Effect on hepatonephric organs, serum metabolites and oxidative stress in post-weaning piglets fed purified zearalenone-contaminated diets with or without Calibrin-Z.

The objectives of this study were to investigate the toxicity of zearalenone (ZEA) on hepatonephric organs, serum metabolites and oxidative stress of piglets and to evaluate the efficacy of Calibrin-Z (CAZ) in preventing ZEA-induced adverse effects. The experiment was conducted for 22 days using 36 piglets weaned at 21 days of age (Landrace × Yorkshire × Duroc, 18 females and 18 males; 8.84 ± 0.21 kg average body weight). Piglets of each gender were randomly allocated to the following six dietary treatments: (i) Control (basal diet only); (ii) Control + 1 g/kg CAZ; (iii) Control + 1 mg/kg ZEA; (iv) Control + 1 mg/kg ZEA + 1 g/kg CAZ; (v) Control + 1 mg/kg ZEA + 2 g/kg CAZ; (vi) Control + 1 mg/kg ZEA + 4 g/kg CAZ. Piglets were housed and fed individually for the entire experimental period. Blood samples were taken, and piglets were killed at the end of the experiment to obtain organs for physiological assessment. Results showed that piglets fed the ZEA-contaminated diet had increased (p < 0.05) activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase (GGT), creatine kinase and cholinesterase, concentrations of urea, and creatinine in serum, and malondialdehyde (MDA) in serum and liver. Pigs fed the ZEA-only diet also showed reductions in serum (p < 0.05) globulin, triglycerides and high-density lipoproteins (HDL), and reductions in total superoxide dismutase (TSOD) and glutathione peroxidase (GSHPx) activity in both serum and liver. Supplementation of CAZ at the dosages of 1-4 g/kg to the diet containing 1.05 mg/kg ZEA linearly increased (p < 0.05) concentrations of triglycerides and HDL in serum, activity of TSOD and GSHPx in serum and liver, but linearly reduced (p < 0.05) all tested serum enzymes and lowered (p < 0.05) the elevated concentrations of urea, and creatinine in serum, and MDA in serum and liver caused by dietary ZEA. Piglets fed the ZEA-contaminated diet showed increased (p < 0.05) relative weight of liver and kidney compared with the control, whereas only numerical improvement on relative weight of liver and kidney was observed with simultaneous addition of CAZ at 4 g/kg diet and ZEA. However, feeding the diet with CAZ alone at 1 g/kg had no impact on any of the measured parameters when compared to the control. It is suggested that feeding ZEA at 1.05 mg/kg exerted a deleterious effect on piglets, which was totally or partly ameliorated by dietary supplementation of CAZ at concentrations between 1 and 4 g/kg diet.

Effects of purified zearalenone on growth performance, organ size, serum metabolites, and oxidative stress in postweaning gilts.

Zearalenone (ZEA), an estrogenic mycotoxin, is produced mainly by Fusarium fungi. Previous studies indicated that acute ZEA exposure induced oxidative stress and damage in multiple organs. Therefore, the present study was designed to investigate the adverse effects of dietary ZEA (1.1 to 3.2 mg/kg of diet) on oxidative stress and organ damage in postweaning gilts. A total of 20 gilts (Landrace × Yorkshire × Duroc) weaned at d 21 with an average BW of 10.36 ± 1.21 kg was used in the study. Gilts were housed in a temperature-controlled room, divided into 4 treatments, and fed a basal diet only (control) or basal diet supplemented with purified ZEA at a dietary concentration of 1 (ZEA1), 2 (ZEA2), or 3 (ZEA3) mg/kg of diet for 18 d ad libitum. The actual ZEA contents (analyzed) were 0, 1.1 ± 0.02, 2.0 ± 0.01, and 3.2 ± 0.02 mg/kg for control, ZEA1, ZEA2, and ZEA3, respectively. Gilts fed different amounts of dietary ZEA grew similarly with no difference (P > 0.05) in feed intake. Vulva size increased linearly over the 18 d of feeding in gilts fed diets containing 1.1 mg of ZEA/kg or greater (P < 0.001). Relative weight of genital organs, liver, and kidney increased linearly (P < 0.05) in a ZEA-dose-dependent manner. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamate transferase, urea, and creatinine (P < 0.05), and malondialdehyde concentrations in both serum and liver (P < 0.001) were also increased linearly in a ZEA-dose-dependent manner. However, spleen relative weight (P = 0.002) and activities of total superoxide dismutase and glutathione peroxidase (in both serum and liver (P < 0.05) were decreased linearly as dietary ZEA increased. Results showed that besides genital organs, the liver, kidney, and spleen may also be target tissues in young gilts fed diets containing 1.1 to 3.2 mg of ZEA/kg for 18 d. Increased key liver enzymes in the serum suggest progressive liver damage caused by feeding ZEA, and an increase in oxidative stress in gilts is another potential impact of ZEA toxicity in pigs.

Effects of low phytate barley (Hordeum vulgare L.) on zinc utilization in young broiler chicks.

Two 21-d experiments were conducted to evaluate the effects of low phytate barley (LPB) on Zn utilization by young broiler chicks and to determine the contribution of endogenous phytase, present in LPB. In the first experiment, ninety-six 1-d-old male chicks were assigned to a 2 x 3 factorial arrangement of treatments (4 pens of 4 chicks/treatment). Factors were barley type [wild-type barley (WTB) and LPB mutant M 955] and supplemental Zn (0, 10, or 20 mg of Zn/kg). In the second experiment, two hundred forty 1-d-old straight-run broiler chicks were assigned to a 2 x 2 x 3 factorial arrangement of treatments (4 pens of 5 chicks/treatment). Factors were barley type (WTB and LPB), autoclave treatment [nonautoclaved or autoclaved (121 degrees C, 20 kg/cm(2), 20 min)], and supplemental Zn (0, 10 or 20 mg of Zn/kg). Barley made up 60% of the diets and was the only source of phytate. On average, basal diets contained 26 mg of Zn/kg. Feed intake and body weight gain were greater (P < 0.05) in broilers fed LPB compared with WTB in experiment 2. Zinc concentration in toes and tibias were affected (P < 0.0001) by barley type (LPB > WTB) and supplemented Zn levels (20 > 10 > 0 mg of Zn/kg), and significant barley type x Zn interactions were also observed in both experiments. Substitution of LPB for WTB increased tibia and toe Zn by 46 and 25%, respectively, an increase comparable to that achieved with supplementing the diet with 20 mg of Zn/kg. No effect of autoclaving was observed for any variable in experiment 2. Retention of P and Zn was higher (P < 0.001) in chicks fed LPB compared with WTB in both experiments. Zinc retention was influenced (P < 0.0001) by dietary Zn, and barley type x Zn level interactions (P < 0.05) were observed in both experiments. Chicks fed LPB utilized more dietary Zn and P than those fed WTB, and this improved mineral utilization was not due to endogenous phytase present in barley.

Individual and combined effects of the Fusarium mycotoxins fumonisin B1 and moniliformin in broiler chicks.

The individual and combined effects of feeding fumonisin B1 (FB1; 0, 100, 200 mg FB1/kg) and moniliformin (M; 0, 100, 200 mg M/kg) were evaluated using a 3 x 3 factorial arrangement of treatments. Significant mortality (P < 0.05) occurred in chicks fed all diets containing 200 mg M/kg (50%-65%). Compared with controls and chicks fed FB1, both feed intake and body weight gain were decreased (P < 0.05) in chicks fed diets containing 100 mg M/kg. Chicks fed M had heavier heart weights (P < 0.05) than control chicks or chicks fed FB1. Compared with controls, chicks fed diets containing 200 mg M/kg or a combination of 200 mg FB1/kg and 100 mg M/kg had increased kidney and liver weights (P < 0.05). Significant FB1 by M interactions (P < 0.05) were observed for serum total protein and aspartate aminotransferase. Mild to moderate periportal extramedullary hematopoiesis and mild focal hepatic necrosis were observed in chicks fed FB1 alone. An increased incidence of large pleomorphic cardiomyocyte nuclei, loss of cardiomyocytes, and mild focal renal tubular mineralization were observed in chicks fed M alone. Both cardiac and renal lesions were observed in chicks fed combinations of FB1 and M. Data indicate FB1 and M, alone or in combination, can adversely affect chick performance and health at these dietary concentrations. The interactive effects of FB1 and M were not synergistic and were less than additive in nature. At the dietary concentrations studied, M is much more toxic to broilers than FB1.

Chronic effects of moniliformin in broiler and turkeys fed dietary treatments to market age.

Floor pen studies were conducted, with broilers from 1 to 7 wk of age and with turkeys from 1 to 14 wk of age, to evaluate the chronic effects of moniliformin (M). Fusarium fujikuroi (M-1214) culture material was added to typical corn-soybean basal diets to supply 0, 25, or 50 mg M/kg diet (broilers) or 0, 12.5, 25, 37.5, or 50 mg M/kg diet (turkeys). Compared with controls, chicks fed diets containing 50 mg M/kg consumed more feed, had lower body weight gain, were less efficient in converting feed to body weight gain, and had increased relative heart and proventriculus weights. Chicks fed the diet containing 50 mg M/kg also had significantly higher mortality and decreased mean corpuscular volumes compared with controls. Broilers fed 25 and 50 mg M/kg also had increased serum gamma glutamyltransferase activities. Feed intake, body weight gain, and feed conversion of turkeys fed dietary M were not affected. At 6 and 14 wk, turkeys fed 25, 37.5, or 50 mg M/kg diet had increased (P < 0.05) relative heart weights when compared with controls. At week 14, turkeys fed diets containing 37.5 or 50 mg M/kg also had increased (P < 0.05) relative liver weights compared with turkeys fed 0, 12.5, or 25 mg M/kg diet. Lesions, observed only in the hearts of broilers and turkeys fed 50 mg M/kg, were loss of cardiomyocyte cross striations, increased cardiomyocyte nuclear size, and an increased number of cardiomyocyte mitotic figures (turkeys only). Results indicate that > or = 37.5 mg M/kg is hepatoxic and > or = 25 mg M/kg is cardiotoxic to turkeys and 50 mg M/kg diet is toxic to broilers fed to market age.

Chronic effects of fumonisin B1 in broilers and turkeys fed dietary treatments to market age.

Floor pen studies were conducted with 270 broiler chicks and 144 turkey poults, all 1 wk old, to evaluate the chronic effects of fumonisin B1 (FB1). A completely randomized design was used in both studies with six pen replicates of 15 chicks or eight pen replicates of six poults assigned to each of three dietary treatments from Weeks 1 to 7 (broilers) or to Week 14 (turkeys). Fusarium moniliforme (M-1325) culture material was added to a typical corn-soybean basal diet to supply 0, 25, or 50 mg FB1/kg diet. Feed intake, body weight gain, and feed conversion of chicks were not affected (P > 0.05) by FB1. Turkeys fed 50 mg FB1/kg had significantly (P < 0.05) lower feed intake than the controls. Compared with controls, chicks and turkeys fed FB1 diets had significantly higher liver sphinganine to sphingosine ratios (P < 0.05). Relative organ weights of chicks were not affected (P > 0.05) by FB1, other than those chicks fed 25 mg FB1/kg, which had lower (P < 0.05) relative proventriculus weights than the chicks fed 0 or 50 mg FB1/kg. Broilers fed 50 mg FB1/kg had decreased serum calcium and increased serum chloride when compared to broilers fed 0 or 25 mg FB1/kg. Hematology was not affected (P > 0.05) by dietary FB1. No lesions were present in any organ examined microscopically. Results indicate that 50 mg FB1/kg diet is detrimental to turkeys but is not toxic to broilers fed to market age.

Effects of feeding Fusarium fujikuroi culture material, containing known levels of moniliformin, in young broiler chicks.

An experiment was conducted with 270 male broiler chicks to evaluate the effects of a Fusarium fujikuroi M-1214 culture material containing moniliformin (M) on broiler chicks. Day-old chicks were allotted randomly to dietary treatments containing 0, .24, .48, .72, .96, 1.44, 1.92, 2.40, and 2.88% M culture material (MCM). These levels of MCM supplied 0, 25, 50, 75, 100, 150, 200, 250, or 300 mg M/kg of feed. Each dietary treatment was fed to six pen replicates of five chicks per pen for 21 d. Significant mortality (P < .05) occurred in chicks fed 200 (8 out of 30), 250 (17 out of 30), and 300 (25 out of 30) mg M/kg feed. Chicks fed > 100 mg M/kg had lower (P < .05) feed intakes and smaller BW gains (P < .05) than controls. Increased heart weights (P < .05) were observed in chicks fed > 50 mg M/kg, and increased liver weights (P < .05) in chicks fed > 100 mg M/kg. Gross lesions of M toxicity included generalized cardiomegaly with dilation of the right ventricle. Histopathology revealed a high incidence of large and variably shaped cardiomyocyte nuclei and a generalized loss of cardiomyocyte cross striations in chicks fed > 75 and 200 mg M/kg, respectively. Results indicated that F. fujikuroi culture material containing M is toxic to young broiler chicks.

Dinuclear complexes of platinum having anticancer properties. DNA-binding studies and biological activity of bis(4,4'-dipyrazolylmethane-N,N')- bis[dichloroplatinum(II)] and related complexes.

Some DNA-binding experiments employing a selected number of novel dinuclear platinum complexes with the 4,4'-dipyrazolylmethane (dpzm) ligand are reported. A DNA-cleavage assay using Eco RI and Bam HI restriction endonucleases to probe the binding of the complexes at or near their unique restriction sequences of pUC9 DNA has been examined. The complex beta-[Cl2Pt(dpzm)2PtCl2] has a greater affinity for DNA at the Eco RI restriction sequence over the Bam HI site. To our knowledge, the preferential inhibition of Eco RI activity is unprecedented for any platinum species reported to date. Further, the dinuclear complexes beta-[Cl2Pt(dpzm)2PtCl2], beta-[Cl4Pt(dpzm)2PtCl4] x 0.5dmf x 0.5H2O and [Cl4Pt(dpzm)2PtCl2] are capable of inhibiting Eco RI activity to a far greater extent than the platinum anticancer drug cis-[PtCl2(NH3)2] (cisplatin). The in vivo and in vitro anticancer properties of some of the platinum complexes are also described. The complexes alpha-[Cl2Pt(dpzm)2PtCl2] x 0.5dmf and beta-[Cl2Pt(dpzm)2PtCl2] display significant activity against P388 lymphocytic leukemia in mice.

Irritancy and anti-inflammatory activity of bis(eta 5-cyclopentadienyl)titanium(IV) complexes in rats.

Dichloro-bis(eta 5-cyclopentadienyl)titanium(IV) and some related complexes were compared with cis-dichlorodiammineplatinum(II) in rats for acute anti-inflammatory activity against carrageenan paw oedema, anti-arthritic activity against developing and established adjuvant-induced polyarthritis, immunosuppressant activity in a local graft-vs. host assay, irritant effects at sites of administration (paw, skin, peritoneum) and nephro- and gastro-toxicities. These titanium complexes, like cisplatin and its hydrolysis products, in vivo exhibited both anti-inflammatory and anti-arthritic activity as well as immunosuppressant effects. Nephro- and gastro-toxicity were much less severe than in rats given platinum complexes. In vitro they selectively inhibited [3H]thymidine incorporation by isolated thymocytes and prevented the germination of radish seeds. When given intraperitoneally, the anti-inflammatory activity may partly be due to a counter-irritant phenomenon since the titanium derivatives elicited an acute peritoneal effusion if they were injected towards the omentum. However, when injected subcutaneously or applied in dimethylformamide or dimethylsulfoxide to the skin, they manifested both anti-inflammatory and anti-arthritic activity without irritancy or much local skin damage. They might therefore have the potential of being useful drugs, especially if released slowly.

cis-Platinum(II) amine complexes: some structure-activity relationships for immunosuppressive, nephrotoxic and gastrointestinal (side) effects in rats.

A local graft-versus-host reaction was established to elicit lymphoid hypertrophy in F1 hybrid PVG X Lew rats. cis-Di(amine)platinum(II) complexes were given i.p. on days 1--4 in divided doses. Overnight proteinuria and measurements of renal hypertrophy on day 5 reflected the nephrotoxicity of the test compound. Stomach weights indicated the peculiar effect on pyloric stasis causing gastric distension. Weights of thymus' and spleens together with lymph-nodes showed the lymphodepressant/immunosuppressive properties of platinum compounds. Structure activity relationships for immunosuppressant, nephrotoxic and gastric-distending activities were investigated with: (a) cis-diaquo, cis-hydroxyaquo- and cis-dichlorodi(amine)platinum(II) complexes; (b) dinuclear mu-dihydroxo-bridged di(amine)platinum(II) complexes; (c) carboxylatodi(amine)platinum(II) complexes. Nephrotoxicity was minimised (with retention of immunosuppressant activity) by (a) the use of certain N-substituted amines e.g. Dach, Me4en; (b) co-administration of selected adjuncts e.g. citrate, salicylate; (c) auxiliary treatment with a penicillin mixture (Triplopen). In vitro effects of some platinum(II) compounds on isolated rat kidney tubules were also investigated.

Platinum drugs: combined anti-lymphoproliferative and nephrotoxicity assay in rats.

A 4-day drug schedule was used to explore the efficacy and simultaneous toxicity of cisplatin and 30 other platinum (II) amines given IP to PVG x Lew F1 hybrid rats at cumulative doses of 10-300 mumol/kg. Toxic effects monitored were stomach enlargement, kidney hypertrophy with tubular necrosis and proteinuria, evident visceral mucin, and lymphoid involution (thymus, spleen). Immunosuppressive effects were monitored as inhibition of the lymph node hypertrophy induced by grafting PVG spleen cells into each paw of F1 hybrids. No significant activity/toxicity was observed with 'platinum-(pyrimidine) blues'. N-alkyl derivatives of cisplatin were less active/toxic and some had no immunosuppressant effect, though they are reported as effective antitumour agents (in mice). mu-Hydroxobridged aminoplatinum (II) dimers were highly toxic, effective immunosuppressants and their toxicity profiles were distinct from the dihalo or diaquo diaminoplatinum species. 1,2-Diaminocyclohexane platinum derivatives showed a wide range of potency, all being much less nephrotoxic than cisplatin.