Aşılarda Kullanılan Koruyucu ve Adjuvan Maddelerin Olası Toksik Etkilerinin Değerlendirilmesi

Abstract

The World Health Organization defines vaccines as “pharmaceutical products that enable our immune system to recognize and fight pathogens such as viruses and bacteria and protect our body against the diseases caused by them”. Vaccines save millions of lives each year. However, discussions about the safety of vaccine components continue, leading to "vaccine rejection" or “vaccine hesitancy”. There are serious concerns about the safety of aluminum compounds used as adjuvant and thiomersal used as preservative in vaccines. In this thesis, we aimed to evaluate the possible toxic effects of seperatedly or combined applied thiomersal and aluminum in SH-SY5Y cell line by comparing with the control group. The cytotoxic effects of thiomersal and aluminum were evaluated; inhibitory concentration 20 (IC20) was determined as 1.15 µM for thiomersal and 362 µM for aluminum. Afterwards, thiomersal and aluminum were applied to the cells separately and together at the dose of IC20 for 24 hours. Oxidative stress parameters, DNA damage, NRF2 protein levels, neurotransmitter levels (dopamine, norepinephrine) and dopamine transporter protein levels were measured after IC20 concentration of these compounds were applied for 24 hours. Intracellular reactive oxygen species (ROS) levels increased significantly in cells treated with aluminum and aluminum+thiomersal. Total GSH levels decreased in the aluminum administered group. Total antioxidant capacity (TAOC) and protein oxidation levels increased significantly in the aluminum-treated and aluminum+thiomersal- administered groups. Lipid peroxidation increased in a statistically significant way in the groups treated with aluminum and aluminum+thiomersal. NRF2 levels and DNA damage were found to be significantly higher in all treatment groups. While dopamine levels increased significantly in cells treated with thiomersal and aluminum+thiomersal, DAT levels were found to be higher in all experimental groups compared to the control. Norepinephrine levels did not change significantly in the experimental groups. These findings show that both thiomersal and aluminum can change the oxidant/antioxidant status in neuroblastoma cells and cause DNA damage. In addition, thiomersal and/or aluminum have a significant modifiying effect on dopamine and DAT in neuroblastoma cells. When a general evaluation is made, it can be stated that the changes observed in cells treated with aluminum + thiomersal are more pronounced. In some vaccines, including vaccines for influenza, both compounds are present although rarely. Therefore, care should be taken in vaccinations, especially in sensitive populations such as infants and children, and safer alternatives of thiomersal and aluminum compounds should be developed.