Selenium Alleviates Porcine Nephrotoxicity of Ochratoxin A by Improving Selenoenzyme Expression In Vitro

Abstract

Ochratoxin A (OTA), a mycotoxin, is a potent nephrotoxin in humans and animals. Selenium (Se) is an essential micronutrient for humans and animals, and plays a key role in antioxidant defense. To date, little is known about the effect of Se on OTA-induced nephrotoxicity. In this study, the protective effects of selenomethionine against OTA-induced nephrotoxicity were investigated using the porcine kidney 15 (PK15) cells as a model. The results showed that OTA induced nephrotoxicity in a dose-dependent manner. Se at 0.5, 1, 2 and 4 μM had significant protective effects against OTA-induced nephrotoxicity. Furthermore, selenomethionine enhanced the activity and mRNA and protein expression of glutathione peroxidase 1 (GPx1), mRNA expression of GPx4, and mRNA expression of thioredoxin reductase 1 in the presence and absence of OTA. Among them, promoting effect of selenomethionine on GPx1 was maximal. Knock-down of GPx1 by using a GPx1-specific siRNA eliminated the protective effects of selenomethionine against OTA-induced nephrotoxicity. The results suggest that selenomethionine alleviates OTA-induced nephrotoxicity by improving selenoenzyme expression in PK15 cells. Therefore, selenomethionine supplementation may be an attractive strategy for protecting humans and animals from the risk of kidney damage induced by OTA.

Selenium Yeast Alleviates Ochratoxin A-Induced Apoptosis and Oxidative Stress via Modulation of the PI3K/AKT and Nrf2/Keap1 Signaling Pathways in the Kidneys of Chickens

“…OTA is targeted to the kidney and causes nephrotoxicity. It has been reported that Se could alleviate porcine nephrotoxicity of OTA [13]. The use of appropriate Se supplement can enhance antioxidant and immune system functioning, thus promoting disease resistance [14,15].…”

Effects of ochratoxin A on ER stress, MAPK signaling pathway and autophagy of kidney and spleen in pigs

“…4,6,30,31 Many previous studies indicated that OTA-induced toxicity is related to oxidative stress. [10][11][12][13] Although a lot of work has been done in pigs, the effects of OTA on ER stress, autophagy, and MAPK signaling pathway have not been reported until now. The present study is the first time to investigate whether ER stress, autophagy and MAPK signaling pathway were induced by OTA in pigs.…”

“…Many previous studies focus on the effects of OTA on oxidative stress, [10][11][12][13] but few researches are reported about the effects of OTA on ER stress, MAPK signaling pathway and autophagy. It has been reported that ER stress may be basic mechanisms that increase the severity or complicate the condition of oxidative stress.…”

“…9 Many previous studies indicated that OTA-induced toxicity is related to oxidative stress in rabbit kidney, human embryonic kidney cells, human peripheral blood mononuclear cells or porcine kidney cells. [10][11][12][13] It has been reported that mycotoxin patulin or OTA induced human intestinal and kidney cells or mesangial cells cytotoxicity through an oxidative stress-related induction of endoplasmic reticulum (ER) stress. 14,15 However, the effect of OTA on ER stress in pigs has not been reported until now.…”

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

“…Furthermore, genetic toxicology studies provided strong evidence, for OTA-mediated mechanisms, of oxidative damage [13,14]. OTA significantly reduces the expression of genes involved in oxidative stress in the kidney tissues, and many of these genes contain antioxidant regulatory elements (AREs) in their promoter regions [15]. Antioxidant regulatory elements are identified by the transcription factor NF-E2-related factor 2 (NRF2), which regulates genes encoding detoxification, cell protection, and antioxidant enzymes [16].…”