title: Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress.
abstract: Cisplatin (CIS) is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg) administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell, hematocrit, hemoglobin, and endoplasmic reticulum stress protein levels all increased. Though CIS effectively treats cancer, at an increased dose it is toxic and life-threatening to the genitourinary system and other parts of the body.
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Soni
authors.affiliation: College of Pharmacy, Kyungsung University, Busan.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Choi
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Keshab Kumar
authors.initials: KK
authors.lastname: Karna
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: You
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Jai Seong
authors.initials: JS
authors.lastname: Cha
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Yu Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Hanyang University, Ansan, Republic of Korea.
authors.forename: Chul Young
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department 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 Hospital, Jeonju.
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood / Q000378:metabolism*; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002945:Cisplatin
keywords: CatSper; StAR protein; cisplatin; endoplasmic reticulum stress; oxidative stress; testicular toxicity