The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis
Cisplatin (CP) is a productive anti-tumor used to treat numerous tumors. However, multiple toxicities discourage prolonged use, especially toxicity on the reproductive system. This experiment was mapped out to determine the potential therapeutic impact of Bilobetin on CP-induced testicular damage. H...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1134 |
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| author | Walaa A. Negm Aya H. El-Kadem Ismail A. Hussein Moneerah J. Alqahtani |
| author_facet | Walaa A. Negm Aya H. El-Kadem Ismail A. Hussein Moneerah J. Alqahtani |
| author_sort | Walaa A. Negm |
| collection | DOAJ |
| description | Cisplatin (CP) is a productive anti-tumor used to treat numerous tumors. However, multiple toxicities discourage prolonged use, especially toxicity on the reproductive system. This experiment was mapped out to determine the potential therapeutic impact of Bilobetin on CP-induced testicular damage. Herein, Bilobetin was isolated from <i>Cycas thouarsii</i> leaves R. Br ethyl acetate fractions for the first time. A single dose of CP (7 mg/kg, IP) was used to evoke testicular toxicity on the third day. Rats were classified into five groups; Normal control, Bilobetin 12 mg/kg, Untreated CP, and CP treated with Bilobetin (6 and 12 mg/kg, respectively) orally daily for ten days. Bilobetin treatment ameliorated testicular injury. In addition, it boosted serum testosterone levels considerably and restored relative testicular weight. Nevertheless, apoptosis biomarkers such as P53, Cytochrome-C, and caspase-3 decreased significantly. Additionally, it enhanced the testes’ antioxidant status via the activation of Nrf-2, inhibition of Keap-1, and significant elevation of SOD activity in addition to a reduction in lipid peroxidation. Histopathologically, Bilobetin preserved testicular architecture and improved testicular immunostaining of Ki67 substantially, showing evidence of testicular regeneration. Bilobetin’s beneficial effects on CP-induced testicular damage are associated with enhanced antioxidant effects, lowered apoptotic signals, and the restoration of testes’ regenerative capability. In addition, Bilobetin may be used in combination with CP in treatment protocols to mitigate CP-induced testicular injury. |
| first_indexed | 2024-03-10T03:17:02Z |
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| language | English |
| last_indexed | 2024-03-10T03:17:02Z |
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| series | Biomedicines |
| spelling | doaj.art-f46040473ca948b286aaaa06fcbafb672023-11-23T10:11:32ZengMDPI AGBiomedicines2227-90592022-05-01105113410.3390/biomedicines10051134The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and ApoptosisWalaa A. Negm0Aya H. El-Kadem1Ismail A. Hussein2Moneerah J. Alqahtani3Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptDepartment of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptDepartment of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaCisplatin (CP) is a productive anti-tumor used to treat numerous tumors. However, multiple toxicities discourage prolonged use, especially toxicity on the reproductive system. This experiment was mapped out to determine the potential therapeutic impact of Bilobetin on CP-induced testicular damage. Herein, Bilobetin was isolated from <i>Cycas thouarsii</i> leaves R. Br ethyl acetate fractions for the first time. A single dose of CP (7 mg/kg, IP) was used to evoke testicular toxicity on the third day. Rats were classified into five groups; Normal control, Bilobetin 12 mg/kg, Untreated CP, and CP treated with Bilobetin (6 and 12 mg/kg, respectively) orally daily for ten days. Bilobetin treatment ameliorated testicular injury. In addition, it boosted serum testosterone levels considerably and restored relative testicular weight. Nevertheless, apoptosis biomarkers such as P53, Cytochrome-C, and caspase-3 decreased significantly. Additionally, it enhanced the testes’ antioxidant status via the activation of Nrf-2, inhibition of Keap-1, and significant elevation of SOD activity in addition to a reduction in lipid peroxidation. Histopathologically, Bilobetin preserved testicular architecture and improved testicular immunostaining of Ki67 substantially, showing evidence of testicular regeneration. Bilobetin’s beneficial effects on CP-induced testicular damage are associated with enhanced antioxidant effects, lowered apoptotic signals, and the restoration of testes’ regenerative capability. In addition, Bilobetin may be used in combination with CP in treatment protocols to mitigate CP-induced testicular injury.https://www.mdpi.com/2227-9059/10/5/1134bilobetin<i>Cycas thouarsii</i>caspase-3cisplatinkeap-1Ki67 |
| spellingShingle | Walaa A. Negm Aya H. El-Kadem Ismail A. Hussein Moneerah J. Alqahtani The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis Biomedicines bilobetin <i>Cycas thouarsii</i> caspase-3 cisplatin keap-1 Ki67 |
| title | The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis |
| title_full | The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis |
| title_fullStr | The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis |
| title_full_unstemmed | The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis |
| title_short | The Mechanistic Perspective of Bilobetin Protective Effects against Cisplatin-Induced Testicular Toxicity: Role of Nrf-2/Keap-1 Signaling, Inflammation, and Apoptosis |
| title_sort | mechanistic perspective of bilobetin protective effects against cisplatin induced testicular toxicity role of nrf 2 keap 1 signaling inflammation and apoptosis |
| topic | bilobetin <i>Cycas thouarsii</i> caspase-3 cisplatin keap-1 Ki67 |
| url | https://www.mdpi.com/2227-9059/10/5/1134 |
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