PMID- 31306659 OWN - NLM STAT- MEDLINE DCOM- 20191007 LR - 20191007 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 232 DP - 2019 Sep 1 TI - MitoQ ameliorates testicular damage induced by gamma irradiation in rats: Modulation of mitochondrial apoptosis and steroidogenesis. PG - 116655 LID - S0024-3205(19)30581-8 [pii] LID - 10.1016/j.lfs.2019.116655 [doi] AB - AIMS: The deleterious effect of gamma radiation on testicular tissue is a challenging problem in nuclear medicine. This study investigated the potential radioprotective effect of mitoquinol (MitoQ), a mitochondria-targeted antioxidant, against testicular damage induced by gamma irradiation in rats. MAIN METHODS: Rats were allocated into four groups. The first group served as the control, the second group received MitoQ (2 mg / kg / day; i.p.) for seven days, the third group was exposed to gamma radiation (5 Gy as a single dose) and the last group received MitoQ prior to irradiation. Rats were sacrificed. Then, sperm analyses and the serum testosterone were determined. Moreover, evaluation of mitochondrial oxidative stress parameters (SOD, GSH and GPx) as well as apoptosis indicators (cytochrome-c, Bax, Bcl-2 and caspase-3) was performed. Additionally, analysis of steroidogensis biomarkers (StAR, 3beta-HSD and 17beta-HSD) and histopathological investigations were carried out. KEY FINDINGS: MitoQ replenished mitochondrial SOD, GPx and GSH indicating its strong antioxidant effect in addition to its energy preservation manifested by the elevated ATP. MitoQ inhibited the intrinsic apoptosis via diminution of Bax, cytochrome-c and caspase-3 and alleviation of Bcl-2. This antioxidant conferred protection to steroidogenesis as verified by the increase in testosterone and the up-regulation of StAR, 3beta-HSD and 17beta-HSD expression; these effects might be correlated with its antioxidant/anti-apoptotic potential. Histopathological and sperm analyses corroborated the biochemical findings. SIGNIFICANCE: This study identifies MitoQ as a novel agent for the management of testicular toxicity induced by gamma irradiation. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Ibrahim, Ayman A AU - Ibrahim AA AD - Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, P. O. Box 29, Nasr City, Cairo 11787, Egypt. Electronic address: ayman.ibrahim@eaea.org.eg. FAU - Karam, Heba M AU - Karam HM AD - Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, P. O. Box 29, Nasr City, Cairo 11787, Egypt. FAU - Shaaban, Esmat A AU - Shaaban EA AD - Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, P. O. Box 29, Nasr City, Cairo 11787, Egypt. FAU - Safar, Marwa M AU - Safar MM AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, Suez Desert Road, P.O. Box 43, El Sherouk City, Cairo 11837, Egypt. FAU - El-Yamany, Mohammed F AU - El-Yamany MF AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt. LA - eng PT - Journal Article DEP - 20190713 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Organophosphorus Compounds) RN - 0 (Steroids) RN - 1339-63-5 (Ubiquinone) RN - 65M41NIO61 (mitoquinol) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Apoptosis/drug effects MH - Body Weight/drug effects MH - *Gamma Rays MH - Male MH - Mitochondria/*drug effects/metabolism MH - Organ Size/drug effects MH - Organophosphorus Compounds/*pharmacology MH - Oxidative Stress/drug effects MH - Rats MH - Rats, Wistar MH - Spermatogenesis/drug effects/radiation effects MH - Steroids/*biosynthesis MH - Testis/*drug effects/pathology/*radiation effects MH - Ubiquinone/*pharmacology MH - Whole-Body Irradiation OTO - NOTNLM OT - Gamma radiation OT - Mitochondria-targeted antioxidant OT - Mitochondrial apoptosis OT - Steroidogenesis OT - Testicular damage EDAT- 2019/07/16 06:00 MHDA- 2019/10/08 06:00 CRDT- 2019/07/16 06:00 PHST- 2019/05/17 00:00 [received] PHST- 2019/07/11 00:00 [revised] PHST- 2019/07/12 00:00 [accepted] PHST- 2019/07/16 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2019/07/16 06:00 [entrez] AID - S0024-3205(19)30581-8 [pii] AID - 10.1016/j.lfs.2019.116655 [doi] PST - ppublish SO - Life Sci. 2019 Sep 1;232:116655. doi: 10.1016/j.lfs.2019.116655. Epub 2019 Jul 13.