Abstract
Ochratoxin-A (OTA) is a mycotoxin that is a common contaminant of food products for both humans and animals. This mycotoxin has several toxic effects. In particular, ochratoxin has significant nephrotoxic potential. In fact, OTA has been described as being responsible for naturally occurring animal and human kidney disorders. The toxicity of this mycotoxin involves the induction of the oxidative stress pathways. Therefore, in the present study, we wanted to evaluate the potential protective effects of hydroxytyrosol (HT), a phenolic constituent with potent antioxidant activity, of extra virgin olive oil in three different renal cell lines, the Madin-Darby canine kidney cell line (MDCK), a pig kidney cell line (LLC-PK1), and a rabbit kidney cell line (RK 13), and in rats. Our results clearly showed that renal cells respond to OTA exposure by reducing cell proliferation and the induction of oxidative stress. Pre-incubation of the cells with HT prevented the cellular cytotoxicity and increased reactive oxygen species (ROS) levels induced by OTA. In addition, the antioxidative activity of HT was studied by measuring malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels and nitrosative stress. Finally, we investigated the capability of HT (20 mg/kg, intraperitoneally) to act in vivo. In rats, HT reduced oxidative stress and collagen accumulation in the kidney and counteracted the augmentations in AST, ALT, and creatinine levels following OTA induction (250 μg/kg for 90 days orally). In conclusion, our findings demonstrate that HT is able to protect three renal cell lines from the damage induced by OTA and protect the kidneys of rats. Therefore, the use of this compound could be an important strategy for the treatment and prevention of this type of kidney dysfunction.
Highlights
Mycotoxins are natural products characterized by a low molecular weight that are made as secondary metabolites by filamentous molds or fungi
We evaluated the effects of diverse OTA concentrations (2.5, 5, 15, 25 μg/mL) on the viability of LLC-PK1, Madin-Darby canine kidney cell line (MDCK), and RK 13 cells 24 h after treatment
By MTT assay, we demonstrated that the number of live cells notably diminished with increasing concentrations of OTA
Summary
Mycotoxins are natural products characterized by a low molecular weight that are made as secondary metabolites by filamentous molds or fungi. Examples of mycotoxins of the utmost public health and agro-economic importance include fumonisins (Fs), trichothecenes, ochratoxins (OTs), zearalenone (ZEN), and aflatoxins (AFs) [2]. These toxins represent a serious worldwide issue in terms of animal and human health and condemned agricultural products [3]. Current investigations have correspondingly demonstrated beneficial effects of HT on the liver, where olive oil phenols impede the synthesis of cholesterol, triglycerides, and lipids [15, 16] It has been described in epidemiological reports that dietary consumption of foods rich in antioxidants, such as phenolic compounds, is linked with a reduced risk of renal dysfunction [17]. We performed our research on three different cell lines [LLC-PK1 (pig kidney cell line, proximal tubule epithelial cells), MDCK (Madin-Darby canine kidney cell line, distal tubule epithelial cells), and RK 13
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