Pharmacological study of the role of uric acid lowering agents on testosterone-induced benign prostatic hypertrophy via akt/ mtor signaling pathway /
Nibrass Taher Hussein Abdali,
Pharmacological study of the role of uric acid lowering agents on testosterone-induced benign prostatic hypertrophy via akt/ mtor signaling pathway / دراسة دوائية لدور عامل خفض حمض اليوريك على تضخم البروستات الحميد المحدث بالتستوستيرون من خلال مسار أكت/إم تور by Nibrass Taher Hussein Abdali ; Supervision Prof. Dr. Hala Fahmy Zaki, Prof. Dr. Laila Ahmed Abdelaziz, Dr. Yasmin Shokr Mohamed, Dr. Hassan Afify Hassan. - 119 pages : illustrations ; 25 cm. + CD.
Thesis (Ph.D)-Cairo University, 2025.
Bibliography: pages 96-119.
Benign prostatic hyperplasia is the most common urological condition among elderly men. Because of modifiable metabolic risk factors, the prevalence of benign prostatic hyperplasia is rising. Emerging evidence links elevated uric acid levels to prostatic inflammation and hyperplasia, potentially through oxidative stress and activation of proliferative pathways. Tart-cherry and eugenol were not previously investigated against benign prostatic hyperplasia (BPH).
Eighty healthy male Wistar rats were utilized in the current study and subdivided randomly into ten groups (n=8). BPH was induced by administering testosterone (3 mg/kg; s.c.) for 2 weeks. This was done either alone or after one-week pretreatment with probenecid (200 mg/kg/day; i.p), tart-cherry (500 mg/kg/day; p.o.), eugenol (10 mg/kg/day; p.o.), or a combination of these agents. At the end of the experiment, the prostate tissue was used for biochemical analysis, reverse transcriptase polymerase chain reaction, Western blot analysis, and histological and immunohistochemical assessment
The results revealed a significant increase in prostate index, along with upregulation of cell survival markers like cyclin D1 and characteristic histopathological changes indicative of BPH post-testosterone administration. Additionally, testosterone induced elevated uric acid levels, oxidative stress, inflammatory markers, and activation of pro-survival pathways including PI3-K/AKt/mTOR and NFκB. However, intervention with probenecid, tart-cherry, eugenol adminsterd individually or in combination effectively mitigated these changes, showcasing their anti-inflammatory, antioxidative, and anti-hyperproliferative properties. Notably, the combination therapy demonstrated superior efficacy compared to individual treatments. خلصت الدراسة إلى أن إعطاء البروبنيسيد والكرزالمرّ والإيوجينول، سواء بشكل منفرد أو مجتمع، قد أظهر تأثيرًا وقائيًا ضد فرط تنسج البروستات الحميد المحفز بالتستوستيرون في الفئران، مما يوفر نهجًا متعدد الأهداف يشمل مكافحة الالتهاب، تقليل الإجهاد التأكسدي، وكبح مسارات تكاثر الخلايا.
Text in English and abstract in Arabic & English.
Toxicology
علم السموم
benign prostatic hyperplasia tart cherry eugenol inflammation probenecid testosterone تضخم البروستات الحميد الكرز الحامض
615.9
Pharmacological study of the role of uric acid lowering agents on testosterone-induced benign prostatic hypertrophy via akt/ mtor signaling pathway / دراسة دوائية لدور عامل خفض حمض اليوريك على تضخم البروستات الحميد المحدث بالتستوستيرون من خلال مسار أكت/إم تور by Nibrass Taher Hussein Abdali ; Supervision Prof. Dr. Hala Fahmy Zaki, Prof. Dr. Laila Ahmed Abdelaziz, Dr. Yasmin Shokr Mohamed, Dr. Hassan Afify Hassan. - 119 pages : illustrations ; 25 cm. + CD.
Thesis (Ph.D)-Cairo University, 2025.
Bibliography: pages 96-119.
Benign prostatic hyperplasia is the most common urological condition among elderly men. Because of modifiable metabolic risk factors, the prevalence of benign prostatic hyperplasia is rising. Emerging evidence links elevated uric acid levels to prostatic inflammation and hyperplasia, potentially through oxidative stress and activation of proliferative pathways. Tart-cherry and eugenol were not previously investigated against benign prostatic hyperplasia (BPH).
Eighty healthy male Wistar rats were utilized in the current study and subdivided randomly into ten groups (n=8). BPH was induced by administering testosterone (3 mg/kg; s.c.) for 2 weeks. This was done either alone or after one-week pretreatment with probenecid (200 mg/kg/day; i.p), tart-cherry (500 mg/kg/day; p.o.), eugenol (10 mg/kg/day; p.o.), or a combination of these agents. At the end of the experiment, the prostate tissue was used for biochemical analysis, reverse transcriptase polymerase chain reaction, Western blot analysis, and histological and immunohistochemical assessment
The results revealed a significant increase in prostate index, along with upregulation of cell survival markers like cyclin D1 and characteristic histopathological changes indicative of BPH post-testosterone administration. Additionally, testosterone induced elevated uric acid levels, oxidative stress, inflammatory markers, and activation of pro-survival pathways including PI3-K/AKt/mTOR and NFκB. However, intervention with probenecid, tart-cherry, eugenol adminsterd individually or in combination effectively mitigated these changes, showcasing their anti-inflammatory, antioxidative, and anti-hyperproliferative properties. Notably, the combination therapy demonstrated superior efficacy compared to individual treatments. خلصت الدراسة إلى أن إعطاء البروبنيسيد والكرزالمرّ والإيوجينول، سواء بشكل منفرد أو مجتمع، قد أظهر تأثيرًا وقائيًا ضد فرط تنسج البروستات الحميد المحفز بالتستوستيرون في الفئران، مما يوفر نهجًا متعدد الأهداف يشمل مكافحة الالتهاب، تقليل الإجهاد التأكسدي، وكبح مسارات تكاثر الخلايا.
Text in English and abstract in Arabic & English.
Toxicology
علم السموم
benign prostatic hyperplasia tart cherry eugenol inflammation probenecid testosterone تضخم البروستات الحميد الكرز الحامض
615.9