 Re: Oxidative Stress
> Oxidative stress and nutritional prevention
> in autoimmune rheumatic diseases
A role for the aryl hydrocarbon receptor and the dioxin TCDD in
rheumatoid arthritis.
OBJECTIVE: Environmental factors are involved in RA pathogenesis and
epidemiological studies have suggested that smoking is an
environmental risk factor for RA. The 2,3,7,8-tetrachlorodibenzo-p-
dioxin (TCDD) is one of the major toxic components in cigarettes. To
clarify the biological effects of smoking in RA, we investigated the
role of TCDD in RA pathogenesis. ...CONCLUSION: TNF-alpha activates
AhR expression in RA synovial tissue, and that cigarette smoking and
exposure to TCDD enhances RA inflammatory processes. TCDD induces
inflammatory cytokines via its association with AhR, resulting in
stimulation of the NF-kappaB and ERK signalling cascades. Thus TCDD
exposure, such as smoking exacerbates RA pathophysiology. PMID:
18617548
Polycyclic aromatic hydrocarbon increases mRNA level for interleukin 1
beta in human fibroblast-like synoviocyte line via aryl hydrocarbon
receptor.
Rheumatoid arthritis (RA) is characterized by proliferation of
synoviocytes that produce proinflammatory cytokines, which is
implicated in the pathogenesis of the disease ... Benzo[a]pyrene
(B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) also up-
regulated mRNA level of IL-1beta in the cells via AhR. As PAHs are
much contained in cigarette smoke, these findings provide the possible
basis for epidemiological studies indicating a strong association
between heavy cigarette smoking and outcome of RA. PMID: 14993811
Positive associations of serum concentration of polychlorinated
biphenyls or organochlorine pesticides with self-reported arthritis,
especially rheumatoid type, in women.
BACKGROUND: Persistent organic pollutants (POPs) can influence the
immune system, possibly increasing the risk of rheumatoid arthritis
(RA). In addition, as metabolic change due to obesity has been
proposed as one mechanism of osteoarthritis (OA), POPs stored in
adipose tissue may be also associated with OA. OBJECTIVE: Our goal in
this study was to examine associations of background exposure to POPs
with arthritis among the general population. DESIGN: We investigated
cross-sectional associations of serum POPs concentrations with the
prevalence of self-reported arthritis in 1,721 adults >/= 20 years of
age in the National Health and Nutrition Examination Survey
1999-2002. ...CONCLUSIONS: The possibility that background exposure to
PCBs may be involved in pathogenesis of arthritis, especially RA, in
women should be investigated in prospective studies.PMID: 17589595
Dioxin exposure and non-malignant health effects: a mortality study.
OBJECTIVE: To investigate, in a population heavily exposed to 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD), the possible unusual occurrence of
diseases other than cancer. METHODS: Five year extension of the follow
up of the cohort involved in the Seveso accident. Soil measurements
identified three exposure zones: (A) highest contamination, (B)
substantial, and (R) low but higher than background contamination.
Blood TCDD measurements, although limited in number, confirmed zone
exposure ranking. The 15 year mortality in the exposed cohort was
compared with that of a large population in the surrounding non-
contaminated territory. Relative risks (RRs) and 95% confidence
intervals (95% CIs) were estimated with Poisson regression techniques.
RESULTS: The already noted increased occurrence of cardiovascular
deaths was confirmed, in particular in zone A, among males for chronic
ischaemic heart disease (five deaths, RR 3.0, 95% CI 1.2 to 7.3), and
among females for hypertensive disease (three deaths, RR 3.6, 95% CI
1.2 to 11.4) and chronic RHEUMATIC heart disease. Novel findings were
the increase of chronic obstructive pulmonary disease, most notably
among males in zone A (four deaths, RR 3.7, 95% CI 1.4 to 9.9) and
females in zone B (seven deaths, RR 2.4, 95% CI 1.1 to 5.1); and from
diabetes, which was significantly increased in females in zone B (13
deaths, RR 1.9, 95% CI 1.1 to 3.2). In zone R, chronic ischaemic heart
disease (males and females), hypertension (females), and diabetes
(females) showed less pronounced, although significant excesses.
CONCLUSIONS: As well as high TCDD exposure, the accident caused a
severe burden of strain in the population. Both these factors might
have contributed to the noted increased risks (in particular,
circulatory and respiratory). The cardiovascular and immune toxicity
of TCDD, as well as its complex interaction with the endocrine system,
might be relevant to the explanations of these findings. These
results, although not conclusive, concur with previous data in
suggesting cardiopulmonary and endocrine effects in humans highly
exposed to TCDD. PMID: 9614398
Oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD).
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent
toxins and tumor promoters known to man. It is prototypical of many
halogenated polycyclic hydrocarbons that occur as environmental
contaminants. Pathologic lesions produced by these compounds are
mediated by an intracellular receptor protein called the TCDD (Ah)
receptor which functions as a trans-acting effector of gene
expression. However, the ultimate posttranslational pathways and
mechanisms involved in the expression of the toxic manifestations of
TCDD have received little attention and remain unclear, yet constitute
an important segment in our understanding of the overall mechanism of
action of TCDD. Recent studies have demonstrated that an oxidative
stress occurs in various tissues of TCDD-treated animals. Evidence
indicating production of an oxidative stress by TCDD in rodents is
reviewed and includes:enhanced in vitro and in vivo hepatic and
extrahepatic lipid peroxidation; increased hepatic and macrophage DNA
damage; increased urinary excretion of malondialdehyde; decreased
hepatic membrane fluidity; increased production of superoxide anion by
peritoneal macrophage; and decreased glutathione, nonprotein
sulfhydryl, and NADPH contents in liver. The potential role of
reactive oxygen species in tumor promotion by TCDD is discussed.
Possible sources and mechanisms of production of reactive oxygen
species in response to TCDD are considered in light of current
information. Evidence demonstrating the involvement of iron in TCDD-
induced formation of reactive oxygen species and DNA damage is
reviewed. Oxidative damage may contribute to many of the toxic
responses produced by TCDD and its bioisosteres, and may be common to
most of the tissue-damaging effects. PMID: 2210442
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