1.Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.
Jelena KULAS ; Marina NINKOV ; Dina TUCOVIC ; Aleksandra POPOV ALEKSANDROV ; Mirela UKROPINA ; Maja CAKIC MILOSEVIC ; Jelena MUTIC ; Milena KATARANOVSKI ; Ivana MIKROV
Biomedical and Environmental Sciences 2019;32(7):508-519
OBJECTIVE:
The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response.
METHODS:
Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated.
RESULTS:
Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro.
CONCLUSION
The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.
Administration, Oral
;
Animals
;
Cadmium
;
administration & dosage
;
toxicity
;
Leukocytes
;
metabolism
;
Lung
;
drug effects
;
immunology
;
pathology
;
Male
;
Rats
;
Staphylococcus epidermidis
;
Toxicity Tests, Subchronic
2.Oral Cadmium Intake Enhances Contact Allergen-induced Skin Reaction in Rats.
Dina TUCOVIC ; Jelena KULAS ; Ivana MIRKOV ; Dusanka POPOVIC ; Lidija ZOLOTAREVSKI ; Marta DESPOTOVIC ; Milena KATARANOVSKI ; Popov Aleksandrov ALEKSANDRA
Biomedical and Environmental Sciences 2022;35(11):1038-1050
OBJECTIVE:
The effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including the skin, in which it disturbs homeostasis, thus resulting in inflammation and injury.
METHODS:
Male rats were evoked with experimental contact hypersensitivity reaction (CHS) to hapten dinitrochlorobenzene (DNCB), after prolonged (30 day) oral exposure to an environmentally relevant Cd dose (5 ppm). The ear cell population was analyzed with flow cytometry. Cytokine production by ear skin cells and the activity of skin-draining lymph node (DLN) cells were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS:
Orally acquired Cd (5 ppm) increased CHS intensity only in Dark Agouti (DA) rats by affecting inflammatory responses in both the sensitization (an increase of IFN-γ and IL-17 cytokine production) and challenge (an increase of CD8 + and CD4 + cell number and TNF, IFN-γ and IL-17 cytokine production) phases. An increased CHS reaction was seen in Albino Oxford (AO) rats only at a high Cd dose (50 ppm), during the challenge phase (an increase of CD8 + and CD4 + cell number and TNF, IFN-γ and IL-17 cytokine production).
CONCLUSION
These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.
Male
;
Rats
;
Animals
;
Allergens/toxicity*
;
Cadmium/toxicity*
;
Dinitrochlorobenzene/toxicity*
;
Interleukin-17
;
Cytokines
3.Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium.
Jelena KULAS ; Dina TUCOVIC ; Milica ZELJKOVIC ; Dusanka POPOVIC ; Aleksandra POPOV ALEKSANDROV ; Milena KATARANOVSKI ; Ivana MIRKOV
Biomedical and Environmental Sciences 2021;34(3):192-202
Objective:
To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd).
Methods:
The effect of Cd on AhR activation (
Results:
Cd increased
Conclusion
AhR signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd. The relevance of the AhR to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.
Animals
;
Basic Helix-Loop-Helix Transcription Factors/immunology*
;
Cadmium/toxicity*
;
Cytochrome P-450 CYP1A1/immunology*
;
Cytochrome P-450 CYP1B1/immunology*
;
Cytokines/immunology*
;
Environmental Pollutants/toxicity*
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Male
;
Rats
;
Receptors, Aryl Hydrocarbon/immunology*