Arti Rajpoot, Kiran Yadav, Anupam Yadav, Raghav Kumar Mishra
{"title":"夏拉吉减轻化疗药物引起的睾丸毒性：睾丸生殖细胞动力学、类固醇生成调节和Nrf-2/Keap-1信号传导研究","authors":"Arti Rajpoot, Kiran Yadav, Anupam Yadav, Raghav Kumar Mishra","doi":"10.1016/j.jaim.2024.100930","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Objective</h3><p>This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics.</p></div><div><h3>Material and methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 (<em>N</em>-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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":15150,"journal":{"name":"Journal of Ayurveda and Integrative Medicine","volume":"15 4","pages":"Article 100930"},"PeriodicalIF":1.7000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0975947624000457/pdfft?md5=af3608f199f4c559dca7e0e6ea4faece&pid=1-s2.0-S0975947624000457-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Shilajit mitigates chemotherapeutic drug-induced testicular toxicity: Study on testicular germ cell dynamics, steroidogenesis modulation, and Nrf-2/Keap-1 signaling\",\"authors\":\"Arti Rajpoot, Kiran Yadav, Anupam Yadav, Raghav Kumar Mishra\",\"doi\":\"10.1016/j.jaim.2024.100930\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Objective</h3><p>This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics.</p></div><div><h3>Material and methods</h3><p>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.</p></div><div><h3>Results</h3><p>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 (<em>N</em>-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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":15150,\"journal\":{\"name\":\"Journal of Ayurveda and Integrative Medicine\",\"volume\":\"15 4\",\"pages\":\"Article 100930\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0975947624000457/pdfft?md5=af3608f199f4c559dca7e0e6ea4faece&pid=1-s2.0-S0975947624000457-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Ayurveda and Integrative Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0975947624000457\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ayurveda and Integrative Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0975947624000457","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
Shilajit mitigates chemotherapeutic drug-induced testicular toxicity: Study on testicular germ cell dynamics, steroidogenesis modulation, and Nrf-2/Keap-1 signaling
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.
Material and 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.
Conclusion
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
