Abstract
Toxoplasma gondii is an opportunistic parasite that can cause severe disorders in infants and pregnant women and can also be lethal in immunologically compromised individuals. During unfit host immune conditions, and as a consequence to latent stage opportunity, the protozoan stimulates serious infection, and signifies higher morbidity and mortality including humans with Acquired Immuno-Deficiency Syndrome (AIDS) or those receiving corticosteroids and cancer chemotherapy. Tamoxifen drug (TAM) is a selective estrogen receptor modulator (SERM), which is commonly used for treatment of breast cancer; it has a known immunomodulatory effects on the patient, especially if administered for a long time as happens in cases of post breast cancer surgery and anti-recurrence prophylactic measures where women might persist to take TAM for years. The research question here was: Can TAM reactivates latent toxoplasmosis? To assess the possible stressful effect of TAM, rats were experimentally infected by T. gondii (RH strain). Three months later, they were treated by oral administration of TAM (10 mg/kg body weight/day) for 7, 14, 21 and 28 days. Tamoxifen effect on toxoplasmosis dynamics was estimated by counting Toxoplasma brain cysts and serological detection of anti-parasitic IgM and IgG all through the experiment time. The results showed an initial insignificant decrease in parasitic burden in groups treated for one week followed by a significant increase in groups treated for 14, 21 and 28 days. There was also a significant decrease in IgM titers in groups treated for one and two weeks while there was a significant increase in IgM titers in groups treated for three and four weeks. There was a significant increase in IgG titrers in groups treated for 14 and 21 days and a border line significant increase in the 1st week while there was non-significant increase in 4th week. Key words: Toxoplasmosis, tamoxifen, breast cancer, serological, Toxoplasma brain cysts, immunomodulatory.
Highlights
The results showed that there was a decrease in average brain parasitic load (ABPL) in Tamoxifen drug (TAM) infected and treated (IT) group for one week as compared to the infected untreated (IU) control group (3.4%), the difference was statistically non-significant (p = 0.448)
CD4+ T cells are critical for avoiding reactivation of latent toxoplasmosis, as the emergence of severe toxoplasmosis is concomitant with the decline in T cell numbers in patients infected with HIV (Luft et al, 1984; Israelski and Remington, 1988) and in mouse models, the lack of CD4+ T cells is associated with increased susceptibility of reactivation during the chronic stage of infection (Johnson and Sayles, 2002)
Tamoxifen (TAM) is a broadly known anti-estrogen, which has been used in adjuvant treatment of early stage, estrogen-sensitive breast cancer for over 20 years, especially for women who still have significant ovarian estrogenic activity which could not be controlled by aromatase inhibitors
Summary
Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis and one-third of the world population had. Breast cancer is the most common malignancy in women around the world. Treatment with TAM lowers the risk of breast cancer recurrence and lowers the risk of death from breast cancer (Early Breast Cancer Trialists' Collaborative Group, 2011). Since both toxoplasmosis and breast cancer are widely distributed globally, the research question was: Could tamoxifen treatment lead to reactivation of latent primary toxoplasmosis? We treated toxoplasmosis experimentally infected rats with TAM for different periods and observed the possible stressful effects of it on Toxoplasma parasitosis Since both toxoplasmosis and breast cancer are widely distributed globally, the research question was: Could tamoxifen treatment lead to reactivation of latent primary toxoplasmosis? For that purpose, we treated toxoplasmosis experimentally infected rats with TAM for different periods and observed the possible stressful effects of it on Toxoplasma parasitosis
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