Toxicity Mechanisms, Exposure, Toxicokinetic and Risk Assessment Aspects of Metals, Toxic for Animals and Humans, Volume II

24.9K
views
79
authors
10
articles
Editors
6
Impact
Loading...
Original Research
11 August 2022

Cadmium (Cd) is a toxic heavy metal extensively used in industrial and agricultural production. Among the main mechanisms of Cd-induced liver damage is oxidative stress. Quercetin (QE) is a natural antioxidant. Herein, the protective effect of QE on Cd-induced hepatocyte injury was investigated. BRL-3A cells were treated with 12.5 μmol/L CdCl2 and/or 5 μmol/L QE for 24 h. The cells and medium supernatant were collected, and the ALT, AST, and LDH contents of the medium supernatant were detected. The activities or contents of SOD, CAT, GSH, and MDA in cells were determined. Intracellular ROS levels were examined by flow cytometry. Apoptosis rate and mitochondrial-membrane potential (ΔΨm) were detected by Hoechst 33,258 and JC-1 methods, respectively. The mRNA and protein expression levels of Nrf2, NQO1, Keap1, CytC, caspase-9, caspase-3, Bax, and Bcl-2 were determined by real-time PCR (RT-PCR) and Western blot methods. Results showed that Cd exposure injured BRL-3A cells, the activity of antioxidant enzymes decreased and the cell ROS level increased, whereas the ΔΨm decreased, and the expression of apoptotic genes increased. Cd inhibited the Nrf2-Keap1 pathway, decreased Nrf2 and NQO1, or increased Keap1 mRNA and protein expression. Through the combined action of Cd and QE, QE activated the Nrf2-Keap1 pathway. Consequently, antioxidant-enzyme activity decreased, cellular ROS level decreased, ΔΨm increased, Cd-induced BRL-3A cell damage was alleviated, and cell apoptosis was inhibited. After the combined action of QE and Cd, Nrf2 and NQO1 mRNA and protein expression increased, Keap1 mRNA and protein expression decreased. Therefore, QE exerted an antioxidant effect by activating the Nrf2-Keap1 pathway in BRL-3A cells.

2,327 views
17 citations

Cadmium (Cd) is a hazardous environmental pollutant that menaces human and animal health and induces serious adverse effects in various organs, particularly the liver and kidneys. Thus, the current study was designed to look into the possible mechanisms behind the ameliorative activities of Tamarindus indica (TM) and coenzyme Q10 (CoQ) combined therapy toward Cd-inflicted tissue injury. Male Wistar rats were categorized into seven groups: Control (received saline only); TM (50 mg/kg); CoQ (40 mg/kg); Cd (2 mg/kg); (Cd + TM); (Cd + CoQ); and (Cd + TM + CoQ). All the treatments were employed once daily via oral gavage for 28 consecutive days. The results revealed that Cd exposure considerably induced liver and kidney damage, evidenced by enhancement of liver and kidney function tests. In addition, Cd intoxication could provoke oxidative stress evidenced by markedly decreased glutathione (GSH) content and catalase (CAT) activity alongside a substantial increase in malondialdehyde (MDA) concentrations in the hepatic and renal tissues. Besides, disrupted protein and lipid metabolism were noticed. Unambiguously, TM or CoQ supplementation alleviated Cd-induced hepatorenal damage, which is most likely attributed to their antioxidant and anti-inflammatory contents. Interestingly, when TM and CoQ were given in combination, a better restoration of Cd-induced liver and kidney damage was noticed than was during their individual treatments.

2,327 views
10 citations
Original Research
24 June 2022
Immunomodulatory Effect of Ginsenoside Rb2 Against Cyclophosphamide-Induced Immunosuppression in Mice
Siwen Zheng
5 more and 
Yingping Wang
Effect of ginsenoside Rb2 on ConA- and LPS- induced splenocyte proliferation, on NK cells activity, carbon clearance capacityin and the cytokines in CTX induced immunosuppressive mice. (A), ConA-induced splenocyte proliferation; (B), LPS-induced splenocyte proliferation; (C), NK cells activity; (D,E), carbon clearance capacityin; (F), IFN-γ; (G), TNF-α; (H), IgG; (I), IL-2. The data was expressed as mean ± S. D (n = 20). ##p < 0.01, compared to Normal. *p < 0.05; **p < 0.01, compared to Model.

Ginsenoside Rb2 (Rb2), a fundamental saponin produced and isolated from ginseng (Panax ginseng C.A. Meyer), has a wide range of biological actions. The objective of this investigation was to see if ginsenoside Rb2 has any immunomodulatory properties against cyclophosphamide (CTX)-induced immunosuppression. For the positive control group, levamisole hydrochloride (LD) was used. We discovered that intraperitoneal injection of Rb2 (5, 10, 20 mg/kg) could relieve CTX-induced immunosuppression by enhanced immune organ index, reduced the pathological characteristics of immunosuppression, promoted natural killer (NK) cells viability, improved cell-mediated immune response, boosted the IFN-γ (Interferon-gamma), TNF-α (Tumor necrosis factor-alpha), IL-2 (Interleukin-2), and IgG (Immunoglobulin G), as well as macrophage activity like carbon clearance and phagocytic index. Rb2 significantly elevated the mRNA expression of IL-4 (Interleukin-4), SYK (Tyrosine-protein kinase-SYK), IL-2, TNF-α, and IL-6 (Interleukin-6) in the spleen of CTX-injected animals. Molecular docking results showed that Rb2 had excellent binding properties with IL-4, SYK, IL-2, TNF, and IL-6, indicating the target protein might be strongly correlated with the immunomodulatory effect of Rb2. Taken together, ginsenoside Rb2 can improve the immune function that is declined in CTX-induced immunosuppressed mice, the efficacy maybe due to the regulation of related cytokine and mRNA expression.

3,496 views
19 citations
Open for submission
Frontiers Logo

Frontiers in Pharmacology

Shaping the Future of Predictive Toxicology: Addressing Challenges and New Approach Methodologies
Edited by Gladys Ouedraogo, Elisabet Berggren, Thomas Hartung
Deadline
27 December 2024
Submit a paper
Recommended Research Topics
Frontiers Logo

Frontiers in Pharmacology

Application of Computational Tools to Health and Environmental Sciences, Volume II
Edited by Patricia Ruiz, George D Loizou
44.7K
views
26
authors
7
articles
Frontiers Logo

Frontiers in Pharmacology

Toxicity Mechanisms, Exposure, Toxicokinetic and Risk Assessment Aspects of Metals, Toxic for Animals and Humans, Volume I
Edited by Yanzhu Zhu, Fatma Mohamady El-Demerdash, Xinwei Li, Michel Mansur Machado, Alex Boye
481K
views
150
authors
21
articles
Frontiers Logo

Frontiers in Pharmacology

Application of Computational Tools to Health and Environmental Sciences, Volume II
Edited by Patricia Ruiz, George D Loizou
27.7K
views
55
authors
8
articles
Frontiers Logo

Frontiers in Pharmacology

Advances in and Applications of Predictive Toxicology: 2022
Edited by Abdulkarim Najjar, Nynke Kramer, Iain Gardner, Thomas Hartung, Thomas Steger-Hartmann
22.9K
views
46
authors
7
articles
Frontiers Logo

Frontiers in Pharmacology

Toxicity Mechanisms, Exposure, Toxicokinetic and Risk Assessment Aspects of Metals, Toxic for Animals and Humans, Volume III
Edited by Michel Mansur Machado, Fatma Mohamady El-Demerdash, Alex Boye, Yanzhu Zhu, Xudong Sun, Xu Yang
Deadline
03 Jan 2025
Submit