A compound preparation for relieving selenium poisoning, feed and application thereof

Abstract

The present application belongs to the technical field of feed additives, and specifically provides a compound preparation for relieving selenium poisoning, which comprises taurine, vitamin E, glutathione, allicin and carotene. The compound preparation provided by the present application utilizes the synergistic effect among taurine, vitamin E, glutathione, allicin and carotene, replaces the commonly used intravenous injection of sodium thiosulfate antidote, slows down the absorption speed of selenium, relieves the oxidation of selenium to the lipid on the surface of liver cell membrane, and removes the by-products such as free radicals after selenium metabolism. By adopting sodium selenite to simulate the environment under acute high-concentration selenium exposure, it is proved that the compound preparation has certain relieving effect on the growth inhibition and liver damage caused by acute selenium poisoning.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of feed additives, and particularly relates to a compound preparation for relieving selenium poisoning, feed and application thereof. BACKGROUND

[0002] Selenium, as an essential trace element of the body, plays an important role in maintaining growth metabolism, oxidation resistance, cancer resistance, improving immunity and reproductive performance, etc. Under normal circumstances, selenium enters the body through the digestive tract, respiration, injection, etc., is then absorbed into the blood in the duodenum and caecum, and is transported to various tissues and organs for utilization. The liver is the main organ for selenium metabolism and storage, most of the selenium-containing substances are synthesized here, and selenium is methylated in the liver by methyltransferase, and is excreted out of the body through respiration and urine. In higher animals, selenium and sulfur have a competitive effect, selenium can replace the sulfhydryl group of sulfur-containing amino acids (cystine, methionine, tryptophan) enzymes and produce an inhibitory effect on the oxidation process of cell metabolism. When the body is exposed to a high-concentration selenium environment, the methylation pathway of selenium is inhibited, the body's selenium balance is disrupted, and toxicity is caused.

[0003] At present, the distribution of selenium elements in China is extremely uneven, and there are extensive selenium-deficient areas, and unknown selenium-excessive areas, such as Hubei and Shanxi. Due to the enrichment effect of the ecological system, the selenium elements in the soil of these areas are accumulated in forage grasses and crops, causing local people and livestock to be exposed to a high-concentration selenium environment for a long time, causing subacute or chronic poisoning. Selenium generally has two forms, inorganic selenium and organic selenium. Inorganic selenium generally refers to sodium selenite and sodium selenate, which are most commonly used as selenium supplements, but inorganic selenium has stronger toxicity to the body, resulting in a lower biological activity threshold. Organic selenium mainly includes selenium methionine, selenium cysteine and potassium selenocyanate, etc., and has high biological activity and bioavailability. The toxicity size is generally: sodium selenite > sodium selenate > organic selenium. As a necessary nutrient element, selenium is often added to feed, but due to uneven mixing of the additive, the local selenium content of the feed is relatively high, and the toxic threshold dose of selenium is low, which easily causes acute selenium poisoning of livestock. SUMMARY

[0004] The purpose of the present application is to solve the problem of acute selenium poisoning of livestock and poultry.

[0005] To this end, the present application provides a compound preparation for relieving selenium poisoning, which comprises taurine, vitamin E, glutathione, allicin and carotene.

[0006] Specifically, the compound preparation comprises 50-55% of taurine, 2-5% of vitamin E, 10-15% of glutathione, 25-30% of allicin and 5-15% of carotene, in terms of mass percentage.

[0007] The composting pool can be used for repairing growth performance and liver damage of selenium poisoning animals.

[0008] The application further provides a feed for relieving selenium poisoning, which comprises a basic daily ration and the compound preparation.

[0009] Specifically, the addition amount of the compound preparation is 0.5-2% based on the mass of the basic daily ration.

[0010] Compared with the prior art, the application has the following advantages and beneficial effects:

[0011] The compound preparation for relieving selenium poisoning provided by the application utilizes the synergistic effect among taurine, vitamin E, glutathione, allicin and carotene, replaces the commonly used intravenous injection of sodium thiosulfate antidote, slows down the absorption speed of selenium, relieves the oxidation of selenium on the surface lipid of hepatocyte membrane, and removes the by-products such as free radicals after selenium metabolism. By using sodium selenite to simulate the environment under acute high-concentration selenium exposure, it is proved that the compound preparation has certain relieving effect on growth inhibition and liver damage caused by acute selenium poisoning. DETAILED DESCRIPTION

[0012] The technical solutions in the application will be described clearly and completely below with reference to the embodiments. Obviously, the described embodiments are only some of the embodiments of the application, but not all the embodiments. Although the representative embodiments of the application have been described in detail, those skilled in the art will understand that various modifications and changes can be made to the application without departing from the scope of the application. Therefore, the scope of the application should not be limited to the embodiments, but should be defined by the appended claims and their equivalents.

[0013] The application provides a compound preparation for relieving selenium poisoning, which comprises taurine, vitamin E, glutathione, allicin and carotene.

[0014] Specifically, the compound preparation comprises 50-55% of taurine, 2-5% of vitamin E, 10-15% of glutathione, 25-30% of allicin and 5-15% of carotene in terms of mass percentage.

[0015] Among them, allicin is a monomer sulfur compound isolated from the bulb of Allium sativum L. of Liliaceae, the main component is diallyl disulfide, has various pharmacological properties, including anti-infection, anti-stone, anti-tumor, anti-atherosclerosis, anti-diabetes and anti-obesity, etc. 2-aminoethanesulfonic acid (Tau), also known as taurine, is a ubiquitous sulfur-containing amino acid derivative, a non-essential amino acid in the body, exists in most animal tissues, Tau has the effects of maintaining normal electron transport chain, maintaining glutathione storage, up-regulating antioxidant response, increasing membrane stability, eliminating inflammatory response, etc. The antagonism of sulfur-containing compounds in allicin and taurine to selenium slows down the absorption rate of selenium.

[0016] Vitamin E (alpha-tocopherol) is a natural antioxidant, which is the main lipid-soluble antioxidant on the cell membrane. Vitamin E can prevent the oxidation of polyunsaturated fatty acids on the membrane by blocking the peroxide radical chain reaction. It can provide a hydrogen ion in the oxygen radical reaction and be converted into a less reactive form (tocopherol radical), which is then reduced by ascorbic acid-GSH redox coupling reaction; beta-carotene is the most effective singlet oxygen scavenger in nature, which has a synergistic antioxidant effect with vitamin E and relieves the oxidation of selenium to the lipid on the surface of liver cell membrane.

[0017] Glutathione can react with hydrogen peroxide or organic peroxide to protect cells from peroxide damage, is an important free radical trapping agent, and can remove free radicals and other byproducts after selenium metabolism.

[0018] The application also provides a feed for relieving selenium poisoning, which comprises a basic daily ration and the above-mentioned compound preparation. The addition amount of the compound preparation is 0.5-2% based on the mass of the basic daily ration.

[0019] The effects of the compound preparation for relieving selenium poisoning and the feed are studied through specific examples as follows.

[0020] Example 1

[0021] The example provides a compound preparation for relieving selenium poisoning, which comprises 50% taurine, 5% vitamin E, 10% glutathione, 25% allicin and 10% carotene in mass percentage. All components are in powder form.

[0022] Example 2

[0023] The example studies the relieving effect of the compound preparation on selenium poisoning of broilers by constructing a selenium poisoning model of broilers.

[0024] Test 1, determination of the lethal dose range and group interval of sodium selenite to broilers

[0025] 1. Materials and Methods

[0026] 1.1 Test materials

[0027] Test animals: 50 AA white-feathered broilers of 22 days old, half male and half female.

[0028] Sodium selenite: 98%, relative molecular mass 172.94.

[0029] 1.2 Test method

[0030] Table 1 Test design

[0031]

[0032] Select 50 healthy, well-grown AA white-feathered broilers of 22 days old, and weigh after 8 hours of feed deprivation. Divide into 10 replicates of 10 birds each, half male and half female, according to body weight approximation. After caging, administer the test substance by single oral gavage. Sodium selenite is administered by single oral gavage at 4.16, 10.00, 21.50, 46.40, and 100.00 mg / kg, calculated as Se (sodium selenite is dissolved in 0.75% saline at the corresponding weight per group total weight), 2 mL per bird. Observe for 7 days after gavage, and allow free access to feed and water during the test period.

[0033] 2. Test results and analysis

[0034] Table 2 Number of surviving birds after 7 days of gavage with yeast selenium

[0035]

[0036] 2.2 Dose range of sodium selenite

[0037] The lowest all-cause lethal concentration of sodium selenite (calculated as Se) is 21.50 mg / kg. The lowest mortality rate is 10%, at which the concentration of sodium selenite (calculated as Se) is 4.16 mg / kg.

[0038] That is, the upper limit dose is 21.50 mg / kg, and the lower limit dose is 4.16 mg / kg.

[0039] The formal test dose group is set up in 5 groups, and the group distance r is calculated according to the formula:

[0040]

[0041] Calculation shows that the interval r between the sodium selenite formal toxicity test groups is 1.51.

[0042] Test two, determination of oral LD50 of sodium selenite in broilers

[0043] The test is to determine the LD50 of sodium selenite in broilers by oral administration based on the highest lethal range and group interval determined in Test 1. 50 and the range of confidence domain.

[0044] 1. Materials and methods

[0045] 1.1 Test materials

[0046] Test animals: 60 22-day-old AA white-feathered broilers, half male and half female.

[0047] Sodium selenite: same as Test 1.

[0048] 1.2 Test method

[0049] Select 60 healthy 22-day-old AA white-feathered broilers, weigh after 8 hours of feed deprivation, and divide them into 10 replicates according to the principle of similar body weight, half male and half female, 10 birds per replicate. After caging, administer the test substance by oral gavage once. There are 6 groups of sodium selenite (treatment group 1 to treatment group 6), each with 1 replicate, and each group is administered 2.76, 4.16, 6.27, 9.46, 14.26 mg / kg (calculated as Se) of sodium selenite by oral gavage once, and the corresponding dose of sodium selenite is dissolved in normal saline, 1.5 mL per bird. Observe continuously for 7 days after gavage, and allow free access to feed and water during the test period. The grouping is shown in the table below:

[0050] Table 3 Test design

[0051]

[0052] 1.3 Calculation method of LD50 and 95% confidence limit

[0053] This test uses the modified Karber method to calculate the LD50 of sodium selenite in broilers after 7 days of feeding: 50 and the 95% confidence limit:

[0054] logLD50 = Xm - i (∑p - 0.5)

[0055] Where:

[0056] Xm - Log of the highest concentration;

[0057] i - Log of the adjacent concentration ratio (group interval);

[0058] ∑p - Sum of the mortality rates of each group (as a decimal).

[0059] LD 50 Standard error calculation formula:

[0060]

[0061] Where:

[0062] p - mortality of a group;

[0063] q - survival rate of a group;

[0064] n - number of broilers in each concentration group.

[0065] The formula for calculating 95% confidence limit is:

[0066] log LD50 = log LD95 + 1.96 x Slog LD95

[0067] 1.4 Data processing

[0068] The experimental data were arranged and analyzed by Excel.

[0069] 2. Results and analysis

[0070] 2.1 LD50 of sodium selenite 50 and 95% confidence limit

[0071] Table 4 Number of broilers died within 7 days after gavage with different concentrations of sodium selenite (Se)

[0072]

[0073] From the data in the table, the mortality rates were 20%, 70%, 60%, 90%, 100%, and 100% after a single gavage with 2.76, 4.16, 6.27, 9.46, and 14.26 mg / kg (Se) of sodium selenite, respectively.

[0074] 1) Since the minimum full-survival concentration was still not obtained in this experiment, the LD50 was calculated by the modified Karber method. 50 .

[0075] The formula is: log LD50 = Xm - i (∑p - 0.5)

[0076] Where:

[0077] Xm = Log 47.09 = 1.6729;

[0078] i = log 1.51 = 0.1790;

[0079] ∑p = 0.2 + 0.7 + 0.6 + 0.9 + 1.0 + 1.0 = 4.4;

[0080] log LD 50 = 1.6729 - 0.1790 x (4.4 - 0.5) = 0.9748.

[0081] Looking up the antilog table, we get:

[0082] LD 50= 9.4363 mg / kg (as Se), which is equivalent to the LD 50 = 20.81 mg / kg.

[0083] LD 50 Standard error:

[0084] 2) LD 50 95% confidence limit:

[0085] LD 50 95% confidence limit = log -1 (log LD 50 ± 1.96 x Slog LD 50 ) = log -1 (0.9748 ± 1.96 x 0.04736) = log -1 (0.9748 ± 0.0928) = log -1 (0.882 - 1.0676).

[0086] From the antilog table, the 95% confidence interval is 7.6208 - 11.6305.

[0087] Under the experimental conditions, the LD 50 of sodium selenite (as Se) for 22-day-old AA broilers by oral gavage was approximately 9.44 mg / kg, with a 95% confidence interval of [7.62 - 11.63 mg / kg]. Experiment III: Effects of the compound preparation on broilers exposed to high concentrations of selenium

[0088] In this experiment, the 1 / 3 LD 50 of sodium selenite for broilers was selected as the modeling dose for acute selenium poisoning in broilers, which was 3.15 mg / kg (as Se). A 1% compound preparation was added to the basal diet to antagonize the competition between selenium and sulfur in inorganic selenium by the large amount of sulfur-containing organic matter and taurine in garlic, to weaken the damage of inorganic selenium to specific enzymes in the body, and to provide strong free radical scavenging effects by vitamin E and beta-carotene, and cell membrane antioxidant protection by glutathione.

[0089] 1. Materials and Methods

[0090] 1.1 Test materials

[0091] Test animals: 270 AA white-feathered broilers, half male and half female.

[0092] Sodium selenite: same as Experiment I.

[0093] 1.2 Test method

[0094] 270 healthy and uniform 1-day-old AA white-feathered broilers were randomly divided into 3 groups, and the broilers were raised for 21 days. The broilers were weighed at 8:00 on the 21st day, and then divided into 3 groups according to the weight, with 6 replicates in each group, and 15 broilers in each replicate. Among them:

[0095] Control group 1: fed with the basic diet;

[0096] Sodium selenite exposure group: fed with the basic diet and gavaged with 3.15 mg / kg (Se) sodium selenite on the 22nd day;

[0097] Compound preparation treatment group: fed with the basic diet + 1% compound preparation in Example 1, and gavaged with 3.15 mg / kg (Se) sodium selenite on the same day;

[0098] Control group 2: fed with the basic diet + 1% vitamin E, and gavaged with 3.15 mg / kg (Se) sodium selenite on the same day;

[0099] Control group 3: fed with the basic diet + 1% taurine, and gavaged with 3.15 mg / kg (Se) sodium selenite on the same day;

[0100] Control group 4: fed with the basic diet + 1% allicin, and gavaged with 3.15 mg / kg (Se) sodium selenite on the same day.

[0101] The sodium selenite group, compound preparation group and control groups 2-3 were weighed according to the total weight of each cage, and 3.15 mg / kg (Se) sodium selenite was dissolved in 0.75% saline, and gavaged at 1.5 mL per bird. The control group was gavaged with the same dose of saline. The test lasted for 21 days, and the broilers were allowed to freely eat and drink during the test.

[0102] 1.3 Test feed and feeding management

[0103] The feed was a powder full-price feed, and no antibiotics were added in the feed. The composition and nutritional ingredients of the basic diet are shown in the following table.

[0104] Table 5 Feed composition and nutritional level, %

[0105]

[0106]

[0107] The chicken house is kept well ventilated, and the room temperature is maintained at 22-25℃. Before the breeding test, the equipment and the cage are cleaned and disinfected, the cage is thoroughly cleaned, and after drying, it is fumigated with potassium permanganate and formaldehyde. The test uses net flat breeding, uses bowl type waterer, free feeding and drinking, 24h light. Feed the test feed regularly, three times a day. Observe the animal group's mental state, feeding and drinking, and normal feces color every day, and record the animal group's daily mortality and morbidity.

[0108] 1.4 Sample collection and processing

[0109] 1.4.1 Growth performance

[0110] Record the daily feed consumption per unit, and weigh the empty stomach at 8:00 in the morning on the 43rd day before feeding, and weigh the body weight per unit.

[0111] Record the daily feed consumption and the remaining feed, and the mortality and elimination. Calculate the average initial weight, feed intake, average daily gain, and feed conversion ratio.

[0112] Daily feed intake / (g / d·bird) = Σ[(daily feed intake-daily remaining feed) / daily feeding amount] / feeding days;

[0113] Average daily gain / (kg / d·bird) = (average final weight-average initial weight) / feeding days;

[0114] Feed conversion ratio = total feed consumption during the test period / total weight gain during the test period.

[0115] Death rate = number of deaths / total number x 100%

[0116] 1.4.2 Detection of AKP, AST, ALT and LDH in serum

[0117] After weighing on the 43rd day, take 1 chicken per unit, take blood, stand for 2h, then centrifuge the serum at 3000r / min, and store it at -20℃. The AKP, AST, ALT and LDH contents are detected by spectrophotometry using a full-automatic biochemical analyzer.

[0118] 1.5 Data statistics and analysis

[0119] The test data is arranged and analyzed by Excel, and the one-way ANOVA program in SPSS 16.0 software is used for single factor variance analysis of statistical data, and Duncan's method is used for multiple comparison of data. The test results are expressed in the form of mean ± standard deviation, and P<0.05 is used as the standard for judging the significance of data difference.

[0120] 2 Results and analysis

[0121] Table 6 Effects of high concentration selenium exposure on growth performance of broilers at 22-42d

[0122]

[0123] Note 1: The results are expressed as mean ± standard deviation, and the same row data with different letters represent significant differences (P <0.05), the same letters or no letters represent no significant differences, and the same below.

[0124] Note 2: Control group 2 is the group of gavage with 3.15 mg / kg (Se) sodium selenite + 1% vitamin E; control group 3 is the group of gavage with 3.15 mg / kg (Se) sodium selenite + 1% taurine; control group 4 is the group of gavage with 3.15 mg / kg (Se) sodium selenite + 1% allicin, and the same below.

[0125] From the data in the table, compared with the control group, after gavage with 3.15 mg / kg (Se) sodium selenite, the average final weight of 42d broilers decreased significantly by 10.31% (P <0.05), the average daily feed intake of 22-42d decreased significantly by 9.02% (P <0.05), the average daily gain of 22-42d decreased significantly by 10.87% (P <0.05), and the feed conversion ratio increased by 5.20%. The mortality rate increased from 0% to 32.84%.

[0126] Compared with the sodium selenite model group, the average final weight of 42d in the sodium selenite + compound preparation group increased by 5.68%, the average daily feed intake of 22-42d increased by 4.27%, the average daily gain of 22-42d increased significantly by 7.21% (P <0.05), the feed conversion ratio of 22-42d decreased by 3.46%, and the mortality rate decreased significantly by 55.60% (P <0.05).

[0127] Compared with the sodium selenite model group, the average final weight of 42d in the sodium selenite + 1% vitamin E group (control group 2) increased by 0.30%, the average daily feed intake increased by 1.42%, the average daily gain decreased by 1.94%, and the feed conversion ratio decreased by 1.04%.

[0128] Compared with the sodium selenite model group, the average final weight of 42d in the sodium selenite + 1% taurine group (control group 3) increased by 2.06%, the average daily feed intake increased by 0.94%, the average daily gain increased by 0.43%, and the feed conversion ratio decreased by 2.06%.

[0129] Compared with the sodium selenite model group, the average final weight of 42d in the sodium selenite + 1% taurine group (control group 4) decreased by 0.53%, the average daily feed intake increased by 1.96%, the average daily gain decreased by 3.54%, and the feed conversion ratio increased by 1.03%.

[0130] Table 7 Effects of high concentration selenium exposure on serum ALT, AST, AKP and LDH of broilers at 42d

[0131]

[0132] From the data in the table, compared with the control group, the glutamic transaminase (AST), alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) of the sodium selenite group by gavage were significantly higher than those of the control group (P<0.05), showing that the effect of sodium selenite on liver damage of broilers was obvious. After adding the compound preparation, the glutamic transaminase (AST) was significantly reduced (P<0.05), and the alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) showed a downward trend, proving that the compound preparation provided by the application can reduce the damage of sodium selenite to the liver to a certain extent. The control groups 2, 3 and 4 had no obvious downward trend, proving that the single test substance cannot improve the liver damage caused by selenium poisoning.

[0133] The above examples are only illustrative of the present application and do not constitute a limitation on the protection scope of the present application. Any design identical or similar to the present application falls within the protection scope of the present application.

Claims

1. A complex formulation for alleviating selenium poisoning, characterized in that: 50-55% taurine, 2-5% vitamin E, 10-15% glutathione, 25-30% allicin and 5-15% carotene by mass percentage.

2. A feed for alleviating selenium poisoning, characterized in that: The basic daily ration and the compound preparation as claimed in claim 1.

3. The feed for alleviating selenium poisoning according to claim 2, wherein: The compound preparation is added in an amount of 0.5-2% by mass of the basic daily ration.

4. Use of the compound preparation for relieving selenium poisoning in claim 1 in the preparation of a feed additive for repairing the growth performance and liver damage of animals suffering from selenium poisoning.

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