ZIKA: Mouse Study Finds Antioxidant Ebselen Reduces Risk of Sexual Transmission

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Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth. Wikipedia image

Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth.
Wikipedia image

Yogy Simanjuntak PhD
Postdoctoral Research Fellow
Institute of Biomedical Sciences
Academia Sinica, Taiwan 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite the low case fatality, Zika virus infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Primarily transmitted by Aedes species mosquitoes, Zika also can be sexually transmitted in humans. By August 2016, the sexual transmission of Zika had been documented in 11 countries worldwide and most of the cases were from male to female. Infectious Zika in semen has been reported. Moreover, unlike in serum or urine samples, Zika RNA can still be detected in semen up to 188 days after the onset of symptoms. In the absence of approved antiviral drugs or vaccines for Zika infection, preventing the disease transmission is critical.

We observed Zika progressively damaged testes by gaining access to testicular cells including sperm. Notably, Zika caused signs of increased testicular oxidative stress and inflammation, characterized by high levels of reactive oxygen species and pro-inflammatory cytokines. Our data indicate that these factors may contribute to testicular damage as well as successful sexual transmission of Zika; thus, we speculate antioxidants might display beneficial effects to alleviate these disease outcomes.

We found that antioxidant ebselen both alleviated testicular damage and prevented sexual transmission of Zika via sperm from infected male mice to uninfected female mice.

MedicalResearch.com: What should readers take away from your report? 

Response: Infection of Zika in male reproductive system brings several consequences including damage of testes, infertility, and disease transmission via semen. Zika increases testicular oxidative stress and inflammatory response that may play a role as a key factor attributed to testicular damage and successful sexual transmission of Zika. Therefore, by controlling this factor in testes, antioxidants that display a unique property such as ebselen may effectively alleviate testicular damage and prevent sexual transmission of Zika. 

MedicalResearch.com: What are the unique properties of ebselen in this study?

Response: We found ebselen greatly reduced Zika load in testes and brain, but not in the spleen. Ebselen catalyzes the reduction of reactive oxygen species in a mode similar to glutathione peroxidase-4, an antioxidant enzyme highly expressed in spermatogenic cells. Interestingly, this enzyme also plays a role in brain development and neuronal survival. Therefore, EBS may have beneficial properties for the treatment of testicular pathology while more effective testis-specific drugs or antioxidants remain to be discovered.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: The implication of glutathione peroxidase-4 in female reproduction remains unknown and further studies to evaluate whether ebselen may alleviate the impacts of Zika in female reproductive system are warranted.

In addition, correlation study and regression modeling are required to determine whether the level of oxidative stress and inflammatory cytokines can be a predictor of successful sexually transmitted Zika. It has recently become apparent that semen acts directly on tissues in the female reproductive tract. A substantial level of seminal pro-inflammatory cytokines and reactive oxygen species may provoke inflammatory responses in the female reproductive tract and cause tissue injury. Consequently, these processes may create access to and favorable conditions for infectious Zika in semen to establish an initial infection in the female reproductive tract.

Lastly, antioxidants have been used to improve the prognosis of viral diseases. However, the dosage and treatment duration of antioxidant as a therapeutic agent must be carefully interpreted. Antioxidants have beneficial effects at a physiologic dose but at a relatively high dose, they may have unfavorable effects.

Citations:

Yogy Simanjuntak, Jian-Jong Liang, Si-Yu Chen, Jin-Kun Li, Yi-Ling Lee, Han-Chung Wu, Yi-Ling Lin. Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission. PLOS Pathogens, 2018; 14 (2): e1006854 DOI: 10.1371/journal.ppat.1006854 

 

 

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