Toxicology 242 (2007) 31–38 Available online at www.sciencedirect.com Mycotoxin fumonisin B 1 alters cellular redox balance and signalling pathways in rat liver and kidney Lada Rumora a , Ana-Marija Domijan b,∗ , Tihana ˇ Zani´ c Grubiˇ si´ c a , Maja Peraica b a Faculty of Pharmacy and Biochemistry, Department of Medical Biochemistry and Haematology, Domagojeva 2, 10000 Zagreb , Croatia b Institute for Medical Research and Occupational Health, Unit of Toxicology, Ksaverska cesta 2, 10000 Zagreb , Croatia Received 12 July 2007; received in revised form 3 September 2007; accepted 4 September 2007 Available online 12 September 2007 Abstract Mycotoxin fumonisin B 1 (FB 1 ) is a frequent contaminant of grain, particularly maize, but the mechanism of its toxicity in the kidney and liver is not fully understood. FB 1 -stimulated oxidative stress might disturb cellular redox state and signal transduction pathways of the target cells. In this study we measured total intracellular glutathione (GSH), and assessed mitogen-activated protein kinases (MAPKs) activation and the expression of heat shock proteins (Hsps) Hsp25 and Hsp70 in the liver and kidney of male Wistar rats given 0.5 mg FB 1 /kgb.w. intraperitoneally for 2 or 7 days. The effect of FB 1 on GSH levels, MAPK activation and Hsp expression was found to be related to the type of tissue affected and the length of treatment. In rat liver, cellular GSH content increased, Hsp expression was up-regulated, and ERK and p38 were activated after the 7-day treatment, while even the 2-day treatment sufficed to produce phospho-JNK signal. In rat kidney, GSH levels decreased after the 2- and 7-day treatment with FB 1 , while after the 7-day treatment all three MAPKs were activated, Hsp25 expression increased and Hsp70 expression decreased. In conclusion, FB 1 alters cellular redox balance, which leads to tissue-specific activation and expression of redox-sensitive signalling molecules. It seems that kidney cells are more sensitive to adverse effects of FB 1 . © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Fumonisin B 1 ; Glutathione; Mitogen-activated protein kinases; Heat shock proteins; Liver; Kidney 1. Introduction Mycotoxin fumonisin B 1 (FB 1 ) is a natural contami- nant of grain, particularly maize, all round the world. It is involved in domestic animal diseases such as equine Abbreviations: FB 1 , fumonisin B 1 ; ROS, reactive oxygen species; GSH, glutathione; GSSG, glutathione disulphide; -GCS, -glutamylcysteine synthetase; MAPKs, mitogen-activated protein kinases; Hsps, heat shock proteins; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; HSFs, heat shock transcription factors; HSEs, heat shock elements; ASK1, apoptosis signal-regulating kinase 1; GST, glutathione-S-transferase; AP-1, activator protein-1. ∗ Corresponding author. Tel.: +385 1 4673188; fax: +385 1 4673303. E-mail address: adomijan@imi.hr (A.-M. Domijan). leukoencephalomalacia and porcine pulmonary oedema. In laboratory animals FB 1 is hepatotoxic and nephro- toxic, hepatocarcinogenic in male rats and female mice, and nephrocarcinogenic in male rats. Although exposure to FB 1 in humans is believed to be associated with high incidence of oesophageal cancer in South Africa and primary liver cancer in China, due to the lack of epidemi- ological evidence, International Agency for Research on Cancer (IARC) has classified FB 1 as a possible carcino- gen for humans (Group 2B) (IARC, 2002). It has been shown that FB 1 either stimulates or sup- presses cell proliferation, and might affect cell viability by inducing apoptosis and/or necrosis (Rumora et al., 2002; Stockmann-Juvala et al., 2004). The molecular mechanism of FB 1 toxicity is poorly understood, but 0300-483X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2007.09.006