Agomelatine ameliorates cadmium-induced toxicity through the modification of HMGB-1/TLR-4/NFκB pathway

Hafez, Heba M.; Waz, Shaimaa; El‐Tahawy, Nashwa Fathy Gamal; Mohamed, Mervat Z.

doi:10.1016/j.taap.2022.116313

Cited by 7 publications

(2 citation statements)

References 72 publications

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“…In the present study, our molecular and immunohistochemical findings revealed that the Cd-intoxicated group markedly upregulates the expression level of HSP70, TLR4, and NF-κB. These findings come in agreement with [123] who reported that Cd significantly promoted the expression level of the TLR4/NF-κB pathway in duck embryo hepatocytes, and also [124], exhibited that Cd enhanced the expression of HMGB1 downstream mediators, including TLR-4 and NF-κB which exacerbated the damaging effects of Cd in exposed tissues via stimulating the release of several inflammatory cytokines. Interestingly [125], revealed that Cd could induce adrenal damage through activation of TLR4/ NF-κB-mediated inflammatory responses which play an essential role in Cd-induced toxic lesions.…”

Section: Discussionsupporting

confidence: 92%

Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers’ Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway

Abomosallam,

Hendam,

Shouman

et al. 2024

Biol Trace Elem Res

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Cadmium (Cd) is a serious environmental pollutant affecting various tissues/organs in broilers and compromising their immunological function and productivity. Therefore, the current study aimed to investigate Cd-induced immunotoxicity and potential immunoprotective effect of rutin nanoparticles (RNPs) in the bursal tissue of broilers. A total number of 150 chicks from the Hubbard breed were randomly divided into 5 groups. Group I was fed on standard basal diet (SD) with normal drinking water (DW), Group II received SD containing RNPs (50 mg/kg feed) with DW, Group III fed on SD and DW containing Cd (150 mg/L), Group IV co-treated with rutin-enforced SD (50 mg/kg diet) and DW containing Cd (150 mg/L), and finally, Group V co-supplemented with RNP-enhanced SD (50 mg/kg diet) DW containing Cd (150 mg/L). Productive performance, economic efficiency, oxidative biomarkers, histopathological changes, and the expression level of TLR-4, HSP-70, caspase 3, NF-κB, Bcl-2, and Bax were assessed in the BF tissue. Cd led to severe production and economic losses in exposed birds with a marked surge of oxidative biomarkers, pro-inflammatory cytokines, and histopathological changes in the bursal tissue which could be explained through upregulation of the Hsp70/TLR4/NF-κB molecular pathway in the BF tissue. Meanwhile, RNPs could alleviate most of these changes and prevail optimistic immunomodulatory properties which subsequently could enhance broilers’ productivity when incorporated in their diets. Graphical Abstract

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Section: Discussionsupporting

confidence: 92%

Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers’ Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway

Abomosallam,

Hendam,

Shouman

et al. 2024

Biol Trace Elem Res

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“…AGM has anticancer, antioxidant, anti-inflammatory, and anti-apoptotic effects [11]. It also has neuroprotective, hepatoprotective, cardioprotective, and testicular-protective properties [11][12][13]. It is a melatonin analog that is now used to treat depression and sleep disorders.…”

Section: Introductionmentioning

confidence: 99%

Agomelatine protects hippocampal neurons against doxorubicin induced toxicity

Betul Danısman,

Betul Cicek

2023

GSC Biol. Pharm. Sci.

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Doxorubicin (DOX) is a powerful chemotherapy drug used in numerous cancer treatments, known to causes neurotoxicity and impair cognitive function in cancer patients. The main mechanism thought to be responsible for the neuronal damage related to chemotherapy is oxidative stress. Agomelatine (AGM) has recently been identified as a neuroprotective agent against toxicity and the effect of AGM on DOX-induced neurotoxicity was investigated in this study. In order to evaluate the effect of AGM on oxidative stress and apoptosis, malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and Caspase-3 expression were analyzed in the HT-22 cell line. AGM considerably reduced oxidative damage due to DOX in vitro. MDA and Caspase-3 were considerably higher in the DOX group. These values were dramatically decreased by AGM. AGM greatly increased the CAT and SOD levels when compared to the DOX group. These results suggest that DOX therapy alters antioxidant status in hippocampus, a critical cognition-related region. So if we are aware of the functional effects of DOX, it is possible to avoid some of the disabling side effects of chemotherapy in cancer patients and may prevent these effects with antioxidant agents such as AGM

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Adverse effects of cadmium on lymphoid organs, immune cells, and immunological responses

Kumari,

Nanda,

Firdaus

2024

J of Applied Toxicology

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Humans and animals possess robust immune systems to safeguard against foreign pathogens. However, recent reports suggest a greater incidence of immunity breakdown due to exposure to environmental pollutants, with heavy metals emerging as potential candidates in such immuno‐toxicological studies. While we have extensive data on the general toxicity resulting from exposure to heavy metals, comprehensive documentation of their role as immune disruptors remains scarce. Cd (Cadmium) exerts immunomodulation by interfering with immune organs and cells, leading to altered structure, physiology, and function, thereby inducing symptoms of immune deregulation, inflammation and/or autoimmunity.This review aims to summarize the link between Cd exposure and immune dysfunction, drawing from case studies on exposed human subjects, as well as research conducted on various model organisms and in‐vitro culture systems.

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Agomelatine ameliorates cadmium-induced toxicity through the modification of HMGB-1/TLR-4/NFκB pathway

Cited by 7 publications

References 72 publications

Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers’ Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway

Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers’ Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway

Agomelatine protects hippocampal neurons against doxorubicin induced toxicity

Adverse effects of cadmium on lymphoid organs, immune cells, and immunological responses

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