Abstract
Abstract in English, Croatian Considering that research of adverse effects of mono(2-ethylhexyl) phthalate (MEHP) and monobutyl phthalate (MBP), two key metabolites of the most common phthalates used as plasticisers in various daily-life products, has been scattered and limited, the aim of our study was to provide a more comprehensive analysis by focusing on major organ systems, including blood, liver, kidney, and pancreas in 66 male pubertal rats randomised into eleven groups of six. The animals were receiving either metabolite at doses of 25, 50, 100, 200, or 400 mg/kg bw a day by gavage for 28 days. The control group was receiving corn oil. At the end of the experiment, blood samples were collected for biochemical, haematological, and immunological analyses. Samples of kidney, liver, and pancreas were dissected for histopathological analyses. Exposure to either compound resulted in increased liver and decreased pancreas weight, especially at the highest doses. Exposed rats had increased ALT, AST, glucose, and triglyceride levels and decreased total protein and albumin levels. Both compounds increased MCV and decreased haemoglobin levels compared to control. Although they also lowered the insulin level, exposed rats had negative islet cell and insulin antibodies, same as control. Treatment-related histopathological changes included sinusoidal degeneration in the liver, glomerular degeneration in the kidney, and degeneration of pancreatic islets. Our findings document toxic outcomes of MEHP and MBP on endocrine organs in male pubertal rats but also suggest the need for additional studies to better understand the mechanisms behind adverse effects in chronic exposure. Budući da su ograničene spoznaje o štetnim učincima mono(2-etilheksil) ftalata i monobutil ftalata, dvaju ključnih metabolita najčešćih ftalata koji se rabe u izradi plastike u različitim proizvodima za svakodnevnu primjenu, cilj je našeg istraživanja bio dobiti potpuniju sliku o njima s obzirom na organske sustave, uključujući krv, jetru, bubreg i gušteraču u 66 mužjaka štakora u pubertetu, nasumce raspoređenih u jedanaest skupina po 6 životinja, od kojih su neke gavažom primale jedan od tih dvaju metabolita 28 dana u dozama od 25, 50, 100, 200 ili 400 mg/kg tjelesne mase na dan. Kontrolna je skupina primala samo kukuruzno ulje, koje je u drugim skupinama služilo kao otapalo za metabolite. Na kraju pokusa prikupljeni su uzorci krvi za biokemijske, hematološke i imunološke pretrage. Uzorci bubrega, jetre i gušterače uzeti su disekcijom za histopatološku analizu. Izloženost bilo kojemu od tih dvaju metabolita dovela je do povećanja mase jetre i smanjenja mase gušterače, posebice pri najvišim dozama. Izloženi štakori imali su povišene vrijednosti ALT, AST, glukoze i triglicerida te snižene vrijednosti ukupnih proteina i albumina u krvi. Oba su metabolita dovela do povećanja prosječnog volumena eritrocita (MCV) i pada hemoglobina u usporedbi s kontrolnom skupinom. Premda su doveli i do pada razina inzulina u krvi, nalazi na antitijela na stanice Langerhansovih otočića i inzulin u izloženih štakora bili su negativni, baš kao i u kontrolnoj skupini. Histopatološke promjene povezane s izloženosti obuhvaćale su sinusoidnu degeneraciju u jetri, glomerulsku degeneraciju u bubregu te degeneraciju otočića gušterače. Naši rezultati potvrđuju toksično djelovanje MEHP-a i MBP-a na endokrine organe mužjaka štakora u pubertetu, ali isto tako upućuju na potrebu za daljnjim istraživanjima ne bi li se bolje razumjeli mehanizmi koji stoje iza štetnih događaja, naročito pri kroničnoj izloženosti ftalatima.