Günlük Hayatta Sıklıkla Kullanılan Fitalatların Metabolitleri Mono Etil Hekzil Fitalat (Mehp) Ve Mono Bütil Fitalatın (Mbp) Olası Etkilerinin in Vıvo ve In Vıtro Yöntemlerle Araştırılması

Abstract

Endocrine disruptors are chemicals that have significant effects on the living organism by altering, inhibiting, or mimicking the effects of hormones synthesized by the endocrine system Phthalates are one of the main endocrine disrupting chemicals. The incidence of diabetes has almost tripled in the past 10 years. In the following 20 years, the number of patients with diabetes diagnosis is thought to exceed 300 million. It seems likely that endocrine disruptors are associated with diabetes, given their relationship to reproduction, metabolism, and adipose tissue. Di butyl phthalate (DBP) and Di-Ethylhexyl phthalate (DEHP) are the most widely used phthalates. In mammals, the absorption and metabolism of phthalates are quite rapid and conducted studies showed that most of the metabolites formed have been more toxic than the main chemical. Therefore, in vivo and in vitro effects of mono 2-ethyl hexyl phthalate (MEHP) and monobutyl phthalate (MBP), metabolites of the most exposed phthalates (DEHP and DBP) were examined in this study. For this reason, INS-1 β cells were exposed to MEHP and MBP metabolites at 5 different concentrations (such as 0.001 μM, 0.01 μM, 0.1 μM, 1 μM or 10 μM) and 3 different times like 24h, 48h and 72h. their effect at the end of the hour was demonstrated by the MTT cytotoxicity test. Total oxidant and antioxidant levels were also measured. The mRNA expression levels of FOXO-1 and PDX- 1 genes in relation to beta cell proliferation, SIRT-1,Insulin-1 and Insulin-2 genes in relation to Beta cell functions, and p53, Bcl-2 and Bcl-xL genes in relation to apoptosis were analyzed. Insulin released from INS-1 cells was measured. In the results, A statistical decrease in cell viability was observed due to increased dose for MEHP and MBP. The amount of insulin secreted from the cells decreased after MEHP and MBP applications compared to the control group. Total oxidant levels increased as a result of both MEHP and MBP administration depending on time. Total antioxidant levels have been reduced. In the study, there were 11 groups, including 1 oil control group, 5 MEHP (mono 2-Ethylhexyl phthalate) dose administration groups and 5 MBP (mono butyl phthalate) dose administration groups with 6 rats in each group. A total of 66 animals, consisting of 6-week-old male rats, were used. As for the MEHP application groups; the first group was received 25 mg/kg/day of MEHP, second group was received 50 mg/kg/day of MEHP, the third group was received 100 mg/kg/day of MEHP, the forth group was received 200 mg/kg/day of MEHP and the fifth group was received 400 mg/kg/day of MEHP through oral gavage every morning for 28 days. As for the MBP application groups; the first group was received 25 mg/kg/day of MBP each morning, second group was received 50 mg/kg/day of MBP each morning, third group was received 100 mg/kg/day of MBP each morning, the forth group was received 200 mg/kg/day of MBP each morning and the fifth group was received 400 mg/kg/day of MBP each morning through oral gavage for 28 days. During the experiment, body weights were measured in addition to feed and water consumption in rats. For biochemical analyses, Alanine aminotransferase (ALT), aspartate transaminase (AST), urea, triglycerides, glucose, creatinine, total protein were measured in serum samples taken from rats at the end of the experiment. Insulin hormone mesurement and hematologic analyses were performed in the blood at the end of the experiment. In addition, histopathological examinations were carried out on pancreatic, liver and kidney tissues. Insulin hormone was decreased in 200 and 400 mg/kg/day of MEHP dose groups compared to oil control groups of 25 and 50 mg/kg/day of MEHP. There was also a decrease in the amount of insulin in the MBP dose groups compared to the fat control group. ALT and AST enzymes, triglycerides and glucose measurements increased in the 100, 200 and 400 mg / kg / day MEHP and MBP dose groups. In the 200 and 400 mg / kg / day MEHP dose group, sinusoidal degeneration in the liver, glomerulus degeneration in the kidney, degeneration in the islets of langerhans in the pancreas were observed. Sinusoidal degeneration was observed in the liver in the 400 mg / kg / day MBP dose group. According to the results, MEHP and MBP caused a negative effect on pancreatic β cells and pancreas.