Overexpression of glutathione peroxidase-1 attenuates cocaine-induced reproductive dysfunction in male mice by inhibiting nuclear factor κB

Publication date: Available online 3 May 2019Source: Chemico-Biological InteractionsAuthor(s): Huynh Nhu Mai, Yoon Hee Chung, Eun-Joo Shin, Ji Hoon Jeong, Tae Woo Jung, Naveen Sharma, Xin Gen Lei, Seung-Yeol Nah, Choon-Gon Jang, Dae-Joong Kim, Boo-Keun Yang, Hyoung-Chun KimAbstractSince reproductive toxicity is associated with oxidative stress, nuclear factor κB (NFκB), a redox-sensitive transcription factor, may be involved in the reproductive dysfunction induced by the abusive drug, such as cocaine. In the present study, we investigated whether NFκB mediates cocaine-induced reproductive dysfunction in male mice, and whether glutathione peroxidase (GPx)-1, a well-known enzymatic antioxidant, modulates NFκB activity to affect this reproductive dysfunction. Cocaine treatment significantly increased nuclear translocation of NFκB and its DNA binding activity in the testis of mice. Treatment with cocaine resulted in a significant increase in sperm abnormality, and in significant decreases in the sperm viability and sperm level. Furthermore, cocaine significantly reduced hypothalamic gonadotropin-releasing-hormone expression and plasma testosterone level. These alterations were more pronounced in the GPx-1 knockout (GPx-1 KO) than wild type (WT) mice, and they were less pronounced in GPx-1 overexpressing transgenic (GPx-1 TG) than in non-transgenic (non-TG) mice. Pyrrolidine dithiocarbamate (PDTC), an NFκB inhibitor, was more effective in attenuating cocaine-induced reproduc...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research