Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-

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http://www3.interscience.wiley.com/cgi-

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Journal of Applied Toxicology

Volume 24, Issue 4 , Pages 289 - 296

Published Online: 3 Aug 2004

Copyright © 2004 Wiley & Sons, Ltd.

Research Article

Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-

induced cell damage in a human hepatoma cell line (Hep G2)

C. Renzulli 1, F. Galvano 2, L. Pierdomenico 3, E. Speroni 1, M. C.

Guerra 1 *

1Department of Pharmacology, University of Bologna, via Irnerio 48,

40126 Bologna, Italy

2Department of Agroforestry, Environmental Science and Technology,

University of Reggio Calabria, Piazza San Francesco 7, Reggio

Calabria, Italy

3Institute of Histology and General Embryology, University of

Bologna, via Belmeloro 8, Bologna, Italy

email: M. C. Guerra (mcguerra@...)

*Correspondence to M. C. Guerra, Department of Pharmacology,

University of Bologna, via Irnerio 48, 40126 Bologna, Italy.

Funded by:

MURST

PRIN; Grant Number: Cofin 2000

Keywords

aflatoxin B1 • ochratoxin A • rosmarinic acid • Hep G2 cells •

cytotoxicity

Abstract

Recent findings have suggested that oxidative damage might

contribute to the cytotoxicity and carcinogenicity of aflatoxin B1

(AFB1). The induction of oxidative stress also plays an important

role in the toxicity of another mycotoxin: ochratoxin A (OTA). In

this study, the protective effect of rosmarinic acid (Ros A) against

AFB1 and OTA-induced cytotoxicity was investigated in a human

hepatoma-derived cell line (Hep G2). Rosmarinic acid, a natural

phenolic compound contained in many Lamiaceae herbs such as Perilla

frutescens, sage, basil and mint, inhibits complement-dependent

inflammatory processes and may have therapeutic potential.

The ability of Ros A to reduce radical oxygen species (ROS)

production, protein and DNA synthesis inhibition and apoptosis

caused by the two mycotoxins was also investigated. Our experiments

proved the significant cytoprotective effect of Ros A in vitro from

OTA- and AFB1-induced cell damage. In particular, 24-h pretreatment

with 50 µM Ros A inhibited the cytotoxicity of 10 µM AFB1 (by 45%)

and 10 µM OTA (by 35%) in Hep G2 cells (P < 0.001). Moreover, Ros A

dose dependently attenuated ROS production and DNA and protein

synthesis inhibition induced by both of the toxins. Similarly,

apoptosis cell death was prevented, as demonstrated by reduction of

DNA fragmentation and inhibition of caspase-3 activation (P <

0.001). Copyright © 2004 Wiley & Sons, Ltd.

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Received: 4 December 2003; Accepted: 22 March 2004

Digital Object Identifier (DOI)

10.1002/jat.982 About DOI