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Drug Design, Development and Therapy Volume 10, 2016 - Issue
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Hypothesis

Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress

Kiran Kumar Soni1 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
,
Hye Kyung Kim2 College of Pharmacy, Kyungsung University, Busan
,
Bo Ram Choi1 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
,
Keshab Kumar Karna1 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
,
Jae Hyung You1 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
,
Jai Seong Cha1 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
,
Yu Seob Shin1 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
,
Sung Won Lee3 Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Seoul
,
Chul Young Kim4 College of Pharmacy, Hanyang University, Ansan, Republic of Korea
&
Jong Kwan Park1 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, JeonjuCorrespondence[email protected]
 show all
Pages 3959-3968 | Published online: 12 Dec 2016

Figures & data

Table 1 Dose-dependent effects of cisplatin on body, testicular, epididymis, seminal vesicle, prostate and kidney weights

Table 2 Dose-dependent effects of cisplatin on sperm count, motility, and apoptosis

Table 3 Dose-dependent effects of cisplatin on ROS/RNS and MDA in blood plasma

Table 4 Dose-dependent effects of cisplatin on RBC count, hemoglobin, and hematocrit

Figure 1 Effect of cisplatin on testosterone and testicular tissue.

Notes: (A) Total testosterone level; (B) Western blot of StAR protein; (C) StAR protein. Data are expressed as mean ± standard error. *P<0.001 versus control group, #P<0.05 versus control group.
Abbreviations: CIS-2, cisplatin 2 mg/kg i.p.; CIS-4, cisplatin 4 mg/kg i.p.; CIS-6, cisplatin 6 mg/kg i.p.; CIS-8, cisplatin 8 mg/kg i.p.; CIS-10, cisplatin 10 mg/kg i.p.; i.p., intraperitoneally; StAR, steroidogenic acute regulatory.
Figure 1 Effect of cisplatin on testosterone and testicular tissue.

Figure 2 Effect of cisplatin on epididymal sperm.

Notes: (A) Western blot of CatSper; (B) CatSper protein. Data are expressed as mean ± standard error. *P<0.001 versus control group, #P<0.05 versus control group.
Abbreviations: CIS-2, cisplatin 2 mg/kg i.p.; CIS-4, cisplatin 4 mg/kg i.p.; CIS-6, cisplatin 6 mg/kg i.p.; CIS-8, cisplatin 8 mg/kg i.p.; CIS-10, cisplatin 10 mg/kg i.p.; i.p., intraperitoneally.
Figure 2 Effect of cisplatin on epididymal sperm.

Figure 3 Effect of cisplatin on endoplasmic reticulum stress markers.

Notes: (A) Western blot of GRP-78; (B) Western blot of ATF; (C) Western blot of pIRE; (D) Western blot of pPERK; (E) GRP-78 protein; (F) ATF protein; (G) pIRE protein; (H) pPERK protein. Data are expressed as mean ± standard error. *P<0.001 versus control group, #P<0.05 versus control group.
Abbreviations: ATF, activating transcription factor; CIS-2, cisplatin 2 mg/kg i.p.; CIS-4, cisplatin 4 mg/kg i.p.; CIS-6, cisplatin 6 mg/kg i.p.; CIS-8, cisplatin 8 mg/kg i.p.; CIS-10, cisplatin 10 mg/kg i.p.; GRP-78, glucose-regulated protein-78; i.p., intraperitoneally; pIRE, phosphorylated inositol-requiring transmembrane kinase/endoribonuclease; pPERK, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase.
Figure 3 Effect of cisplatin on endoplasmic reticulum stress markers.

Table 5 Dose-dependent effects of cisplatin on renal index, BUN, and renal tubular necrosis

Figure 4 Light micrographs of tissue stained with hematoxylin and eosin (×400).

Notes: (A) Kidney; (B) testis.
Figure 4 Light micrographs of tissue stained with hematoxylin and eosin (×400).

Table 6 Dose-dependent effects of cisplatin in spermatogenic cell density and Johnsen’s score of seminiferous tubules

Figure 5 Relation between cisplatin dose-dependent effect on ROS and ER stress.

Abbreviations: ATF, activating transcription factor; ER, endoplasmic reticulum; pIRE, inositol-requiring transmembrane kinase/endoribonuclease; pPERK, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase; ROS, reactive oxygen species.
Figure 5 Relation between cisplatin dose-dependent effect on ROS and ER stress.

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