyotrophic lateral sclerosis (ALS), inhibition of Glu uptake may also facilitate learning and memory processes (Rothstein, 1995). On the other hand, regulating dopaminergic neurotransmission by reuptake may affect reward systems or motor control with substantial influences in addictive or locomotor behavior, respectively (Taskiran et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Effect of Carbon Monoxide on Dopamine and Glutamate Uptake and cGMP Levels in Rat Brain

Taşkıran

Kutay

Pöğün

2002

Neuropsychopharmacol

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After the recognition of nitric oxide (NO) as a messenger molecule in the nervous system, carbon monoxide (CO) has received attention with similar properties. The present study aims to elucidate the effects of CO on synaptosomal dopamine ( 3 H-DA) and glutamate ( 3 H-Glu) uptake and on cGMP levels; possible interaction between NO and CO systems was also evaluated. Our results provide evidence for the inhibition of DA and Glu uptake by CO in a time-, dose-, and temperature-dependent manner in rat striatum and hippocampus, respectively; the inhibition observed was sexually dimorphic with more pronounced effects in females. Basal cGMP levels were higher in female rats than males in the striatum and exogenous CO increased striatal cGMP levels only in males; no effect of CO was observed in the hippocampus. In vivo nitric oxide synthase (NOS) inhibition increased DA and Glu uptake; however, CO was still effective in inhibiting uptake following NOS inhibiton. Taken together, these findings suggest a role for CO in trans-synaptic regulation through modulation of DA and Glu transporters and of cGMP levels; the effect on cGMP levels is independent of NOS activity and appears to be sexually dimorphic and region specific.

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Increased Cerebrospinal Fluid and Serum Nitrite and Nitrate Levels in Amyotrophic Lateral Sclerosis

Cited by 33 publications

References 21 publications

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

Elevated Inflammatory Markers in a Group of Amyotrophic Lateral Sclerosis Patients from Northern India

Effect of Carbon Monoxide on Dopamine and Glutamate Uptake and cGMP Levels in Rat Brain

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