44.5 INTERACTIVE EFFECTS OF NUTRITION AND OTHER ELEMENTS
44.5.1 Different Dietary Forms of Selenium and Comparative Effects
The form of selenium in the diet was found to play an important role in the subsequent uptake and resulting toxicity. Selenomethionine is a major form of selenium found in wheat and soybean protein and may be a major form of selenium in other plants.185,186 This form of selenium is presumably an important exposure source for wild aquatic birds since the toxic thresholds in eggs for decreased hatching success and teratogenicity from lab studies with mallards proved to be nearly identical to those derived from field studies.179 Selenomethionine becomes particularly embryotoxic and teratogenic when it exceeds 4 ppm Se in the laboratory diet of mallards. At higher concentra- tions, it becomes toxic to other stages of the mallard life cycle.
44.5.1.1 Reproductive Effects in Mallards
Findings from reproductive studies have indicated that selenium as selenomethionine is consid- erably more teratogenic and generally more embryotoxic than sodium selenite or selenocystine, due to much higher accumulation in eggs when provided in this form in the diet. When mallards were fed 10 ppm selenium as selenomethionine, 25 ppm as sodium selenite was required to produce a similar decrease of 40–44% in the total number of eggs that hatched compared to controls.187,188 Furthermore, 10 ppm Se as selenomethionine was more teratogenic than sodium selenite at 25 ppm, and resulted in an incidence of 13.1% malformations that were often multiple, whereas sodium selenite (10 and 25 ppm Se) resulted in 3.6 and 4.2% malformations. The teratogenicity of selenom- ethionine was confirmed in a second experiment in which mallards received 1, 2, 4, 8, or 16 ppm Se as selenomethionine, resulting in 0.9, 0.5, 1.4, 6.8, and 67.9% malformations, respectively.189 Selenocystine at 16 ppm in the diet did not impair reproduction or result in significant malformations.
In a subsequent reproductive study with mallards, seleno-DL-methionine and seleno-L-methionine were found to be of similar toxicity, and both forms were more toxic than selenium derived from selenized yeast, which is most likely due to the presence of less toxic forms of selenium in the yeast. 190
44.5.1.2 Survival and Growth in Mallard Ducklings
Selenium as selenomethionine resulted in generally greater oxidative stress than did selenium as selenite in the diet of mallard ducklings, as reflected by effects on hepatic glutathione metabolism and lipid peroxidation.191 These findings reflect the much greater accumulation of selenium in the liver and other organs as dietary selenomethionine than as selenite. However, both forms of selenium reduced duckling growth and survival.192 When day-old ducklings were fed 10, 20, or 40 ppm Se as seleno-DL-methionine or sodium selenite for six weeks, selenium from selenomethionine accu- mulated in a dose-dependent manner in the liver. Hepatic and plasma GSH peroxidase activity was initially elevated at 10 ppm Se as selenomethionine, whereas GSSG reductase activity was elevated at higher dietary concentrations of selenium. A decrease in the concentration of hepatic-reduced glutathione (GSH) and total hepatic thiols (SH) at 20 ppm Se in the diet was accompanied by an increase in the ratio of oxidized glutathione (GSSG) to GSH and an increase in thiobarbituric acid reactive substances (TBARS) concentration as evidence of lipid peroxidation.191 Selenium from selenite accumulated in the liver to an apparent maximum at 10 ppm in the diet, resulting in an increase in hepatic GSH and GSSG, accompanied by a small decrease in hepatic total SH. Sodium selenite resulted in increased hepatic GSSG reductase activity at 10 ppm and in plasma GSSG reductase activity at 40 ppm. A small increase in lipid peroxidation occurred at 40 ppm.
44.5.1.3 Subchronic Effects on Immune Function and Hepatotoxicity in Adult Mallards
The subchronic effects of selenomethionine and sodium selenite were compared with respect to several immunologic, hematologic, and serologic parameters in adult male mallards, using
concentrations in drinking water of 0, 0.5, or 3.5 mg/L Se as sodium selenite or 2.2 mg/L Se as selenomethionine for 12 weeks.193 A battery of in vivo and in vitro immunologic assays was performed on each bird throughout the study. The selenomethionine-treated birds displayed an impaired delayed-type hypersensitive (DTH) response to tuberculin (M. bovis), as measured by the number of positive reactions present 24 h post purified protein derivative (PPD) challenge. This group also exhibited increased serum alanine aminotransferase (ALT) and plasma GSH peroxidase activities. The selenium concentration in the liver and breast muscle was significantly elevated 4- and 14-fold, respectively, over controls. Sodium-selenite-treated birds did not display any detectable differences in immune function or selenium accumulation in tissues above that of controls. Serum ALT activity was increased in the 3.5 mg/L group, although to a lesser extent than in selenome- thionine-treated birds. Concentrations of selenium as sodium selenite did not affect the immune system, whereas low concentrations of selenomethionine (2.2 mg/L Se) appeared to suppress certain aspects of the mallard immune response.
44.5.1.4 Nutrition of Diet, Source of Selenium, and Bioavailability
Since the composition of the diet of wild ducklings may vary considerably in selenium- contaminated environments, a study was conducted to compare seleno-DL-methionine (DL, previ- ously used in many lab studies), seleno-L-methionine (L, a form found in nature), selenized yeast (Y), and selenized wheat (W).194, 195 Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms for 2 weeks (Table 44.2). All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Selenium as L at 30 ppm in the diet was the most toxic form, resulting in high mortality (64%) and impaired growth (> 50%) in survivors and the greatest increase in ratio of hepatic GSSG:GSH. Selenium as both L and DL decreased the concentrations of hepatic GSH and total thiols. Selenium as Y accumulated the least in liver (approximately 50%
of other forms) and had less effect on GSH and total thiols. In contrast, when a different and commercially based basal diet, rather than the 75% wheat diet, was provided, survival of ducklings was not affected by 30 ppm Se. Again, selenium as selenized yeast was found to be less toxic than seleno-D,L-methionine, seleno-L-methionine, or selenized wheat, as reflected by the fewer effects on growth, plasma alkaline phosphatase activity, and hepatic oxidative stress. Here, greater oxidative stress for DL and L diets was manifested by significant decreases in hepatic GSH and total SH.
This may be related, in part, to the nearly double tissue accumulation of selenium from selenom- ethionine diets than from selenized yeast.
44.5.1.5 Dietary Methionine and Protein
Since both quantity and composition of dietary protein for wild ducklings may vary in selenium- contaminated environments, several studies were conducted to examine effects of methionine and protein concentration on selenium toxicity. Findings from these studies have shown the potential for antagonistic effects of selenium, methionine, and protein on duckling survival and oxidative stress.
In one study, day-old mallard ducklings received one of the following diets containing 22%
protein: unsupplemented controls, 15 ppm Se (as selenomethionine), 60 ppm Se, methionine- supplemented controls, 15 ppm Se with methionine supplement, or 60 ppm Se with methionine supplement for 4 weeks.196 In a second concurrent experiment, the above sequence was repeated with a protein-restricted (11%) but isocaloric diet. In a third concurrent experiment, protein was increased to 44% with 0, 15, or 60 ppm Se added. With 22% protein and 60 ppm Se in the diet, duckling survival and growth were reduced, and histopathological lesions of the liver occurred.
Antagonistic interactive effects occurred between supplementary methionine and selenium includ- ing complete to partial alleviation of the following selenium effects: mortality, hepatic lesions, and altered glutathione and thiol status.
© 2003 by CRC Press LLC
Table 44.2 Interactive Effects of Nutritional Factors and Other Elements on Selenium Toxicity in Birds
Species, Age
Form of Se, Dietary
(conc., ppm) Interactive Factor
Observation
Period Effects Ref.
Mallard, duckling Compared these forms:
seleno-D,L-methionine (DL), seleno-L-methionine (L), selenium from yeast (30 ppm)
Wheat diet vs.
standard diet
Day-old through 2 weeks
With wheat diet: L was most toxic with respect to mortality, decreased growth, and increased oxidative stress
With standard diet: all forms of Se less toxic than with the wheat diet
194, 195
Mallard, duckling Seleno-D,L-methionine (15 ppm)
Dietary methionine (0.42% added)
Day-old through 4 weeks
Methionine decreased Se-related histopathological lesions and oxidative stress
196
(60 ppm) Methionine decreased Se-related mortality,
histopathological lesions, and oxidative stress Mallard, duckling Seleno-D,L-methionine
(15 ppm)
Restricted dietary protein (7 or 11% vs.
22% protein controls)
Day-old through 4 weeks
Restricted dietary protein increased Se-related toxicity with respect to growth, plasma chemistries, hepatic Se accumulation, and oxidative stress
110, 196 197
(60 ppm) Se caused complete mortality in combination with
restricted dietary protein Mallard, duckling Seleno-D,L-methionine
(15 ppm)
Excess dietary protein (44 vs. 22% protein controls)
Day-old through 4 weeks
Excess dietary protein increased Se-related toxicity with respect to growth and oxidative stress
196
(60 ppm) Excess dietary protein increased Se-related toxicity
with respect to mortality, growth, hematocrit, hemoglobin, plasma chemistries, and oxidative stress
Mallard, embryo through post-hatching (reproduction study)
Seleno-D,L-methionine (10 ppm)
Sodium arsenate (25, 100, or 400 ppm As)
Embryo through 14 days post- hatching
Sodium arsenate decreased the accumulation of Se in liver and egg, and Se-related hatching failure, and teratogenesis
198 Mallard, duckling Seleno-D,L-methionine
(15 ppm)
Sodium arsenate (200 ppm As)
Day-old through 4 weeks
Sodium arsenate decreased Se-related oxidative stress
110
(60 ppm) Sodium arsenate decreased Se-related mortality,
impaired growth, histopathological lesions, hepatic Se concentration, and oxidative stress
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Mallard, embryo through post-hatching (reproduction study)
Seleno-D,L-methionine (7 ppm)
Dietary B (boric acid) (900 ppm B)
Embryo through 14 days post hatching
No interactive effects observed 199
Mallard, duckling Seleno-D,L-methionine (15 ppm)
Dietary B (boric acid) (1000 ppm) with and without restricted dietary protein
Day-old through 4 weeks
With normal protein (22%) diet, B and Se in combination decreased liver weight and altered several plasma chemistries
With restricted protein (7%) diet, B and Se in combination increased mortality and increased hepatic Se accumulation
197
(60 ppm) With normal protein (22%) diet B and Se in
combination decreased liver weight and altered several plasma chemistries
With restricted protein (7%) diet Se alone caused complete mortality
Japanese quail, chicks Sodium selenite (5 or 8 ppm)
Methylmercury chloride (20)
23 days Se protected from Hg effects including mortality and tremors
200, 201 Japanese quail,
embryos and chicks (reproductive study)
Sodium selenite (6 or 12 ppm)
Methylmercury chloride (15)
Through hatching
Se and Hg were mutually protective from adverse reproductive effects including decreased egg productivity, hatching success, and teratogenesis
202
Mallard, adult Seleno-D,L-methionine (10 ppm)
Dietary methylmercury (10 ppm Hg)
10 weeks Se protected from Hg effects including mortality, paralysis of the legs, and oxidative stress
203, 204
Mallard, embryo (reproductive study)
Seleno-D,L-methionine (10 ppm)
Dietary methylmercury (10 ppm Hg)
Embryo through 7 days post hatching
Combined Se and Hg was more toxic than either alone with respect to teratogenesis and duckling production
203
With 11% protein, selenium toxicity was greater than with 22% protein; growth of controls was less than that with 22% protein, selenium (60 ppm) caused 100% mortality, and methionine supplementation, although protective, afforded less protection than it did with 22% protein. Two other studies also reported similar interactive effects between selenium and restricted dietary protein (7%) including mortality, impaired growth, and hepatic oxidative stress.110,197
With 44% protein in the diet, ducklings experienced oxidative and renal stress, and selenium was more toxic than with methionine-supplemented diets containing 22% protein.