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Effect of captopril and paraquat on expression of p53 and Bcl-2 genes and proteins in rat lung tissue using RT-PCR and immunohistochemistry

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Author(s): Fouladdel Sh | Mohammadi-Karakani A | Ghazi-Khansari M | Azizi E

Journal: Tehran University Medical Journal
ISSN 1683-1764

Volume: 66;
Issue: 7;
Start page: 456;
Date: 2008;
Original page

Keywords: Paraquat | captopril | rat | toxicity | p53 | Bcl-2

ABSTRACT
"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Paraquat is an herbicide produced and used prevalently worldwide. Studies have shown that lung fibrosis induced by paraquat can be prevented or delayed by certain antioxidants, iron chelating agents, melatonin, and, recently, blood pressure lowering drugs such as captopril."n"n Methods: The protective effects of captopril on paraquat toxicity were studied using RT-PCR and immunohistochemistry to determine the gene and protein expression of p53 and Bcl-2 in lung tissue samples from rats treated with captopril before and after exposure to paraquat."n"n Results: We found no significant difference in the gene and protein expression of p53 in different tissue samples, except for mRNA levels in the lung tissue of captopril-treated rats. However, the protein expression of Bcl-2 is greater in tissue from rats exposed to paraquat alone and paraquat together with pre- and posttreatment with captopril compared to tissue from untreated control rats and from those treated with captopril alone, which can be due to inflammatory responses of lung tissue. By RT-PCR, we were unable to detect Bcl-2 in lung tissue samples."n"n Conclusion: These results show that paraquat does not induce significant DNA damage; therefore, the gene and protein expression of p53 was not changed. Paraquat does induce lung tissue inflammation, which in turn increases Bcl-2 protein expression. Finally, captopril had no significant effect on the lung tissue toxicity induced by paraquat. Considering these results and the cellular interactions in lung tissue, we suggest that complementary assays and in-vitro cell culture experiments be performed to further elucidate the molecular events underlying paraquat lung toxicity. "nKeywords: Paraquat, captopril, rat, toxicity, p53, Bcl-2.
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