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Cytotoxicity induced by fumonisin B1, beauvericin and ochratoxin A in porcine kidney PK15 cells: effects of individual and combined treatment on lipid peroxidation and glutathione levels

Fumonisin B1 (FB1), beauvericin (BEA) and ochratoxin A (OTA) are world-spread mycotoxins that naturally co-occur in maize. FB1 and OTA could be implicated in development of various diseases in animals and humans, including nephrotoxicosis and carcinogenesis. Both of them enhance lipid peroxidation in hepatocytes, kidney cell lines, and rat liver and kidney. BEA increases ion permeability in biological membranes by forming a complex with essential cations (Ca2+, Na+, K+) and/or by forming cation-selective channels in lipid membranes, which may affect ionic homeostasis. Save for the known impairment of antioxidative status in plants, BEA has not been investigated yet for inducing lipid peroxidation and cytotoxicity in kidney cells. Therefore, the objectives of this study were to determine individual and combined effects of FB1, BEA and OTA on PK15 cells by measuring cell viability, lactate dehydrogenase activity (LDH), lipid peroxidation (TBARS) and intracellular glutathione (GSH) level. Cells were treated with 0.05, 0.5 and 5  g/ml of mycotoxin alone or with combination of two or all three mycotoxins for 24 and 48 h. Changes in cell viability, LDH activity, TBARS and GSH levels showed that the cytotoxic effects of these mycotoxins were concentration- and time- dependent. Single FB1, BEA and OTA significantly reduced cell viability (to 75%, 68% and 65% of control value respectively) after 24 h exposure to 5  g/ml, without significant changes in LDH activity. However, significant increase of LDH activity was observed after 48 h of exposure to the same concentration of FB1 (45%), BEA (84%) and OTA (77%), in respect to control. After 24 h, none of mycotoxins given alone significantly increased the concentration of TBARS, except OTA in the highest concentration (56%). FB1 and BEA significantly increased TBARS (57 and 80 %, respectively) only when the highest dose was applied for 48 h. However, GSH was significantly decreased after 24 h exposure to 0.05  g OTA/ml (18%), while FB1 and BEA significantly decreased GSH (approximately 13%) at the concentration of 0.5  g/ml. Combined treatment with two or three mycotoxins resulted mostly in additive effects, although a synergistic interaction could not be excluded. Our results show that simultaneous prolonged exposure to FB1, BEA and OTA in lower dietary concentrations could decrease antioxidative defence and increase the rate of kidney cell damage.

Combined treatment; kidney cells; mycotoxins; oxidative stress

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