Diacerein ameliorates kidney injury induced by cisplatin in rats by activation of Nrf2/Ho-1 pathway and Bax down-regulation

Barakat, Nashwa; Barakat, Lamiaa; Zakaria, Mahmoud M.; Khirallah, Salma M.

doi:10.1016/j.sjbs.2021.08.025

Cited by 20 publications

(9 citation statements)

References 29 publications

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“…The present work demonstrated that acute dose of APAP caused a marked increase in the activity of caspase-3 as well as the expression of Bax with diminished expression of Bcl-2 [ 42 ], that DIA therapy restored these results in a dose-related manner. The anti-apoptotic effect of DIA has been reported previously in different tissues [ 12 , 22 , 23 , 30 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 72%

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

2022

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Background Acetaminophen (APAP) is a worldwide antipyretic as well as an analgesic medication. It has been extensively utilized during the outbreak of coronavirus 2019 (COVID-19). APAP misuse would lead to liver injury. Diacerein (DIA), an anthraquinone derivative, has antioxidant and inflammatory properties. Hence, this study attempted to evaluate the impact of DIA treatment on liver injury induced by APAP and its influence on nuclear factor-κB (NF-κB) /toll-like receptor 4 (TLR4)/high mobility group box-1(HMGB-1) signaling as well as the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression. Methods Male albino rats received 25 as well as 50 mg/kg/day DIA orally for seven days. One hour after the last administration, rats received APAP (1gm/kg, orally). For histopathological analysis, liver tissues and blood were collected, immunohistochemical (IHC) assay, biochemical assay, as well as quantitative real-time polymerase chain reaction (qRT-PCR). Results DIA markedly reduced liver injury markers and ameliorated histopathological changes. Moreover, DIA dose-dependently alleviated oxidative stress status caused by APAP administration along with inflammatory markers, including the level of interleukin-1 beta (IL-1β), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Furthermore, DIA downregulated protein levels as well as mRNA of HMGB-1, TLR4, NF-κB p65 expression, and enhanced PPAR-γ expression. Moreover, DIA ameliorated apoptotic (Bax) and caspase-3 expressions and increased the anti-apoptotic (Bcl2) expression. Conclusions This study demonstrated that DIA exerts anti-apoptotic, anti-inflammatory, and antioxidant properties against liver injury induced by APAP that is attributed to inhibition of the HMGB1/TLR4/NF-κB pathway, besides upregulation of the expression of PPAR-γ.

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Section: Discussionmentioning

confidence: 72%

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

2022

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“…This indicates the beneficial effect of DIA in reducing the fibrosis which agrees with Barakat and his colleges. 69…”

Section: Discussionmentioning

confidence: 99%

TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats

Abdel-Aziz,

Fathy,

Hafez

et al. 2023

Hum Exp Toxicol

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Purpose Pulmonary fibrosis (PF) is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on PF injury has not yet been fully clarified. Therefore, the current study aimed to detect its protective effect on lung tissue with the explanation of possible underlying mechanisms. Methods Adult male albino rats were assigned to four groups: control group, diacerein control group, PF non-treated group, and PF diacerein pretreated group. Lung tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and myeloid differentiation factor 88 (MyD88) levels were determined. Histopathological examination of lung tissue and immunohistochemical studies of nuclear factor-kappa B (NF-κB), and transforming growth factor- β (TGF-β) were also done. Results Diacerein pretreatment has the ability to restore the PF damaging effect, proved by the reduction of the oxidative stress and lung tissue inflammation via downregulation of TLR4/NF-κB signaling pathway together with the restoration of TGF-β level and improvement of the histopathological and immunohistochemical study findings in the lung tissue. Conclusion These results suggested the protective effect of diacerein on PF relies on its antioxidant and anti-inflammatory effects reducing TLR4/NF-κB signaling pathway.

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“…In investigations carried out in vitro and in vivo on animals and humans, Rhein, the active metabolic form of Diacerhein, has been demonstrated to decrease the manufacture and activity of proin ammatory cytokines, particularly IL-1β [29,47] . In addition, the substance directly affects in ammatory cells by preventing human neutrophils from producing superoxide anion, lysosomal enzyme release, chemotaxis, and phagocytic activity.…”

Section: Discussionmentioning

confidence: 99%

Diacerhein Attenuates Sepsis-induced Pulmonary Vascular Endothelial barrier Dysfunction via Inhibition of Advanced Glycation End Products

Wei

Sun

et al. 2023

Preprint

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AIM Acute lung injury in sepsis is a life-threatening clinical problem with high mortality and few treatment options, posing a significant challenge for clinicians. Powerful anti-inflammatory anthraquinone derivative dialcerhein (DIA) has numerous targets. The objective of this investigation is to ascertain whether DIA and potential molecular targets can protect mice against sepsis-induced deteriorate of the pulmonary vascular endothelial barrier. METHODS Cecal ligation and puncture (CLP) was used to induce sepsis in mice, followed by DIA administration. Survival rate, serum biochemical indicators and advanced glycation end products (AGEs), pulmonary vascular endothelial barrier function, glucose tolerance, and protein expression in lung tissue were all studied using molecular and biochemical approaches. RESULTS In septic mice lung tissue, DIA therapy normalized CLP-induced survival rate, vascular hyperpermeability, pulmonary vascular endothelial barrier dysfunction, inflammatory response, insulin tolerance test, AGEs level, and VE-cadherin phosphorylation level. Furthermore, AGEs and Scr interventions could greatly impair the therapeutic efficacy of DIA. CONCLUSION In this study, DIA alleviated pulmonary vascular endothelial barrier dysfunction in septic mice by regulating inflammation and lowering insulin resistance through AGEs inhibition. These findings showed that DIA could be a potential therapeutic for sepsis patients.

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Diacerein ameliorates kidney injury induced by cisplatin in rats by activation of Nrf2/Ho-1 pathway and Bax down-regulation

Cited by 20 publications

References 29 publications

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats

Diacerhein Attenuates Sepsis-induced Pulmonary Vascular Endothelial barrier Dysfunction via Inhibition of Advanced Glycation End Products

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