(1) Background and (2) Methods: A 14-day in vivo, multitoxic (pure mycotoxins) rat experiment was conducted with zearalenone (ZEA; 15 μg/animal/day), deoxynivalenol (DON; 30 μg/animal/day) and fumonisin B1 (FB1; 150 μg/animal/day), as individual mycotoxins, binary (FD, FZ and DZ) and ternary combinations (FDZ), via gavage in 1 mL water boluses. (3) Results: Body weight was unaffected, while liver (ZEA↑ vs. DON) and kidney weight (ZEA↑ vs. FDZ) increased. Hepatocellular membrane lipid fatty acids (FAs) referred to ceramide synthesis disturbance (C20:0, C22:0), and decreased unsaturation (C22:5 n3 and unsat. index), mainly induced by DON and to a lesser extent by ZEA. The DON-FB1 interaction was additive on C20:0 in liver lipids. In renal phospholipids, ZEA had the strongest effect on the FA profile, affecting the saturated (C18:0) and many n6 FAs; ZEA was in an antagonistic relationship with FB1 (C18:0) or DON (C18:2 n6, C20:1 n9). Hepatic oxidative stress was the most expressed in FD (reduced glutathione and glutathione peroxidase), while the nephrotoxic effect was further supported by lipid peroxidation (malondialdehyde) in the DON treatment. (4) Conclusions: In vivo study results refer to multiple mycotoxin interactions on membrane FAs, antioxidants and lipid peroxidation compounds, needing further testing.

Scarce studies have investigated the impact of fumonisin B1 (FB1) on the hepatic tissue fatty acid (FA) profile, and no study is available on piglets. A 10-day in vivo experiment was performed on seven piglets/group: control and FB1-fed animals (diet was contaminated with fungal culture: 20 mg FB1/kg diet). Independent sample t-test was carried out at p < 0.05 as the significance level. Neither growth, nor feed efficiency, was affected. The hepatic phospholipid (PL) fatty acids (FAs) were more susceptible for FB1, while triglyceride (TG) was less responsive. The impact of FB1 on hepatic PL polyunsaturated fatty acids (PUFAs) was more pronounced than on saturated fatty acids. Among all PUFAs, predominant ones in response were docosapentaenoicacid (DPA) (↓), docosahexaenoic DHA (↓) and arachidonic acids (↑). This led to a higher omega-6:omega-3 ratio, whereas a similar finding was noted in TGs. Neither total saturation (SFA) nor total monousaturation (MUFA) were affected by the FB1 administration. The liver showed an increase in malondialdehyde, as well as antioxidant capacity (reduced glutathione and glutathione peroxidase). The plasma enzymatic assessment revealed an increase in alkaline phosphatase (ALP), while alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) were not influenced. The microscopic sections provided evidence of vacuolar degeneration of the hepatocytes’ cytoplasm, but it was not severe. Furthermore, the lung edema was developed, while the kidney was not affected. In conclusion, regarding FB1-mediated hepatotoxicity in piglets, the potential effect of slight hepatotoxicity did not compromise growth performance, at least at the dose and exposure period applied.

To test the complex, acute biochemical effects of combined, naturally co‐occurring fusariotoxins, a 5‐day rat study was performed. Mycotoxin treatment was invented by intraperitoneal injection: FB1 (F): 9 µg/animal/day (approx. 30 µg/kg bw/day), DON (D): 16.5 µg/animal/day (approx. 55 µg/kg bw/day) and ZEN (Z): 12.75 µg/animal/day (approx. 42.5 µg/kg bw/day). The binary groups (FB1 and DON [FD], FB1 and ZEN [FZ] and DON and ZEN [DZ]) as well as the ternary (FB1, DON and ZEN [FDZ]) group were dosed at the same combined level as the individual mycotoxins. Body weight, feed intake and mortality were not affected by any of the treatments. FB1 and DON in combination (FD) increased the plasma aspartate aminotransferase activity synergistically (compared to the individual FB1 and DON). In the liver, both the total glutathione (GSH) and the glutathione peroxidase (GPx) activity were increased (p < 0.05) by the binary FB1 and ZEN (FZ) and the DON and ZEN (DZ) groups as well as the ternary FB1, DON and ZEA group (FDZ) compared to the control. The GSH level of the ternary group was significantly increased compared to the FB1 group, whereas the GPx activity of the ternary group was significantly increased compared to all three the individual mycotoxin groups. The Bliss independence method revealed synergism between DON and ZEN (DZ), as well as FB1 and DON (FD) on liver GPx activity. None of the toxins alone or in combination exerted strong genotoxicity on lymphocytes, neither on the gross histopathological characteristics. However, even at these low levels acute exposure of more than one of these mycotoxins (FB1, DON and ZEN) affected metabolic and detoxification changes.

The purpose of study was to investigate the effects of T-2 toxin (4.11 mg T-2 toxin and 0.45 mg HT-2 toxin kg(-1) feed) and deoxynivalenol (5.96 and 0.33 mg 15-acetyl deoxynivalenol (DON) kg(-1) feed) in 1-year-old common carp juveniles in a 4-week feeding trial. The exposure of mycotoxins resulted in increased mortality in both groups consuming mycotoxin-contaminated diet. Parameters of lipid peroxidation were not affected during the trial, and antioxidant defence also did not show response to oxidative stress; however, glutatione peroxidase activity slightly, but significantly, decreased in the T-2 toxin group. Glutathione S-transferase activity showed moderate decrease as effect of T-2 toxin, which suggests its effect on xenobiotic transformation. Reduced glutathione concentration showed moderate changes as effect of DON exposure, but T-2 toxin has no effect. Expression of phospholipid hydroperoxide glutathione peroxidase (GPx4) genes showed different response to mycotoxin exposure. T-2 toxin caused dual response in the expression of gpx4a (early and late downregulation and mid-term upregulation), but continuous upregulation was found as effect of deoxynivalenol. Expression of the other gene, gpx4b, was upregulated by both trichothecenes during the whole period. The results suggested that trichothecenes have some effect on free radical formation and antioxidant defence, but the changes depend on the duration of exposure and the dose applied, and in case of glutathione peroxidase, there was no correlation between expression of genes and enzyme activity.

No abstract

Male Wistar rats were treated intraperitoneally (i.p.) with fumonisin B1 (FB1; 0, 20, 50 and 100 mg/kg dietary dose equivalent) for 5 and 10 days (n = 24–24 in each setting) to gain dose- and time-dependent effects on antioxidant status and oxidative stress response, clinical chemical endpoints and liver, kidney and lung histopathology and lymphocyte damage (genotoxicity). FB1 decreased feed intake, body weight gain and absolute liver weight, irrespective of the toxin dose. Relative kidney weight increased in the 10-day setting. Linear dose response was found for plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol, urea and creatinine, and exposure time-dependence for plasma creatinine level. The latter was coupled with renal histopathological findings, tubular degeneration and necrosis and the detachment of tubular epithelial cells. The pronounced antioxidant response (reduced glutathione accretion, increasing glutathione peroxidase activity) referred to renal cortical response (5–10 days exposure at 50–100 ppm FB1). Hepatic alterations were moderate, referring to initial phase lipid peroxidation (exposure time dependent difference of conjugated diene and triene concentrations), and slight functional disturbance (↑ total cholesterol). Lymphocyte DNA damage was moderate, supporting a mild genotoxic effect of FB1.

Adult male Wistar rats were enrolled in a study to test the acute hepatic effects of 50 mg/kg fumonisin B 1 in feed for 5 days. Fumonisin B 1 depressed growth and feed intake, and absolute and relative liver weight showed a significant increase. The proportions of C17:0, C18:3 n3, C22:5 n3 and C22:6 n3 fatty acids decreased in the hepatic phospholipid fraction. All proportional decreases modified the hepatocellular membrane lipids into a more rigid state. The fatty acid profile modifications were partly compensated for by endogenous glutathione (preventing the formation of conjugated dienes and trienes as initial phase lipid peroxidation indicators), while the enzymatic antioxidant defence system (glutathione peroxidase) was unaltered. In contrast, hepatic malondialdehyde, the cytotoxic product of end-phase lipid peroxidation showed a concentration increase even after 5 days of feeding. The results indicate a rather strong and rapid hepatic effect of FB 1 , immediately impairing membrane phospholipids, even before the enzymatic antioxidant defence is activated.Key words: Fumonisin B 1 , rat, hepatocellular membrane, fatty acids, oxidative stress, antioxidants Fumonisins are cancer-inducing metabolites of Fusarium proliferatum and Fusarium verticillioides. They have a long-chain hydrocarbon unit (mimicking to a certain extent cellular sphingosine and sphinganine), which plays a determinant role in their cell-membrane-associated toxicity. From the fumonisin group, fumonisin B 1 (FB 1 ) shows strong toxic effects and has been reported to promote hepatic tumour in rats. Fumonisin B 1 , the most abundant of the numerous fumonisin analogues, was classified by the IARC as a Group 2B carcinogen (possibly carcinogenic in humans; IARC, 2002).

The effect of different weaning ages, that is, 21 (G21), 28 (G28) or 35 (G35) days, on growth and certain parameters of the digestive tract was examined in rabbits to assess the risk of early weaning attributable to the less-developed digestive system. On days 35 and 42, G35 rabbits had 10% to 14% and 10% higher BW, respectively (P , 0.05), than those weaned at days 21 and 28. In the 4th week of life, early weaned animals had 75% higher feed intake than G28 and G35 rabbits (P , 0.05). The relative weight of the liver increased by 62% between 21 and 28 days of age, and thereafter it decreased by 76% between 35 and 42 days of age (P , 0.05), with G21 rabbits having 29% higher weight compared with G35 animals on day 35 (P , 0.05). The relative weight of the whole gastrointestinal (GI) tract increased by 49% and 22% after weaning in G21 and G28 rabbits, respectively (P , 0.05). On day 28, the relative weight of the GI tract was 19% higher in G21 than in G28 rabbits, whereas on day 35 G21 and G28 animals had a 12% heavier GI tract compared with G35 rabbits (P , 0.05). Age influenced the ratio of stomach, small intestine and caecum within the GI tract; however, no effect of different weaning age was demonstrated. The pH value of the stomach and caecum decreased from 5.7 to 1.6 and from 7.1 to 6.3, respectively, whereas that of the small intestine increased from 6.8 to 8.4 (P , 0.05); the differences between groups were not statistically significant. Strictly anaerobic culturable bacteria were present in the caecum in high amounts (10 8 ), already at 14 days of age; no significant difference attributable to weaning age was demonstrable. The concentration of total volatile fatty acids (tVFA) was higher in G21 than in G28 and G35 throughout the experimental period (P , 0.05). The proportion of acetic and butyric acid within tVFA increased, whereas that of propionic acid decreased, resulting in a C 3 : C 4 ratio decreasing with age. Early weaning (G21) resulted in higher butyric acid and lower propionic acid proportions on day 28 (P , 0.05). No interaction between age and treatment was found, except in relative weight of the GI tract and caecal content. In conclusion, early weaning did not cause considerable changes in the digestive physiological parameters measured, but it resulted in 10% lower growth in rabbits.