Acacia saligna extract alleviates quetiapine-induced sexual toxicity in male albino rats: Insights from UPLC-MS/MS metabolite profiling, structural and PI3K/NF-κB pathway assessments

金合欢提取物可减轻雄性白化大鼠中喹硫平引起的性毒性:从 UPLC-MS/MS 代谢物分析、结构和 PI3K/NF-κB 通路评估中获得的见解

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作者:Shimaa Mohammad Yousof, Shaimaa A Shehata, Ezzat A Ismail, Samar M Abd El-Moneam, Basma S A Mansour, Mohamed A Farag, Abdelsamed I Elshamy, Abd El-Nasser G El Gendy, Ahmed Serag, Noha M Abd El-Fadeal, Rehab Ibrahim Abdel-Karim, Mostafa M Mostafa, Dina H El-Sheikh, Mohamed A Zayed

Aim

To investigate the protective role of A. saligna flower extract against QET-induced sexual toxicity, and to elucidate the possible underlying mechanisms through metabolomic and physiological studies.

Background

Quetiapine (QET) abuse has increased due to its anxiolytic and hedonic effects, necessitating protective adjunct treatments. Acacia saligna (A. saligna) flowers, used in traditional medicine, have potential health benefits.

Conclusion

The extract from A. saligna, which contains a high concentration of antioxidants and anti-inflammatory chemicals, effectively mitigates sexual toxicity caused by QET. This study provided the first known explanation of the hypothesized processes behind the protective properties of A. saligna through biological, biochemical, and histological parameters. The results emphasize the potential of A. saligna as a safeguarding agent against drug-induced sexual toxicity.

Methods

A. saligna extract was subjected to metabolite profiling via High-Resolution Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI-qTOF-MS). Forty-eight adult male albino rats were assigned into six groups for 30 days. The intracavernosal pressure (ICP), semen, biochemical, hormonal, histological, genetic and Western blot (WB) analyses were determined.

Results

A. saligna extract is rich in phenolic compounds, flavonoids, tannins, and unsaturated fatty acids. QET significantly decreased ICP and negatively affected semen parameters. A. saligna mitigated decreased sperm motility and ameliorated overexpressed proinflammatory genes in QET-55 group. A. saligna ameliorated the reduction of the antioxidant biomarkers, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), concurrent with downregulation of the nuclear factor kappa B (NF-κB) protein. A. saligna counteracted the disrupted testicular and prostatic structures revealed by histological examination.

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