Nephropathy and hepatopathy in weaned piglets provoked by natural ochratoxin A and involved mechanisms

Zhang, Zheqian; Gan, Fang; Xue, Hang; Liu, Yunhuan; Huang, Da Wei; Khan, Alam Zeb; Chen, Xingxiang; Huang, Kehe

doi:10.1016/j.etp.2015.12.002

Cited by 30 publications

(17 citation statements)

References 57 publications

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“…The reduction of weight gain may be due to less feed intake, less absorption and synthesis in digestive system, more urinary excretion and less reabsorption in kidney . In addition, degenerative changes were observed in the proximal tubular epithelial cells of kidney, consistent with our previous study . Lymphocyte depletion in spleen, peripheral blood lymphocytes and porcine primary splenocytes, IL‐2 concentrations decreasing and TNF‐α concentrations increasing in serum were observed in pigs treated with 400 and 800 μg OTA/kg feed, consistent with previous study in growing pigs .…”

Section: Discussionsupporting

confidence: 91%

“…33,34 In addition, degenerative changes were observed in the proximal tubular epithelial cells of kidney, consistent with our previous study. 31 Lymphocyte depletion in spleen, peripheral blood lymphocytes and porcine primary splenocytes, IL-2 concentrations decreasing and TNF-a concentrations increasing in serum were observed in pigs treated with 400 and 800 lg OTA/kg feed, consistent with previous study in growing pigs. 35 These results demonstrated that OTA induced nephrotoxicity and immunotoxicity in pigs.…”

Section: Discussionsupporting

confidence: 91%

“…It has been reported that OTA contamination levels in human food and pig feed vary from 0 to 1635 μg/kg all around the world . OTA has been identified as a nephrotoxin and immunotoxin in animals and humans . Many previous studies indicated that OTA‐induced toxicity is related to oxidative stress .…”

Section: Discussionmentioning

confidence: 99%

“…[27][28][29] OTA has been identified as a nephrotoxin and immunotoxin in animals and humans. 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.…”

Section: Discussionmentioning

confidence: 99%

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

Gan

Hou

Zhou

et al. 2017

Environmental Toxicology

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Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin and immunotoxin in animals and humans. This research was conducted to evaluate whether endoplasmic reticulum (ER) stress, MAPK signaling pathway and autophagy were induced by OTA in kidney and spleen of pigs. Twenty-seven crossbred pigs randomly allocated to 3 groups were fed for 42 days ad libitum a basal diet without (Con group, 0.00 μg OTA/kg) and with supplementation of OTA at 400 (OTA-L group) and 800 μg/kg (OTA-H group). From each group, 6 pigs were randomly selected for blood collection on days 0, 21, and 42 and 3 pigs were randomly selected for tissue collection on day 42. The results showed that OTA at 400 and 800 μg/kg diets significantly increased OTA concentrations in serum and kidney and spleen induced the histopathological lesions of kidney and spleen, decreased TCR-stimulated T lymphocyte viabilities and IL-2 concentration, increased TNF-α concentration, and decreased T-AOC levels. OTA increased glucose regulated protein 78, p38, and ERK1/2 phosphorylation, and LC3 II and Atg5 protein expression in kidney and spleen of pigs. These results provide new insights into the relationship between OTA and ER stress, p38 and ERK1/2 MAPK signaling pathway and autophagy in pigs.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Gan

Hou

Zhou

et al. 2017

Environmental Toxicology

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“…Biomarkers in the blood are often used to detect kidney damage. UA, BUN, and CRE levels in serum are indicators of kidney health, and elevated levels of UA, BUN, and CRE indicate impaired renal function [38,39]. Our results showed that after OTA exposure, the mice lost weight, their organ coefficient decreased, and their serum UA and BUN levels increased significantly.…”

Section: Discussionmentioning

confidence: 66%

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

et al. 2020

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The present study aimed to investigate the effects of astaxanthin (ASX) on ochratoxin A (OTA)-induced renal oxidative stress and its mechanism of action. Serum kidney markers, histomorphology, ultrastructural observation, and oxidative stress indicators were assessed. Meanwhile, quantitative real-time reverse transcription PCR and western blotting detection of NRF2 (encoding nuclear factor, erythroid 2 like) and members of the NRF2/KEAP1 signaling pathway (KEAP1 (encoding Kelch-like ECH-associated protein), NQO1 (encoding NAD(P)H quinone dehydrogenase), HO-1 (encoding heme oxygenase 1), γ-GCS (gamma-glutamylcysteine synthetase), and GSH-Px (glutathione peroxidase 1)) were performed. Compared with the control group, the OTA-treated group showed significantly increased levels of serum UA (uric acid) and BUN (blood urea nitrogen), tubular epithelial cells were swollen and degenerated, and the levels of antioxidant enzymes decreased significantly, and the expression of NRF2 (cytoplasm), NQO1, HO-1, γ-GCS, and GSH-Px decreased significantly. More importantly, after ASX pretreatment, compared with the OTA group, serum markers were decreased, epithelial cells appeared normal; the expression of antioxidant enzymes increased significantly, NQO1, HO-1, γ-GCS and GSH-Px levels increased significantly, and ASX promoted the transfer of NRF2 from the cytoplasm to the nucleus. These results highlight the protective ability of ASX in renal injury caused by OTA exposure, and provide theoretical support for ASX’s role in other mycotoxin-induced damage.

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A comparison between the effects of ochratoxin A and aristolochic acid on the inflammation and oxidative stress in the liver and kidney of weanling piglets

Marin

Pistol

Gras

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

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Ochratoxin A (OTA) and aristolochic acid (AA) are toxins that can frequently contaminate cereals and cereals-based products. The present study has realized a comparison between the effect of OTA and AA on oxidative stress and inflammation in both the liver and kidney of pigs as major organs involved in the metabolism of xenobiotics. Fifteen pigs (five pigs/group) were randomly distributed in three groups (control, OTA, and AA) and were fed diets contaminated or not with 250 μg toxin/kg for 28 days. Consumption of a diet contaminated with OTA and AA increase the concentration of serum creatinine as compared with the control group. The exposure of piglets to AA decrease the activity of enzymes involved in the oxidative stress response: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxydase (GPx) in the liver and kidney while OTA decrease only GPx activity and only in the kidney. The consumption of the diets contaminated with AA increase in the liver the synthesis of tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, Interleukin (IL)-1 beta, IL-6, and IL-8 synthesis, while IL-4 was increase by OTA and decreased by AA. In the kidney, AA increase the TNF alpha and IFN gamma synthesis as compared with the control. In conclusion, our results have shown that beside the alteration of serum markers, much known indicators for nephropathy, OTA and AA can induce inflammation and oxidative stress. In conclusion, the inflammatory effects were more pronounced for AA and at the liver level, while oxidative stress was induced both in the liver and kidney.

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Nephropathy and hepatopathy in weaned piglets provoked by natural ochratoxin A and involved mechanisms

Cited by 30 publications

References 57 publications

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

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

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

A comparison between the effects of ochratoxin A and aristolochic acid on the inflammation and oxidative stress in the liver and kidney of weanling piglets

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