Diacerein ameliorates testosterone-induced benign prostatic hyperplasia in rats: Effect on oxidative stress, inflammation and apoptosis

El‐Sherbiny, Mohamed; El-Shafey, Mohamed; El-Agawy, Mosaab Salah El-din; Mohamed, Abdelaty Shawky; Eisa, Nada H.; Elsherbiny, Nehal M.

doi:10.1016/j.intimp.2021.108082

Cited by 28 publications

(19 citation statements)

References 42 publications

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“…Several studies emphasized that excessive ROS causes mitochondrial damage, which eventually activates the caspase cascade, leading to apoptosis. Caspase-3 has been proven to contribute to the pathway of hepatocellular apoptosis [ 33 , 34 , 39 ]. In addition, the balance between pro-apoptotic as well as anti-apoptotic Bcl-2 protein BAX displayed a pivotal role in regulating apoptosis during APAP hepatotoxicity [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

2022

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“…It is well‐documented that BPH is associated with dihydrotestosterone (DHT). [ 51,58–60 ] TST tends to drop with age, whereas DHT levels inside the prostate stay within the normal range. [ 61 ] In most cases, the 5‐alpha‐reductase enzyme is responsible for transforming TST into DHT.…”

Section: Discussionmentioning

confidence: 99%

Probenecid ameliorates testosterone‐induced benign prostatic hyperplasia: Implications of PGE‐2 on ADAM‐17/EGFR/ERK1/2 signaling cascade

Abdel-Fattah

Fetoh

Afify

et al. 2023

J Biochem & Molecular Tox

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Benign prostatic hyperplasia (BPH) is one of the most prevalent clinical disorders in the elderly. Probenecid (Prob) is a well‐known FDA‐approved therapy for gout owing to its uricosuric effect. The present study evaluated the use of Prob for BPH as a COX‐2 inhibitor. Prob (100 and 200 mg/kg) was intraperitoneally injected into male Wistar rats daily for 3 weeks. In the second week, testosterone (3 mg/kg) was subcutaneously injected to induce BPH. Compared with BPH‐induced rats, Prob treatment reduced prostate weight and index and improved histopathological architecture. The protease activity of ADAM‐17/TACE and its ligands (TGF‐α and TNF‐α) were regulated by prob, which in turn abolished EGFR phosphorylation, and several inflammatory mediators (COX‐2, PGE2, NF‐κB (p65), and IL‐6) were suppressed. By reducing the nuclear import of extracellular regulated kinase protein 1/2 (ERK1/2), Prob helped re‐establish the usual equilibrium between antiapoptotic proteins like Bcl‐2 and cyclin D1 and proapoptotic proteins like Bax. All of these data point to Prob as a promising treatment for BPH because of its ability to inhibit COX‐2‐syntheiszed PGE2 and control the ADAM‐17/TGF‐α‐induced EGFR/ERK1/2 signaling cascade. These findings might help to repurpose Prob for the treatment of BPH.

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“…Research has suggested that erythrocyte SOD activity was significantly decreased in BPH patients as compared with age-and sex-matched healthy subjects [26]. Moreover, T injection in the BPH model has been shown to weaken cellular antioxidant mechanisms, including a decrease in SOD activity [27][28][29]. In this study, the SOD activity of prostates in the ASTtreated rats increased, while the SOD activity of prostates in the 40 mg/kg and 80 mg/kg AST-treated rats was significantly higher than that in the BPH model control rats.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats

et al. 2021

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This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.

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Diacerein ameliorates testosterone-induced benign prostatic hyperplasia in rats: Effect on oxidative stress, inflammation and apoptosis

Cited by 28 publications

References 42 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

Probenecid ameliorates testosterone‐induced benign prostatic hyperplasia: Implications of PGE‐2 on ADAM‐17/EGFR/ERK1/2 signaling cascade

Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats

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