Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-induced cell damage in a human hepatoma cell line (Hep G2).
Recent findings have suggested that oxidative damage might contribute to the cytotoxicity and carcinogenicity of aflatoxin B(1) (AFB(1)). 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 AFB(1) 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 AFB(1)-induced cell damage. In particular, 24-h pretreatment with 50 micro M Ros A inhibited the cytotoxicity of 10 micro M AFB(1) (by 45%) and 10 micro M 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).
Department of Pharmacology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
C
C
Renzulli
F
F
Galvano
L
L
Pierdomenico
E
E
Speroni
M C
MC
Guerra
D016604:Aflatoxin B1 / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D053630:Depsides; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D009793:Ochratoxins / Q000633:toxicity*; D014176:Protein Biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D000097123:Rosmarinic Acid
D016604:Aflatoxin B1; D000975:Antioxidants; D053148:Caspase 3; D020169:Caspases; D002934:Cinnamates; D004247:DNA; D053630:Depsides; D009793:Ochratoxins; D017382:Reactive Oxygen Species; D000097123:Rosmarinic Acid; C025589:ochratoxin A; C505407:CASP3 protein, human