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Abstract：
BACKGROUND: Medications, including chemotherapeutic drugs, contribute to male infertility as external factors by inducing oxidative stress in testicular cells. Shilajit is a naturally occurring bioactive antioxidant used in Ayurvedic medicine to treat a variety of ailments.
OBJECTIVE: This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics.
METHODS: Male Parkes mice received single intraperitoneal CPA injection (200 mg/kg BW) on day one, followed by daily supplementation of Shilajit (100 and 200 mg/kg BW) for one spermatogenic cycle.
RESULTS: CPA adversely affected testicular germ cell dynamics by inhibiting the conversion of spermatogonia-to-spermatids, altering testicular histoarchitecture, impairing Sertoli cell function and testicular steroidogenesis, and disturbing the testicular oxido-apoptotic balance. Shilajit supplementation restores testicular germ cell dynamics in CPA-exposed mice, as evidenced by improved histoarchitecture of the testis. Shilajit improves testicular daily production and sperm quality by promoting the conversion of spermatogonia (2C) into spermatids (1C), stimulating germ cell proliferation (PCNA), improving Sertoli cell function (N-Cadherin and β-Catenin), and maintaining the Bax/Bcl2 ratio. Additionally, Shilajit enhances testosterone biosynthesis by activating enzymes like 3β-HSD, and 17β-HSD. Shilajit also reduces testicular oxidative stress by increasing antioxidant enzyme activity (SOD) and decreasing lipid peroxidation (LPO). These effects are mediated by upregulation of the antioxidant protein Nrf-2 and downregulation of Keap-1.
CONCLUSIONS: The findings underscore the potent androgenic and antioxidant characteristics of Shilajit, as well as its ability to enhance fertility in cases of testicular damage caused by chemotherapeutic drugs.
OBJECTIVE: This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics.
METHODS: Male Parkes mice received single intraperitoneal CPA injection (200 mg/kg BW) on day one, followed by daily supplementation of Shilajit (100 and 200 mg/kg BW) for one spermatogenic cycle.
RESULTS: CPA adversely affected testicular germ cell dynamics by inhibiting the conversion of spermatogonia-to-spermatids, altering testicular histoarchitecture, impairing Sertoli cell function and testicular steroidogenesis, and disturbing the testicular oxido-apoptotic balance. Shilajit supplementation restores testicular germ cell dynamics in CPA-exposed mice, as evidenced by improved histoarchitecture of the testis. Shilajit improves testicular daily production and sperm quality by promoting the conversion of spermatogonia (2C) into spermatids (1C), stimulating germ cell proliferation (PCNA), improving Sertoli cell function (N-Cadherin and β-Catenin), and maintaining the Bax/Bcl2 ratio. Additionally, Shilajit enhances testosterone biosynthesis by activating enzymes like 3β-HSD, and 17β-HSD. Shilajit also reduces testicular oxidative stress by increasing antioxidant enzyme activity (SOD) and decreasing lipid peroxidation (LPO). These effects are mediated by upregulation of the antioxidant protein Nrf-2 and downregulation of Keap-1.
CONCLUSIONS: The findings underscore the potent androgenic and antioxidant characteristics of Shilajit, as well as its ability to enhance fertility in cases of testicular damage caused by chemotherapeutic drugs.
摘要：
背景：药物，包括化疗药物,通过诱导睾丸细胞的氧化应激作为外部因素导致男性不育。Shilajit是一种天然存在的生物活性抗氧化剂，用于阿育吠陀医学治疗各种疾病。
目的：本研究探讨了Shilajit抵消化疗药物环磷酰胺（CPA）对睾丸生殖细胞动力学的负面影响的潜力。
方法：雄性Parkes小鼠在第一天接受单次腹腔注射CPA（200mg/kg体重），然后每天补充Shilajit（100和200mg/kgBW），用于一个生精周期。
结果：CPA通过抑制精原细胞向精子细胞的转化对睾丸生殖细胞动力学产生不利影响，改变睾丸组织结构，损害支持细胞功能和睾丸类固醇生成，扰乱睾丸的氧化-凋亡平衡.Shilajit补充剂可恢复CPA暴露小鼠的睾丸生殖细胞动力学，睾丸组织结构的改进证明了这一点。Shilajit通过促进精原细胞（2C）转化为精子细胞（1C）来改善睾丸的日常生产和精子质量，刺激生殖细胞增殖（PCNA），改善支持细胞功能（N-钙粘蛋白和β-连环蛋白），并保持Bax/Bcl2比率。此外,Shilajit通过激活3β-HSD等酶来增强睾酮的生物合成，和17β-HSD。Shilajit还通过增加抗氧化酶活性（SOD）和减少脂质过氧化（LPO）来减少睾丸氧化应激。这些作用由抗氧化蛋白Nrf-2的上调和Keap-1的下调介导。
结论：研究结果强调了Shilajit的强效雄激素和抗氧化特性，以及在化疗药物引起的睾丸损伤情况下增强生育能力的能力。
目的：本研究探讨了Shilajit抵消化疗药物环磷酰胺（CPA）对睾丸生殖细胞动力学的负面影响的潜力。
方法：雄性Parkes小鼠在第一天接受单次腹腔注射CPA（200mg/kg体重），然后每天补充Shilajit（100和200mg/kgBW），用于一个生精周期。
结果：CPA通过抑制精原细胞向精子细胞的转化对睾丸生殖细胞动力学产生不利影响，改变睾丸组织结构，损害支持细胞功能和睾丸类固醇生成，扰乱睾丸的氧化-凋亡平衡.Shilajit补充剂可恢复CPA暴露小鼠的睾丸生殖细胞动力学，睾丸组织结构的改进证明了这一点。Shilajit通过促进精原细胞（2C）转化为精子细胞（1C）来改善睾丸的日常生产和精子质量，刺激生殖细胞增殖（PCNA），改善支持细胞功能（N-钙粘蛋白和β-连环蛋白），并保持Bax/Bcl2比率。此外,Shilajit通过激活3β-HSD等酶来增强睾酮的生物合成，和17β-HSD。Shilajit还通过增加抗氧化酶活性（SOD）和减少脂质过氧化（LPO）来减少睾丸氧化应激。这些作用由抗氧化蛋白Nrf-2的上调和Keap-1的下调介导。
结论：研究结果强调了Shilajit的强效雄激素和抗氧化特性，以及在化疗药物引起的睾丸损伤情况下增强生育能力的能力。
