RIZA NOVIERTA PESIK, 099913278M (2002) EKSPRESI p53 PADA APOPTOSIS SEL EPITEL MUKOSA LAMBUNG TIKUS PUTIH WYISTAR DENGAN INDUKSI LNDO_METI{ACLN : DAYA PROTEKSI KOMBIINASI VITAMIN E DAN p KAROTEN. Thesis thesis, UNIVERSITAS AIRLANGGA.

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Abstract

BACKGROUND : Apoptosis is the process of programmed cell death characterized by a series of distinct biochemical and morphological changes. The generation of reactive oxygen species is critically involved in indomethacin-induced apoptosis in gastric epithelial cells. Here, we investigated the expression of p53 associated with gastric epithelial cells apoptosis during indomethacin-induced gastric mucosal injury; and evaluated the protective effect of antioxidants vitamins E and 13-carotene combination on this process. METHODS: The experiments were conducted with groups of rats treated intragastric doses of antioxidants vitamins E and 13-carotene combination at 12mg/450µg (PO; 24mg/900µg (P2); 36mg/1350ug (P3), followed by an intragastric dose of indomethacin at 60mg/kg. The animals were killed 2 h later and their gastric mucosal tissue of the corpus area used for assays of epithelial cells apoptosis by terminal deoxyuridine nucleotide nick end labeling (TUNEL), and the p53 expressions by immunohistochemistry. RESULTS: The analysis of variance showed that there was significantly [p<0,05 ] different in the number of apoptosis and p53 expressions. In the absence of antioxidants vitamins E and (3-carotene combination (Po), indomethacin caused an increase in the epithelial cells apoptosis (6.875%) and the p53 expressions (39.250%). Treatment with antioxidants vitamins E and 13-carotene combination produced a decrease in the epithelial cells apoptosis (P1=3.500%; P2=3.125%; P3=2.500%) and the p53 expressions (P1=19.750%; P2=10.875%; P3=7.750%). CONCLUSIONS: The results implicate p53 in the process of indomethacininduced gastric epithelial cells apoptosis, and point towards participation of the generation of reactive oxygen species in the amplification of the cell death signaling cascade. Our fording also show that antioxidants vitamins E and [3-carotene combination protection against gastric mucosal injury caused by indomethacin involves the suppression of the apoptotic events propagated by p53.

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