Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats
Abstract Background DA-9401 was prepared as a mixture of Chinese medicinal herb extracts from roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae). The present study was designed to investigate the possible pro...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-019-0805-2 |
| _version_ | 1819093825491042304 |
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| author | Keshab Kumar Karna Bo Ram Choi Jae Hyung You Yu Seob Shin Kiran Kumar Soni Wan Shou Cui Sung Won Lee Chul Young Kim Hye Kyung Kim Jong Kwan Park |
| author_facet | Keshab Kumar Karna Bo Ram Choi Jae Hyung You Yu Seob Shin Kiran Kumar Soni Wan Shou Cui Sung Won Lee Chul Young Kim Hye Kyung Kim Jong Kwan Park |
| author_sort | Keshab Kumar Karna |
| collection | DOAJ |
| description | Abstract Background DA-9401 was prepared as a mixture of Chinese medicinal herb extracts from roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae). The present study was designed to investigate the possible protective role of DA-9401 in adriamycin (ADR)-induced testicular toxicity associated with oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis. Methods Fifty healthy 8-week-old male Sprague–Dawley rats were equally divided into five groups. The first CTR group was treated with normal saline 2 ml/day by gavage. The second was treated with DA-100 (DA-9401 100 mg/kg/day). The third (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and DA-9401 was given to the fourth ADR + DA-100 (100 mg/kg/day p.o) group and fifth ADR + DA-200 (200 mg/kg/day p.o) group. At the end of the 8-week treatment period, body weight, reproductive organ weights, fertility rate, pups per female were recorded, and serum were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathological changes, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), oxidative stress markers and expression levels of endoplasmic reticulum (ER) stress markers, apoptosis markers, tight junction protein markers, steroidogenic acute regulatory protein (StAR), cation channel of sperm (CatSper) and glycogen synthase kinase-3 (GSK-3) by western blot. Results DA-9401 administration to ADR-treated rats significantly decreased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, interleukin-6, TNF-α, MDA level, ROS/RNS level, ER stress response protein levels, tunnel positive cells, cleaved caspase-3, and Bax/Bcl2 ratio. Moreover, pretreatment with DA-9401 significantly increased body weight, reproductive organ weights, fertility rate, pups per female, Johnsen’s score, spermatogenic cell density, sperm count and sperm motility, serum testosterone concentration, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), tight junction protein markers, star protein level, CatSper, and GSK-3 level. Conclusions ADR treatment can markedly impair testicular function and induce testicular cell death presumably by causing significant changes in oxidative stress, ER stress, and mitochondrial pathway. DA-9401 exerts beneficial effects against oxidative stress, ER stress, and mitochondria-mediated cell death pathway in testis tissue by up-regulating expression levels of tight junction protein markers, steroidogenic acute regulatory protein, GSK-3 alpha, and cation channels of sperm. |
| first_indexed | 2024-12-21T23:17:40Z |
| format | Article |
| id | doaj.art-ac8809183d91487f88e410dad89c841f |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-21T23:17:40Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-ac8809183d91487f88e410dad89c841f2022-12-21T18:46:53ZengBMCCancer Cell International1475-28672019-04-0119111110.1186/s12935-019-0805-2Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley ratsKeshab Kumar Karna0Bo Ram Choi1Jae Hyung You2Yu Seob Shin3Kiran Kumar Soni4Wan Shou Cui5Sung Won Lee6Chul Young Kim7Hye Kyung Kim8Jong Kwan Park9Department of Urology, Institute for Medical Sciences, Chonbuk National University Medical School–Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University HospitalDepartment of Urology, Institute for Medical Sciences, Chonbuk National University Medical School–Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University HospitalDepartment of Urology, Institute for Medical Sciences, Chonbuk National University Medical School–Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University HospitalDepartment of Urology, Institute for Medical Sciences, Chonbuk National University Medical School–Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University HospitalDepartment of Physiology & Biophysics, University of Mississippi Medical CenterAndrology Center, Peking University First HospitalDepartment of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of MedicineCollege of Pharmacy, Hanyang UniversityCollege of Pharmacy, Kyungsung UniversityDepartment of Urology, Institute for Medical Sciences, Chonbuk National University Medical School–Biomedical Research and Institute and Clinical Trial Center for Medical Devices, Chonbuk National University HospitalAbstract Background DA-9401 was prepared as a mixture of Chinese medicinal herb extracts from roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae). The present study was designed to investigate the possible protective role of DA-9401 in adriamycin (ADR)-induced testicular toxicity associated with oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis. Methods Fifty healthy 8-week-old male Sprague–Dawley rats were equally divided into five groups. The first CTR group was treated with normal saline 2 ml/day by gavage. The second was treated with DA-100 (DA-9401 100 mg/kg/day). The third (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and DA-9401 was given to the fourth ADR + DA-100 (100 mg/kg/day p.o) group and fifth ADR + DA-200 (200 mg/kg/day p.o) group. At the end of the 8-week treatment period, body weight, reproductive organ weights, fertility rate, pups per female were recorded, and serum were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathological changes, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), oxidative stress markers and expression levels of endoplasmic reticulum (ER) stress markers, apoptosis markers, tight junction protein markers, steroidogenic acute regulatory protein (StAR), cation channel of sperm (CatSper) and glycogen synthase kinase-3 (GSK-3) by western blot. Results DA-9401 administration to ADR-treated rats significantly decreased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, interleukin-6, TNF-α, MDA level, ROS/RNS level, ER stress response protein levels, tunnel positive cells, cleaved caspase-3, and Bax/Bcl2 ratio. Moreover, pretreatment with DA-9401 significantly increased body weight, reproductive organ weights, fertility rate, pups per female, Johnsen’s score, spermatogenic cell density, sperm count and sperm motility, serum testosterone concentration, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), tight junction protein markers, star protein level, CatSper, and GSK-3 level. Conclusions ADR treatment can markedly impair testicular function and induce testicular cell death presumably by causing significant changes in oxidative stress, ER stress, and mitochondrial pathway. DA-9401 exerts beneficial effects against oxidative stress, ER stress, and mitochondria-mediated cell death pathway in testis tissue by up-regulating expression levels of tight junction protein markers, steroidogenic acute regulatory protein, GSK-3 alpha, and cation channels of sperm.http://link.springer.com/article/10.1186/s12935-019-0805-2DA-9401Adriamycin (ADR)Endoplasmic reticulum (ER) stressOxidative stressApoptosisSteroidogenic acute regulatory protein (StAR) |
| spellingShingle | Keshab Kumar Karna Bo Ram Choi Jae Hyung You Yu Seob Shin Kiran Kumar Soni Wan Shou Cui Sung Won Lee Chul Young Kim Hye Kyung Kim Jong Kwan Park Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats Cancer Cell International DA-9401 Adriamycin (ADR) Endoplasmic reticulum (ER) stress Oxidative stress Apoptosis Steroidogenic acute regulatory protein (StAR) |
| title | Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats |
| title_full | Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats |
| title_fullStr | Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats |
| title_full_unstemmed | Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats |
| title_short | Cross-talk between ER stress and mitochondrial pathway mediated adriamycin-induced testicular toxicity and DA-9401 modulate adriamycin-induced apoptosis in Sprague–Dawley rats |
| title_sort | cross talk between er stress and mitochondrial pathway mediated adriamycin induced testicular toxicity and da 9401 modulate adriamycin induced apoptosis in sprague dawley rats |
| topic | DA-9401 Adriamycin (ADR) Endoplasmic reticulum (ER) stress Oxidative stress Apoptosis Steroidogenic acute regulatory protein (StAR) |
| url | http://link.springer.com/article/10.1186/s12935-019-0805-2 |
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