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Benoxaprofen Modified Liver Proteins In Mice And Rats After A Single Treatment

Sharida Fakurazi, (2004) Benoxaprofen Modified Liver Proteins In Mice And Rats After A Single Treatment. Malaysian Journal of Pharmaceutical Sciences, 2 (1). pp. 21-37. ISSN 16575-7319

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Official URL: http://www.pha.usm.my/pharmacy/Webpage%20journal/abstract/2.1-3.pdf

Affiliations

Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Biomedical Sciences.

Abstract

Earlier studies have proposed that the formation of protein adduct may have a role in the mechanism of hepatotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs).
The objective of the present study was to investigate the pattern of protein adducts induced by a hepatotoxic NSAID,
benoxaprofen ]BNP, Operan (UK); Oraflex (USA)] in mice and rats after single dose. To investigate this further, specific potyclonal antibody has been raised in rabbits against BNP-modified keyhole limpet haemocyanin. Antibody titres from different bleeds were monitored by Enzyme-Linked
Immunosorbent Assay (ELISA) and the specificity and sensitivity of the antibody were characterised further by SDS-PAGE and immunoblotting. Mice and rats were given single doses of BNP; their liver were excised, and subcellular fractions were prepared by differential centrifugation. The subcellular fractions were subjected to SDS-PAGE and probed for BNP-adducts by immunoblotting.
In addition, liver sections were examined histologically and adducts localisation by immunohistochemistry. Various protein adducts ranging from 60 — 200 kDa were detected with a single major adduct of 110 kDa, observed in the 600 x g fraction that were expressed in a dose
dependent manner. In mice, these adducts were found to be localised in the bile canalicular membrane regions of the liver. However, in rats, they were found in the nuclei of the hepatocytes. Hepatotoxicity was not observed in both mice and rats although formation of protein adducts were
observed. These data suggested that hepatotoxicity is not simply triggered by adduct formation per se. Additional events are required before toxicity becomes apparent.

Item Type:Journal
Additional Information:I would like to acknowledge J. Caldwell and R.D. Goldin for their effort and support in running this project. I am thankful to UPM for their financial support in carrying out this project.
Keywords:Benoxaprofen, Hepatotoxicity, Protein Adducts
Subjects:R Medicine, Dentistry, Pharmacy, Nursing
ID Code:6921

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