Diacerein Downregulates NLRP3/Caspase-1/IL-1β and IL-6/STAT3 Pathways of Inflammation and Apoptosis in a Rat Model of Cadmium Testicular Toxicity

Fouad, Amr A.; Abdel-Aziz, Asmaa Mohamed; Hamouda, Azza A H

doi:10.1007/s12011-019-01865-6

Cited by 72 publications

(45 citation statements)

References 27 publications

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“…The first clinical study for a NLRP3 inflammasome inhibitor (Tranilast) to treat COVID-19 is ongoing and registered in the Chinese clinical trial registry ( 45 ). Other studies are still in a pre-clinical phase and study the effect on acute lung injury or on cell lines for example with resveratrol ( 46 ), tetracycline ( 47 ) or erythropoietin ( 48 ) or nicardipine, a L-type calcium antagonist ( 49 ), lidocaine ( 50 ) CP-456,773 ( 51 ), Diacerein ( 52 ). For colchicine it is hypothesized that it has an effect on NLRP3-mediated diseases ( 53 ).…”

Section: Treatment Optionsmentioning

confidence: 99%

Severe COVID-19: NLRP3 Inflammasome Dysregulated

2020

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SARS-CoV-2 might directly activate NLRP3 inflammasome resulting in an endogenous adjuvant activity necessary to mount a proper adaptive immune response against the virus. Heterogeneous response of COVID-19 patients could be attributed to differences in not being able to properly downregulate NLRP3 inflammasome activation. This relates to the fitness of the immune system of the individual challenged by the virus. Patients with a reduced immune fitness can demonstrate a dysregulated NLRP3 inflammasome activity resulting in severe COVID-19 with tissue damage and a cytokine storm. We sketch the outlines of five possible scenarios for COVID-19 in medical practice and provide potential treatment options targeting dysregulated endogenous adjuvant activity in severe COVID-19 patients.

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Section: Treatment Optionsmentioning

confidence: 99%

Severe COVID-19: NLRP3 Inflammasome Dysregulated

2020

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“…In addition to directly inducing structural damage in the testis, oxidative stress is also capable of stimulating apoptosis both in vitro [ 17 ] and in vivo [ 12 , 18 ]. In fact, Cd has been shown to increase the expression of proapoptotic factors such B cell-lymphoma (Bcl)-2-associated X protein (Bax), of the key regulatory protein p53, and of caspase-3 as well as to reduce that of the antiapoptotic Bcl-2 [ 11 , 18 , 19 , 20 , 21 ]. It was also observed that germ cell apoptosis might be the consequence of a Cd-induced reduction in testosterone level [ 22 ] with detachment of immature germ cells from the seminiferous epithelium [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

et al. 2021

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It is known that cadmium damages testis structure and functionality. We examined the effects of nutraceuticals such as a flavonoid-rich extract of bergamot juice (BJe), alone or in association with curcumin (Cur) and resveratrol (Re), on mice testicular dysfunction caused by cadmium chloride (CdCl2). Controversial data on the protective effects of Cur and Re are available, while no evidence on the possible role of BJe exists. Adult male C57 BL/6J mice were administered with CdCl2 and treated with Cur, Re, or BJe alone or in combination for 14 days. Then, testes were removed and processed for molecular, structural, and immunohistochemical analyses. CdCl2 increased the mRNA of IL-1β, TNF-α, p53, and BAX while reduced that of Bcl-2 and induced tubular lesions and apoptosis of germinal cells. Cur, Re, and BJe at 40 mg/kg significantly improved all of these parameters and events, although BJe at 20 mg/kg showed a lower protective effect. The association of Cur, Re, and BJe at both doses of 50/20/20 and 100/20/40 mg/kg brought each parameter close to those of the control. Our results indicate that the nutraceuticals employed in this study and their associations exert a positive action against Cd-induced testicular injury, suggesting a possible protection of testis functionality in subjects exposed to environmental toxicants.

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“…12,22 As a crucial bio-signaling molecule, ROS tumor necrosis factor-α (TNF-α), and activated nuclear factor-κB (NF-κB) inflammatory responses. 28 Increasing evidence indicate that the toll-like receptors (TLRs) and SMAD family proteins play an important role in the inflammatory response. 29,30 We also observed that the that Cd induced apoptosis in human oligoglial cells, 31 spleen cells, 32 rat renal tubular epithelial cells 33 and Pacific red bream white cells.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggested that the antioxidant ability of HTR‐8/SVneo cells was increased through upregulating the expression of SOD1 and ROS1 when the cells were exposed in Cd. Meanwhile, it has been reported that Cd exposure induced NOD‐like receptor protein‐3 (NLRP3) inflammasome, with subsequent activation of caspase‐1, and increased production of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), interleukin‐18 (IL‐18), and tumor necrosis factor‐α (TNF‐α), and activated nuclear factor‐κB (NF‐κB) inflammatory responses 28 . Increasing evidence indicate that the toll‐like receptors (TLRs) and SMAD family proteins play an important role in the inflammatory response 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Cadmium cytotoxicity and possible mechanisms in human trophoblast HTR‐8/SVneo cells

Liao

Zheng

et al. 2021

Environmental Toxicology

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The accumulation of cadmium (Cd) in the human body through food chain can lead to adverse pregnancy outcomes. In this study, Cd cytotoxicity and its mechanisms in HTR-8/SVneo cells were investigated. Cd disrupted the cellular submicrostructure and inhibited the cell viability in a time-and dose-dependent manner. The levels of reactive oxygen species, malondialdehyde content, and the activities of glutathione peroxidase (GSH-Px) and total superoxode dismutase (T-SOD) were concentrationdependently increased by Cd. In addition, Cd dose-dependently inducedcell apoptosis and decreased cell migration and invasion capacities. Finally, Cd significantly upregulated all the genes related to oxidative stress (SOD1, ROS1, and HSPA6), inflammatory response, cell cycle, apoptosis, and migration and invasion. This study will provide insights into the prevention and treatment of pregnancy-related diseases caused by Cd intoxication.

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Diacerein Downregulates NLRP3/Caspase-1/IL-1β and IL-6/STAT3 Pathways of Inflammation and Apoptosis in a Rat Model of Cadmium Testicular Toxicity

Cited by 72 publications

References 27 publications

Severe COVID-19: NLRP3 Inflammasome Dysregulated

Severe COVID-19: NLRP3 Inflammasome Dysregulated

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

Cadmium cytotoxicity and possible mechanisms in human trophoblast HTR‐8/SVneo cells

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