Ochratoxin A Group Research Articles

Effects of embryo injected with ochratoxin A on growth performance, jejunal morphology and barrier of ducklings

ABSTRACT 1. This trial investigated the effect on embryo injected with ochratoxin A (OTA) and the growth performance, jejunal morphology and barrier of ducklings to 21 d old. 2. Two hundred forty, fertilised eggs were individually weighed and randomly assigned to two groups, a control (CON) and the OTA treatment, according to average egg weight. On d 13 of embryonic development, the treatment group was injected with 8 ng OTA/g egg and the CON group was injected with NaHCO3 solution as a placebo. All newly hatched ducklings were assigned to the CON or OTA group based on the different treatments. Each treatment consisted of six replicates and each included 10 ducklings and the experiment lasted until 21 d of age. 3. The results showed that embryos injected with OTA affected the 21 d body weight (BW) and average daily gain (ADG) of ducklings (p < 0.05). OTA exposure increased the relative weights of the liver, pancreas, gizzard, proventriculus and jejunum (p < 0.05); and decreased the relative length of the jejunum of ducklings (p < 0.05). Moreover, jejunal crypt depth increased (p < 0.05) and the villus height-to-crypt depth ratio (Vh/Cd) decreased in the OTA-injected group (p < 0.05). Compared with those in the CON group, the mRNA expression of Zonula Occludens-1; (ZO-1) (p = 0.0582) and Occludin; (p = 0.0687) in the OTA treatment group was downregulated. 4. The findings demonstrated that a single low-dose injection of OTA increased body weight and daily gain in ducklings. Moreover, embryo exposure to OTA had negative effects with increased relative weight of organs and the jejunal crypt depth, decreased relative length of the intestine and mRNA expression of tight junctions (ZO-1, Occludin).

Protective Effects of a Red Orange and Lemon Extract (RLE) on the Hepatotoxicity Induced by Ochratoxin A in Rats.

Ochratoxin A (OTA) is a highly potent mycotoxin that contaminates many kinds of food and feed sources. Its significant impact on human health and animal productivity makes it a topic of particular concern. The role of specific bioactive compounds used as dietary antioxidants is believed to be substantial due to their capacity to act as free radical scavengers. Because of the well-known oxidative stress induced by OTA, the primary objective of this work was to evaluate the antioxidant effects of a standardized powder extract recovered from citrus processing waste, red orange and lemon extract (RLE), on liver damage induced by OTA in a rat model. This study aimed to examine the impact of oral administration of RLE (90 mg/kg b.w.) on hepatic function and oxidative balance in Sprague-Dawley rats (n = 6/group) treated with OTA (0.5 mg/kg b.w.) over a period of 14 days. The administration of OTA alone resulted in both biochemical changes and an imbalance in redox status in the liver. However, the use of RLE alleviated the activity of antioxidant enzymes and dramatically decreased the serum levels of ALT (alanine aminotransferase), AST (aspartate aminotransferase), and ALP (alkaline phosphatase), providing evidence of its protective benefits. Based on the findings from liver histology tests, the administration of RLE resulted in mitigation of lymphoplasmacytic inflammation, steatosis, and necrosis in the OTA group. These results indicate that the novel phytoextract RLE holds potential for application in the field of nutraceuticals.

Selenomethionine attenuates ochratoxin A-induced small intestinal injury in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation

The aim of this study was to investigate whether selenomethionine (SeMet) could attenuate intestinal injury in rabbits induced by ochratoxin A (OTA). Sixty 35-day-old IRA rabbits with similar weights were randomly assigned to the control group, OTA group (0.2 mg OTA/kg b.w), OTA+ 0.2 mg/kg Se (0.2 mg OTA/kg b.w + 0.2 mg SeMet/kg feed), OTA+ 0.4 mg/kg Se (0.2 mg OTA/kg b.w + 0.4 mg SeMet/kg feed) and OTA+ 0.6 mg/kg Se (0.2 mg OTA/kg b.w + 0.6 mg SeMet/kg feed). The rabbits were examined after oral administration of different doses of SeMet for 21 days and were intragastrically administered OTA for 7 consecutive days. The results showed that pretreatment with different doses of SeMet protected against the changes in serum biochemical indicators and the decline in production performance caused by OTA exposure. In addition, the activities of SOD, GSH-PX and T-AOC were significantly increased, and the levels of MDA and ROS were decreased after SeMet pretreatment; thus, oxidative damage in rabbit jejunum tissue due to OTA exposure was inhibited. SeMet stimulates Nrf2 and inhibits the NF-κB signalling pathway; the anti-inflammatory response and antioxidative stress in rabbits were improved, and the intestinal barrier damage caused by OTA exposure was improved. In summary, SeMet alleviates OTA-induced intestinal toxicity in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation. Moreover, 0.4 mg/kg SeMet induced the most significant improvement.

Enzymatic degradation of ochratoxin A in the gastrointestinal tract of piglets.

Animal feeds are often contaminated with ochratoxin A (OTA), a potent natural mycotoxin hazardous to animal and human health that accumulates in blood and tissues. To the best of our knowledge, this study is the first to investigate the in vivo application of an enzyme (OTA amidohydrolase; OAH) that degrades OTA into the nontoxic molecules phenylalanine and ochratoxin α (OTα) in the gastrointestinal tract (GIT) of pigs. Piglets were fed six experimental diets over 14 days, varying in OTA contamination level (50 or 500 μg/kg; OTA50 and OTA500) and presence of OAH; a negative control diet (no OTA added) and a diet containing OTα at 318 µg/kg (OTα318). The absorption of OTA and OTα into the systemic circulation (plasma and dried blood spots, DBS), their accumulation in kidney, liver, and muscle tissues, and excretion through feces and urine were assessed. The efficiency of OTA degradation in the digesta content of the GIT was also estimated. At the end of the trial, accumulation of OTA in blood was significantly higher in OTA groups (OTA50 and OTA500) in comparison to enzyme groups (OAH50 and OAH500, respectively). The supplementation of OAH explicitly reduced the absorption of OTA (P < 0.005) into plasma by 54% and 59% (from 40.53 ± 3.53 to 18.66 ± 2.28 ng/mL in piglets fed the 50 μg OTA/kg diets and from 413.50 ± 71.88 to 168.35 ± 41.02 ng/mL in piglets fed the 500 μg OTA/kg diets, respectively) and in DBS by 50% and 53% (from 22.79 ± 2.63 to 10.67 ± 1.93 ng/mL in piglets fed the 50 μg OTA/kg diets and from 232.85 ± 35.16 to 105.71 ± 24.18 ng/mL in piglets fed the 500 μg OTA/kg diets, respectively). The OTA concentrations in plasma were positively associated with the OTA levels detected in all tissues analyzed; adding OAH reduced OTA levels in the kidney, liver, and muscle (P < 0.005) by 52%, 67%, and 59%, respectively. The analysis of GIT digesta content showed that OAH supplementation led to OTA degradation in the proximal GIT where natural hydrolysis is inefficient. Overall, the data of present in vivo study demonstrated that supplementation of swine feeds with OAH successfully reduced OTA levels in blood (plasma and DBS) as well as in kidney, liver, and muscle tissues. Therefore, an approach to use enzymes as feed additives might be most promising to mitigate the harmful effects of OTA on the productivity and welfare of pigs and at the same time improving the safety of pig-derived food products.

Acute intoxication with single oral dose of ochratoxin A (OTA) causes leukopenia, heteropenia, lymphopenia and lymphoid depletion in the bursa of Fabricius in broiler chicks

Ochratoxin A (OTA) is a mycotoxin produced by species of Penicillium and Aspergillus, agricultural product contaminants. Chronic and sub-chronic OTA intoxication by chickens ingesting contaminated feed, leads to health damages due to its hepatotoxic, nephrotoxic, cytotoxic, immunotoxic, gastrotoxic, and possibly carcinogenic effects. As there are few data on acute intoxication, the present study evaluated the effects of a single acute OTA intoxication dose on immunological and hematological parameters in chicks. Sixteen one-day-old chicks were used, separated into two groups (n=8). A single dose of OTA (1400 µg kg-1 body weight) was administered, via gavage, for the OTA group and one dose of sterile PBS for the control group. On the 13th day, blood samples were collected to assess hematological and biochemical parameters, and on the 14th day, euthanasia and collection of lymphoid organs were performed. The animals of the OTA group demonstrated a significant decrease in total circulating leukocytes (p&lt;0.001) with heteropenia (p&lt;0.001) and lymphopenia (p=0.023), decrease hematocrit (p=0.020), hemoglobin (p=0.032), and plasma IgA (p =0.044), and increased plasma uric acid level (p=0.045), in relation to the control group. In addition, the animals intoxicated with OTA showed depletion of lymphoid cells in the bursa of Fabricius (p=0.016), but not in the thymus or spleen (p&gt;0.05), compared to the control. For the other parameters: total plasma proteins, plasma IgY levels, and anti-Newcastle Disease Virus (NDV) vaccine titers from matrices, there were no significant differences between the analyzed groups (p&gt;0.05), although there was a worsening tendency in contaminated animals. In conclusion, even a single acute OTA intoxication at a high dose, leads to the suppression of the systemic immune response, also affecting some hematological or biochemical parameters in chicks.

Protective Effect of SeMet on Liver Injury Induced by Ochratoxin A in Rabbits.

Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced liver injury in rabbits. Sixty 35-day-old rabbits with similar body weight were randomly divided into five groups: control group, OTA group (0.2 mg/kg OTA), OTA + 0.2 mg/kg SeMet group, OTA + 0.4 mg/kg SeMet group and OTA + 0.6 mg/kg SeMet group. Rabbits were fed different doses of the SeMet diet for 21 d, and OTA was administered for one week from day 15 (the control group was provided the same dose of NaHCO3 solution). The results showed that 0.4 mg/kg SeMet could significantly improve the liver injury induced by OTA poisoning. SeMet supplementation can improve the changes in physiological blood indexes caused by OTA poisoning in rabbits and alleviate pathological damage to the rabbit liver. SeMet also increased the activities of SOD, GSH-Px and T-AOC and significantly decreased the contents of ROS, MDA, IL-1β, IL-6 and TNF-α, effectively alleviating the oxidative stress and inflammatory response caused by OTA poisoning. In addition, OTA poisoning inhibits Nrf2 and HO-1 levels, ultimately leading to peroxide reaction, while SeMet activates the Nrf2 signaling pathway and enhances the expression of the HO-1 downstream Nrf2 gene. These results suggest that Se protects the liver from OTA-induced hepatotoxicity by regulating Nrf2/HO-1 expression.

A Newly Isolated Alcaligenes faecalis ANSA176 with the Capability of Alleviating Immune Injury and Inflammation through Efficiently Degrading Ochratoxin A.

Ochratoxin A (OTA) is one of the most prevalent mycotoxins that threatens food and feed safety. Biodegradation of OTA has gained much attention. In this study, an Alcaligenes faecalis strain named ANSA176, with a strong OTA-detoxifying ability, was isolated from donkey intestinal chyme and characterized. The strain ANSA176 could degrade 97.43% of 1 mg/mL OTA into OTα within 12 h, at 37 °C. The optimal levels for bacterial growth were 22–37 °C and pH 6.0–9.0. The effects of ANSA176 on laying hens with an OTA-contaminated diet were further investigated. A total of 36 laying hens were assigned to three dietary treatments: control group, OTA (250 µg/kg) group, and OTA + ANSA176 (6.2 × 108 CFU/kg diet) group. The results showed that OTA decreased the average daily feed intake (ADFI) and egg weight (EW); meanwhile, it increased serum alanine aminopeptidase (AAP), leucine aminopeptidase (LAP), β2-microglobulin (β2-MG), immunoglobulin G (IgG), tumor necrosis factor-α (TNF-α), and glutathione reductase (GR). However, the ANSA176 supplementation inhibited or attenuated the OTA-induced damages. Taken together, OTA-degrading strain A. faecalis ANSA176 was able to alleviate the immune injury and inflammation induced by OTA.

Metabolomics analysis underlay mechanisms in the renal impairment of mice caused by combination of aflatoxin M1 and ochratoxin A

Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are pernicious mycotoxins widely co-existing in the environment. However, nephrotoxicity and underlying mechanism induced by AFM1 coupled with OTA still remain to be explored. In this study, CD-1 mice were treated with 3.5 mg/kg b.w. AFM1, OTA, and AFM1 + OTA for 35 days, and UPLC-MS-based metabolomics method was effectuated to investigate metabolomic profiles of mice kidney. Subsequent experiments on human renal proximal tubular (HK-2) cells were performed to dig out the causal connections between distinguished differential metabolites and nephrotoxicity. Compared with DMSO vehicle group, all three toxin treatments (AFM1 and OTA alone, and in combination) significantly reduced final body weight, and remarkably elevated the concentration of serum creatinine (SCr) and caused abnormal histological phenotypes (shown by histopathological slices). OTA, AFM1 + OTA but not AFM1 reduced the relative weight index of kidney. These phenotypic results indicated that AFM1 and OTA were both toxic to the body, and it seemed that OTA exhibited a notable impairment to kidney while AFM1 had similar but limited effect compared with OTA. Further metabolomics analysis showed that when AFM1 and OTA were combined together, OTA exerted dominant effect on the alteration of metabolic processes. There were few differences in the number of changed metabolites between OTA and AFM1 + OTA group. Among the differentially expressed metabolites affected by OTA, and AFM1 + OTA, lysophosphatidylcholines (LysoPCs) were identified as the main type with significant upregulation, in which LysoPC (16:0) accounted for the most prime proportion. Western blotting results of HK-2 cells showed that single OTA and AFM1 + OTA increased the apoptotic protein expressions of Bax, caspase 3 and PARP, and decreased the expression of Bcl-2; while AFM1 only raised the expression of caspase 3. LysoPC (16:0) but not LysoPC (18:1) lifted the protein level of caspase 3 and PARP in HK-2 cells, and reduced the level of Bcl-2. Taken together, this study is the first effort trying to assess nephrotoxicity of AFM1 with OTA, and we guessed that OTA had a more pronounced toxicity to kidney in contrast to AFM1. No obvious synergism between AFM1 and OTA was found to contribute to the occurrence or development of nephropathy. LysoPC (16:0) might be the pivotal metabolite in response to single OTA and combined AFM1 + OTA engendering renal injury.

Oral Sub-chronic Ochratoxin A Exposure Induces Gut Microbiota Alterations in Mice.

Gut microbiota plays crucial roles in maintaining host health. External factors, such as diet, medicines, and environmental toxins, influence the composition of gut microbiota. Ochratoxin A (OTA) is one of the most prevalent and relevant mycotoxins and is a highly abundant food and animal feed contaminant. In the present study, we aimed to investigate OTA gut microbiome toxicity in mice sub-chronically exposed to low doses of OTA (0.21, 0.5, and 1.5 mg/kg body weight) by daily oral gavage for 28 days. Fecal microbiota from control and OTA-treated mice was analyzed using 16S ribosomal RNA (rRNA) gene sequencing followed by metagenomics. OTA exposure caused marked changes in gut microbial community structure, including the decrease in the diversity of fecal microbiota and the relative abundance of Firmicutes, as well as the increase in the relative abundance of Bacteroidetes at the phylum level. At the family level, six bacterial families (unclassified Bacteroidales, Porphyromonadaceae, unclassified Cyanobacteria, Streptococcaceae, Enterobacteriaceae, Ruminococcaceae) were significantly altered by OTA exposure. Interestingly, OTA-induced changes were observed in the lower-dose OTA groups, while high-dose OTA group microbiota was similar to control group. Our results demonstrated that sub-chronic exposure at low doses of OTA alters the structure and diversity of the gut microbial community.

Antioxidative Effects of Curcumin on the Hepatotoxicity Induced by Ochratoxin A in Rats.

Ochratoxin A (OTA) is a powerful mycotoxin found in various foods and feedstuff, responsible for subchronic and chronic toxicity, such as nephrotoxicity, hepatotoxicity, teratogenicity, and immunotoxicity to both humans and several animal species. The severity of the liver damage caused depends on both dose and duration of exposure. Several studies have suggested that oxidative stress might contribute to increasing the hepatotoxicity of OTA, and several antioxidants, including curcumin (CURC), have been tested to counteract the toxic hepatic action of OTA in various classes of animals. Therefore, the present study was designed to evaluate the protective effect of CURC, a bioactive compound with different therapeutic properties on hepatic injuries caused by OTA in rat animal models. CURC effects were examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. At the end of the experiment, rats treated with OTA showed alterations in biochemical parameters and oxidative stress in the liver. CURC dosing significantly attenuated oxidative stress and lipid peroxidation versus the OTA group. Furthermore, liver histological tests showed that CURC reduced the multifocal lymphoplasmacellular hepatitis, the periportal fibrosis, and the necrosis observed in the OTA group. This study provides evidence that CURC can preserve OTA-induced oxidative damage in the liver of rats.

Astaxanthin Alleviates Ochratoxin A-Induced Cecum Injury and Inflammation in Mice by Regulating the Diversity of Cecal Microbiota and TLR4/MyD88/NF-κB Signaling Pathway.

Ochratoxin A (OTA) is a common environmental pollutant found in a variety of foods and grains, and excessive OTA consumption causes serious global health effects on animals and humans. Astaxanthin (AST) is a natural carotenoid that has anti-inflammatory, antiapoptotic, immunomodulatory, antitumor, antidiabetes, and other biological activities. The present study is aimed at investigating the effects of AST on OTA-induced cecum injury and its mechanism of action. Eighty C57 mice were randomly divided into four groups, including the control group, OTA group (5 mg/kg body weight), AST group (100 mg/kg body weight), and AST intervention group (100 mg/kg body weight AST+5 mg/kg body weight OTA). It was found that AST decreased the endotoxin content, effectively prevented the shortening of mouse cecum villi, and increased the expression levels of tight junction (TJ) proteins, consisting of occludin, claudin-1, and zonula occludens-1 (ZO-1). AST increased the number of goblet cells, the contents of mucin-2 (MUC2), and defensins (Defa5 and β-pD2) significantly, while the expression of mucin-1 (MUC1) decreased significantly. The 16S rRNA sequencing showed that AST affected the richness and diversity of cecum flora, decreased the proportion of lactobacillus, and also decreased the contents of short-chain fatty acids (SCFAs) (acetate and butyrate). In addition, AST significantly decreased the expression of TLR4, MyD88, and p-p65, while increasing the expression of p65. Meanwhile, the expression of inflammatory factors including TNF-α and INF-γ decreased, while the expression of IL-10 increased. In conclusion, AST reduced OTA-induced cecum injury by regulating the cecum barrier function and TLR4/MyD88/NF-κB signaling pathway.

Oxidative stress, hemato-immunological, and intestinal morphometry changes induced by ochratoxin A in APRI rabbits and the protective role of probiotics.

This work studied the protective effects of Aspergillus awamori against ochratoxin A (OTA)-induced toxicity in APRI maternal line rabbits. A total number of 48 APRI line weanling rabbits (5weeks) were divided into 4 groups (12 rabbits each) and fed the basal diet, 30ppb/kg diet of OTA, 1g/kg diet of A. awamori, and a mixture of OTA and A. awamori for 8weeks. OTA reduced the final body weight and weight gain as well as the intestinal villi length and thickness, whereas increased the feed intake and feed conversion ratio. Rabbits fed diets with OTA showed significantly reduced crude protein, lipids, and fibers apparent digestibility coefficients (P < 0.05). The red blood cells and hemoglobin were significantly decreased in the OTA group comparing with the other groups (P < 0.05). The blood total protein and albumin displayed significantly lower levels by OTA than the other groups. In contrast, glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, and creatinine levels were significantly increased by OTA (P < 0.05). Phagocytic activity (PA) and phagocytic index (PI) showed significantly (P < 0.05) decreased levels in OTA-contaminated group, while rabbits fed A. awamori significantly showed the highest PA and PI levels (P < 0.05). Dietary A. awamori kept the levels of PA and PI in rabbits fed OTA significantly higher than those fed without A. awamori (P < 0.05) and not significantly different from the control group (P > 0.05). Catalase (CAT) and superoxide dismutase (SOD) displayed significantly lower levels in the OTA group, while malondialdehyde (MDA) was significantly higher than the other groups (P < 0.05). Rabbits fed OTA-contaminated diets displayed significantly lower CAT and SOD and higher MDA than rabbits fed OTA combined with A. awamori (P < 0.05). Our results indicated that dietary A. awamori ameliorated the damage in APRI rabbits fed OTA through alleviation of oxidative stress and immunity.

Effects of Curcumin on the Renal Toxicity Induced by Ochratoxin A in Rats.

Ochratoxin A (OTA) is a powerful nephrotoxin and the severity of its damage to kidneys depends on both the dose and duration of exposure. According to the scientific data currently available, the mechanism of action still is not completely clarified, but it is supposed that oxidative stress is responsible for OTA-induced nephrotoxicity. Bioactive compound use has emerged as a potential approach to reduce chronic renal failure. Therefore, curcumin (CURC), due to its therapeutic effects, has been chosen for our study to reduce the toxic renal effects induced by OTA. CURC effects are examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. The end result of the experiment finds rats treated with OTA show alterations in biochemical and oxidative stress parameters in the kidney, related to a decrease in the Glomerular Filtration Rate (GFR). Conversely, the administration of CURC attenuates oxidative stress and prevents glomerular hyperfiltration versus the OTA group. Furthermore, kidney histological tests show a reduction in glomerular and tubular damage, inflammation and tubulointerstitial fibrosis. This study shows that CURC can mitigate OTA–induced oxidative damage in the kidneys of rats.

Selenium-enriched yeast reduces caecal pathological injuries and intervenes changes of the diversity of caecal microbiota caused by Ochratoxin-A in broilers

We investigated the protective effect and mechanism of selenium-enriched yeast (SY) on caecal injury induced by ochratoxin A (OTA) in broilers. Eighty broiler chickens of 1-day-old with similar weight were randomly assigned to Control group, OTA group, SY group and OTA + SY group, and were intragastricaly administered with OTA and SY for 21 consecutive days. The results showed that SY could reduce the caecal pathological injuries and could inhibit oxidative stress caused by OTA exposure. The OTA + SY group showed a statistically significant (p < 0.01) reduction in the level of MDA, IL-1β, IL-6 and IFN-γ, whereas the levels of GSH, SOD activity and IL-10 were significantly increased (p < 0.01). By regulating TLR4/MYD88 signaling pathway, SY inhibited the expression of NF-κB, increased the expression of tight junction-related genes Claudin-1, Occludin and ZO-1, and antagonized the intestinal barrier injury caused by OTA exposure. Moreover, the microbial diversity analyses indicated that SY could intervene changes in the diversity of gut microbiota and the imbalance of gut microbiota caused by OTA. SY could relieve caecal pathological injuries, alleviate OTA-induced caecal oxidative stress and inflammatory response, increase the gut microbial diversity and protect broiler's intestinal barrier from injury.

Protective effect of curcumin on ochratoxin A–induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota

Curcumin has antioxidant functions, regulates the intestinal microbial composition, and alleviates mycotoxin toxicity. The present study aimed to explore whether curcumin could alleviate ochratoxin A (OTA)-induced liver injury via the intestinal microbiota. A total of 720 mixed-sex 1-day-old White Pekin ducklings were randomly assigned into 4 groups: CON (control group, without OTA), OTA (fed a diet with 2 mg/kg OTA), CUR (ducks fed a diet with 400 mg/kg curcumin), and OTA + CUR (2 mg/kg OTA plus 400 mg/kg curcumin). Each treatment consisted of 6 replicates and 30 ducklings per replicate. Treatment lasted for 21 D. Results were analyzed by a two-tailed Student t test between 2 groups. Our results demonstrated that OTA treatment had the highest serum low-density lipoprotein (LDL) level among 4 groups. Compared with OTA group, OTA + CUR decreased serum LDL level (P < 0.05). OTA decreased liver catalase (CAT) activity in ducks (P < 0.05), while addition of curcumin in OTA group increased liver CAT activity (P < 0.05). 16S ribosomal RNA sequencing suggested that curcumin increased the richness indices (ACE index) and diversity indices (Simpson index) compared with OTA group (P < 0.05) and recovered the OTA-induced alterations in composition of the intestinal microbiota. Curcumin supplementation relieved the decreased abundance of butyric acid producing bacteria, including blautia, butyricicoccus, and butyricimonas, induced by OTA (P < 0.05). OTA also significantly influenced the metabolism of the intestinal microbiota, such as tryptophan metabolism and glyceropholipid metabolism. Curcumin could alleviate the upregulation of oxidative stress pathways induced by OTA. OTA treatment also increased SREBP-1c expression (P < 0.05). The curcumin group had the lowest expression of FAS and PPARG mRNA (P < 0.05) and the highest expression of NRF2 and HMOX1 mRNA. These results indicated that curcumin could alleviate OTA-induced oxidative injury and lipid metabolism disruption by modulating the cecum microbiota.

FFECT OF SOME FEED-ADDITIVES ON THE GROWTH PERFORMANCE, PHYSIOLOGICAL RESPONSE AND HISTOPATHOLOGICAL CHANGES OF RABBITS SUBJECTED TO OCHRATOXIN-A FEED CONTAMINATION

This experiment aimed to evaluate the toxic influence of ochratoxin- A (OTA) feed contamination and the effectiveness of some feed-additives (Humic acids, Bio-Plus 2B, Bio-Mos) in detoxifying ochratoxicosis. Thirty five day old weaned Animal Production Research Institute (APRI) rabbits were selected and were allocated to four groups. Group 1 (control, OTA group): rabbits were fed basal diet (ochratoxin- A level: 19 μg /kg diet). Group 2: rabbits were fed a basal diet containing 0.2 % humic acid. Group 3: rabbits were fed a basal diet containing 0.4 mg/kg diet Bacillus subtilis and Bacillus licheniformis (Bio-Plus 2B). Group 4: rabbits were fed a basal diet containing 0.1% Manna oligosaccharides (Bio-Mos). The control group showed significantly reduced feed intake, daily weight gain and growth performance index. Furthermore, there was a significant increase in AST, ALT, malondialdehyde, creatinine, and urea. Moreover, Bio-Mos group revealed significantly increased serum Hemoglobin, PCV, RBCs, MCV and RBCs/ lymphocyte ratio, and significantly decreased serum SOD and CAT activities. Additionally, internal organs (liver, kidney and intestine) of groups received feed additives revealed less deteriorative change in histopathological investigations in comparison with the control group. In conclusion, supplementation of contaminated feed with ochratoxin-A by feed-additives improves feed intake and final body weight and reduces mortality rate of rabbits. In addition, it improves liver and kidney functions and reduces its pathological changes, and restores antioxidant to its normal level.Key words: rabbits; ochratoxin-A; growth performance; anti-oxidant

Effects of curcumin on performance, antioxidation, intestinal barrier and mitochondrial function in ducks fed corn contaminated with ochratoxin A

Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial activities, and has shown highly protective effects against enteropathogenic bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal pathogenic mycotoxins. The possible effect of curcumin on the alleviation of enterotoxicity induced by OTA is unknown. The effects of dietary curcumin supplementation on OTA-induced oxidative stress, intestinal barrier and mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex 1-day-old White Pekin ducklings with initial BW (43.4±0.1 g) were randomly assigned into controls (fed only the basal diet), a group fed an OTA-contaminated diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400 mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30 ducklings and treatment lasted for 21 days. There was a significant decrease in average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05); curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA group (P<0.05). Histopathological and ultrastructural examination showed clear signs of enterotoxicity caused by OTA, but these changes were largely prevented by curcumin supplementation. Curcumin decreased the concentrations of interleukin-1β, tumor necrosis factor-α and malondialdehyde, and increased the activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight junction protein 1 mRNA and protein levels, and decreased those of ρ-associated protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression of apoptosis-related genes, and downregulated mitochondrial transcription factors A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial (P<0.05). These results indicated that curcumin could protect ducks from OTA-induced impairment of intestinal barrier function and mitochondrial integrity.

Oxidative Stress of in-Ovo Ochratoxin A Administered during Chick Embryonic Development

ABSTRACT The present work was carried out to study the effect of in-ovo injection of ochratoxin A (OTA) as an oxidative stress and its consequences on hepatic and kidney functions, thyroid activity, and histological examination of brain and liver in chicken embryos and subsequently in the hatching chicks. On the 10th day of incubation, one hundred and sixty-two fertile eggs were randomly divided into two equal treatments. Control treatment, (injected by 50 µl sodium carbonate) and OTA treatment (injected by 12.5 ng OTA dissolved in 50 µl sodium carbonate). OTA treatement group significantly reduced glutathione (GSH) and significantly increased thiobarbituric acid reactive substances production (TBARS) in embryonic and hatched chicks regarding livers, spleen, bursa of Fabricius, heart, and brain as an indicator of oxidative stress. OTA injection increased TBARS and decreased GSH levels in both allantoic and amniotic fluids. On the 14th and 16th days of incubation and at the hatch, a significant lower concentration in cholesterol and higher concentrations of alanine amino transferase, aspartate amino transferase, alkaline phosphatase, gamma glutamyl transferase, acid phosphatase enzymes activities and triglycerides in the hepatic tissues of the OTA group were observed. Histological examination of OTA group of brain and liver tissues showed some degenerative changes through the experimental period. In conclusion, in-ovo OTA treated had teratogenic and embryotoxic effects.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Effect of rMnSOD on Sodium Reabsorption in Renal Proximal Tubule in Ochratoxin A-Treated Rats.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that represent toxic real threat for human beings and animal health. In this study we evaluated the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) on oxidative stress and on the alterations of fluid reabsorption in renal proximal tubule (PT) as possible causes of OTA nephrotoxicity. Finally, we have measured the concentration of O2- in the kidney through dihydroethidium assay (DHE) and nitric oxide (NO) concentration through nitrites and nitrates assay. Male Sprague Dawley rats weighing 120-150 g were treated for 14 days by gavage, as follows: Control group, 12 rats received a corresponding amount of saline solution (including 10% DMSO); rMnSOD group, 12 rats treated with rMnSOD (10 µg/kg bw); OTA group, 12 rats treated with OTA (0.5 mg/kg bw) dissolved in 10% DMSO and then scaled to required volume with corn oil; rMnSOD + OTA, 12 rats treated with rMnSOD (10 µg/kg bw) plus OTA (0.5 mg/kg bw). Our results have shown that rMnSOD restores the alteration of reabsorption in PT in rats treated with OTA plus rMnSOD, probably through the response to pressure natriuresis, where nitric oxide plays a key role. Moreover, rMnSOD prevents the nephrotoxicity induced by OTA probably restoring the balance between superoxide and NO that is most probably the cause of hypertension and renal functional alterations through the inhibition of NO synthase. In conclusion these data provide important information for understanding of mechanism of toxic action of OTA. J. Cell. Biochem. 119: 424-430, 2018. © 2017 Wiley Periodicals, Inc.