title: Melatonin alleviates cadmium-induced cellular stress and germ cell apoptosis in testes.
abstract: Increasing evidence demonstrates that melatonin has an anti-apoptotic effect in somatic cells. However, whether melatonin can protect against germ cell apoptosis remains obscure. Cadmium (Cd) is a testicular toxicant and induces germ cell apoptosis. In this study, we investigated the effects of melatonin on Cd-evoked germ cell apoptosis in testes. Male ICR mice were intraperitoneally (i.p.) injected with melatonin (5 mg/kg) every 8 hr, beginning at 8 hr before CdCl(2) (2.0 mg/kg, i.p.). As expected, acute Cd exposure resulted in germ cell apoptosis in testes, as determined by terminal dUTP nick-end labeling (TUNEL) staining. Melatonin significantly alleviated Cd-induced testicular germ cell apoptosis. An additional experiment showed that spliced form of XBP-1, the target of the IRE-1 pathway, was significantly increased in testes of mice injected with CdCl(2). GRP78, an endoplasmic reticulum (ER) chaperone, and CHOP, a downstream target of the PERK pathway, were upregulated in testes of Cd-treated mice. In addition, acute Cd exposure significantly increased testicular eIF2α and JNK phosphorylation, indicating that the unfolded protein response (UPR) pathway was activated by CdCl(2). Interestingly, melatonin almost completely inhibited Cd-induced ER stress and the UPR in testes. In addition, melatonin obviously attenuated Cd-induced heme oxygenase (HO)-1 expression and protein nitration in testes. Taken together, these results suggest that melatonin alleviates Cd-induced cellular stress and germ cell apoptosis in testes. Melatonin may be useful as pharmacological agents to protect against Cd-induced testicular toxicity.
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Ji
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Can
authors.initials: C
authors.lastname: Meng
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Zhao
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Xiu-Hong
authors.initials: XH
authors.lastname: Meng
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005854:Germ Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006651:Histocytochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D000071701:Regulatory Factor X Transcription Factors; D013737:Testis / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D002104:Cadmium; D051547:Heme Oxygenase-1; D008550:Melatonin