Febuxostat attenuates testosterone-induced benign prostatic hyperplasia in rats via inhibiting JAK/STAT axis

作者: Amira M. Abo-Youssef , Hassan Afify , Amany A. Azouz , Hanaa M. Abdel-Rahman , Ashraf B. Abdel-Naim

DOI: 10.1016/J.LFS.2020.118414

关键词: ChemistryMalondialdehydeEndocrinologyInternal medicineJAK-STAT signaling pathwayFebuxostatXanthine oxidaseHyperplasiaSTAT proteinOxidative stressUric acid

摘要: Abstract Aim To investigate the possible modulatory effect of febuxostat in testosterone-induced benign prostatic hyperplasia (BPH) rats with emphasis on xanthine oxidase (XO)/Janus Kinases (JAK)/signal transducer and activator transcription (STAT) axis. Main methods Male Wistar were treated testosterone with/out febuxostat. Effect BPH was assessed at structural level by histopathology determination prostate weight/index. Cyclin D1 protein expression immunohistochemically ratio Bax/Bcl-2 mRNA determined real time polymerase chain reaction analysis (RT-PCR). Besides, uric acid serum colorimetrically. Prostatic XO activity, as well oxidative stress inflammatory markers evaluated. Additionally, western blot performed for JAK-1 phosphorylated form STAT-3 tissues. Key findings Results revealed that inhibited increase weight index compared to testosterone-treated group. ameliorated histopathological changes, prevented rise cyclin enhanced Bax/Bcl2 ratio. Febuxostat suppressed induced- activity prostates acid. Moreover, it regulated including; malondialdehyde (MDA), superoxide dismutase (SOD) glutathione (GSH) content. Also, contents interleukin-6 (IL-6), interleukin-1β (IL-1 β), tumor necrosis factor (TNF-α) nuclear (NF-κB). Interestingly, markedly reduced subsequent phosphorylation expression. Significance ameliorates via suppressing XO/JAK/STAT This may help re-purpose use inhibitors.

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