Bacterial protein synthesis; Microbial Metabolite; Bacterial HSV-1; Endogenous Metabolite

土霉素是细菌芳香族聚酮家族的重要成员，是一类具有不同结构的天然化合物。土霉素由II型聚酮合酶合成，该酶通过丙二酰辅酶A延伸单元的连续脱羧缩合生成聚β-酮主链，然后经过环化酶、加氧酶、转移酶和其他剪裁酶修饰加工[2]。

在不同的动物中，土霉素治疗剂量（82.8mg/kg体重至1%体重/天）10天后有不同的效果。给予土霉素后，Morone Chrysops 的相对肝脏重量较高。牛奶和肌肉中土霉素的限量为100微克/千克，鸡蛋中为200微克，肝脏中为300微克，肾脏中为600微克。接受每公斤生物量含有 35–75 毫克土霉素 (OTC) 的治疗饲料的鱼在第 1 天给药，持续 7–14 天 [1]。

土霉素（OTC）是一种广谱抗生素，通过抑制细菌中的蛋白质合成起作用。它是细菌芳香族聚酮家族的重要成员，是一类结构多样的天然产物。OTC是由一种II型聚酮合酶合成的，该合酶通过丙二酰辅酶a延伸单元的连续脱羧缩合产生聚β酮骨架，随后被环化酶、氧化酶、转移酶和其他定制酶修饰。遗传和生化研究阐明了OTC生物合成中涉及的大部分步骤，本文将其作为II型聚酮生物合成的代表性案例研究进行详细介绍[2]。

Oxytetracycline (OTC) is employed in fish farms to contest or prevent bacterial infections. We simulated an OTC treatment at therapeutic level (75 mg kg(-1)) and at higher doses (150, 300 mg kg(-1)) for 10 days. A withdrawal period of 10 days was considered for treated carp, carrying out the same chemical and biochemical analyses (total glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and malondialdehyde). The aim was to obtain data related to the carryover in muscle and on variations in the antioxidant indicators in liver and kidney. The OTC residual levels in muscle showed a dose-response relationship. After 10 days of treatment at the recommended dose (75 mg kg(-1)), the mean value in muscle was 295 μg kg(-1). After 10 withdrawal days, residues in all treated groups were not entirely eliminated by fish. Residues of recommended 75 mg kg(-1) OTC dose were lower than the maximum permitted by EEC regulation: 100 μg kg(-1). Disturbance in the antioxidant systems in liver and kidney was recorded in (150, 300 mg kg(-1)) carp, as well as during the withdrawal period. A lowered superoxide dismutase activity and higher levels of catalase, glutathione peroxidase, glutathione reductase and glutathione were evaluated in liver, while in kidney only higher malondialdehyde and glutathione S-transferase concentrations were recorded for 300 mg kg(-1) dose. The therapeutic OTC dose exerted lower effects, and only in liver, enhancement of GPx and GR activities was recorded. After the withdrawal period, altered antioxidant responses in tissues were restored for all three OTC doses.[1]

Absorption, Distribution and Excretion
Readily absorbed following oral administration.
SERUM HALF-LIFE ... IN HORSES IS ... 15.7 HR & 10.5 HR AFTER IV & IM INJECTIONS, RESPECTIVELY. ... /A FACTOR/ MAY BE THE INFLUENCE OF DOSE-DEPENDENT KINETICS ... .
The percentage of an oral dose that is absorbed (when the stomach is empty) ... for oxytetracycline /is/ 60 to 80% ... After a single oral dose, the peak plasma concn /of oxytetracycline/ is attained in 2 to 4 hr. /It has a half-life/ in the range of 6 to 12 hr and ... frequently admin 2 to 4 times daily ... The admin of 250 mg every 6 hr produces peak plasma concn of 2 to 2.5 ug/mL ... Increasing the dosage above 1 g every 6 hr does not produce significantly higher plasma concn ... Approx 10 to 35% of a dose of oxytetracycline is excreted in active form in urine, in which it is detectable within 30 min and reaches a peak concn about 5 hr after it is admin.
/Oxytetracycline is/ bound to plasma proteins ... approx ... 20-25%.
/Absorption is/ much less complete from lower ... tract ... Biliary concn ... /is/ 5 to 10 times higher than ... plasma. /Tetracyclines/
For more Absorption, Distribution and Excretion (Complete) data for OXYTETRACYCLINE (20 total), please visit the HSDB record page.

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Biological Half-Life
BIOLOGIC HALF-LIFE ... MAY BE 3-4 DAYS IN ANURIA.
The serum half-life of oxytetracycline is 6 to 10 hours in adults with normal renal function and is reported to be 47 to 66 hours in patients with severe renal impairment. In patients with normal renal function, approximately 60 to 70 percent of a single oral dose of oxytetracycline is excreted in urine within 72 hours as active drug.
A two-way crossover study was conducted in crossbred male calves (6-8 months old) to determine the bioavailability, pharmacokinetics and dosage regimens for a long-acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline after intravenous and intramuscular administration were 7.8 hr and 24 hr, respectively. ....
The pharmacokinetic properties of oxytetracycline were studied following a single injection of a long-acting formulation (20 mg/kg body weight) into the semimembranosus muscle of healthy dogs and of dogs that had been experimentally infected with Ehrlichia canis. ... The mean apparent elimination half-life (t(1/2) beta) was significantly increased following infection. ... The absorption half-life (t(1/2) ab) was significantly decreased after infection.
SERUM HALF-LIFE ... IN HORSES IS ... 15.7 HR & 10.5 HR AFTER IV & IM INJECTIONS, RESPECTIVELY. ... /A FACTOR/ MAY BE THE INFLUENCE OF DOSE-DEPENDENT KINETICS ... .

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
A number of reviews have stated that tetracyclines are contraindicated during breastfeeding because of possible staining of infants' dental enamel or bone deposition of tetracyclines. However, a close examination of available literature indicates that there is not likely to be harm in short-term use of oxytetracycline during lactation because milk levels are low and absorption by the infant is inhibited by the calcium in breastmilk. Short-term use of oxytetracycline is acceptable in nursing mothers. As a theoretical precaution, avoid prolonged or repeat courses during nursing. Monitor the infant for rash and for possible effects on the gastrointestinal flora, such as diarrhea or candidiasis (thrush, diaper rash).
◉ Effects in Breastfed Infants
No adverse effects were noted in an unspecified number of breastfed infants whose mothers were taking oral oxytetracycline 1.5 or 2 grams daily for 3 days. Ages of the infants and extent of breastfeeding were not stated.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
SIMULTANEOUS ADMIN IRON AS FERROUS SULFATE REDUCED ABSORPTION & CAUSED SIGNIFICANT DECR IN SERUM CONCN OF ... OXYTETRACYCLINE ... IN MAN. ... MILK GIVEN SIMULTANEOUSLY REDUCED ABSORPTION OF ... OXYTETRACYCLINE BY ABOUT 50% ... .
INCR CONCN OF OXYTETRACYCLINE IN NASAL MUCUS DUE TO BROMHEXINE TREATMENT ... ATTRIBUTED TO EVAPORATION OF THE LESS VISCOUS MUCUS, ARISING FROM BROMHEXINE TREATMENT, RATHER THAN INCR MEMBRANE PERMEABILITY.
... OXYTETRACYCLINE MAY CAUSE UNPREDICTABLE FLUCTUATIONS IN BLOOD GLUCOSE LEVELS ... BY INCR HALF-LIFE OF INSULIN. ... ALSO ... WHEN OXYTETRACYCLINE & TOLBUTAMIDE ... USED CONCURRENTLY.
Striking antagonism between penicillin and tetracyclines has been observed clinically in pneumococcal meningitis ... /Tetracyclines/
For more Interactions (Complete) data for OXYTETRACYCLINE (10 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Swiss mice oral 7200 mg/kg /hydroxytetracycline monohydrochloride/

[1]. Transferability of oxytetracycline (OTC) from feed to carp muscle and evaluation of the antibiotic effects on antioxidant systems in liver and kidney. Fish Physiol Biochem, 2014.

[2]. Oxytetracycline biosynthesis. J Biol Chem. 2010 Sep 3;285(36):27509-15.

[3]. A New Treatment Method for Herpes Simplex Virus Type 1-related Skin Lesions. Scientific & Academic. 2019; 8(1): 6-8.

Oxytetracycline (internal use) can cause developmental toxicity according to state or federal government labeling requirements.
Oxytetracycline is a tetracycline used for treatment of infections caused by a variety of Gram positive and Gram negative microorganisms including Mycoplasma pneumoniae, Pasteurella pestis, Escherichia coli, Haemophilus influenzae (respiratory infections), and Diplococcus pneumoniae. It has a role as an antibacterial drug, a protein synthesis inhibitor, an antimicrobial agent, an anti-inflammatory drug and a bacterial metabolite. It is a tautomer of an oxytetracycline zwitterion.
A tetracycline analog isolated from the actinomycete streptomyces rimosus and used in a wide variety of clinical conditions.
Oxytetracycline anhydrous is a Tetracycline-class Antimicrobial.
Terramycin has been reported in Streptomyces anthocyanicus, Streptomyces varsoviensis, and other organisms with data available.
A TETRACYCLINE analog isolated from the actinomycete STREPTOMYCES rimosus and used in a wide variety of clinical conditions.

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Drug Indication
Oxytetracycline is indicated for treatment of infections caused by a variety of Gram positive and Gram negative microorganisms including Mycoplasma pneumoniae, Pasteurella pestis, Escherichia coli, Haemophilus influenzae (respiratory infections), and Diplococcus pneumoniae.

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Mechanism of Action
Oxytetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Oxytetracycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane.
Tetracyclines inhibit bacterial protein synthesis by binding to the 30 S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex. They enter gram-negative bacteria by passive diffusion through the hydrophilic channels formed by the porin proteins of the outer cell membrane, and active transport by an energy-dependent system that pumps all tetracyclines across cytoplasmic membrane. Although permeation of these drugs into gram-positive bacteria is less well understood, it also is energy requiring. At high concn, these cmpd impair protein synthesis in mammalian cells. However, because mammalian cells lack the active transport system found in bacteria, and the ribosomal target is less sensitive, tetracyclines are selectively active against bacteria. /Tetracyclines/
The tetracycline antibiotics ... can produce neuromuscular blockade, possibly by chelation of Ca+2. /Tetracyclines/

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Therapeutic Uses
Mesh Heading: anti-bacterial agents
Antibiotics, Tetracycline
... Possess wide range of antimicrobial activity against gram-positive and gram-negative bacteria ... some microorganisms innately insensitive to many chemotherapeutic agents, such as rickettsiae, mycoplasma, chlamydia agents of lymphogranuloma venerum, psittacosis, inclusion conjunctivitis, and trachoma and amebae. /Tetracyclines/
The tetracyclines are active against a wide range of aerobic and anaerobic gram-positive and gram-negative bacteria. They also are effective against some microorganisms that are resistant to cell-wall-active antimicrobial agents, such as Rickettsiae, Coxiella burnetii, Mycoplasma pneumoniae, Chlamydia spp, Legionella spp, Ureaplasma, some atypical mycobacteria, and Plasmodium spp. They are not active against fungi. /Tetracyclines/
For more Therapeutic Uses (Complete) data for OXYTETRACYCLINE (28 total), please visit the HSDB record page.

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Drug Warnings
GENERIC INEQUIVALENCE HAS BEEN DEMONSTRATED FOR SOME OXYTETRACYCLINE FORMULATIONS, ALTHOUGH INDIVIDUAL VARIATION PREVENTED SIGNIFICANT DIFFERENCES BEING SHOWN IN ALL BUT MOST EXTREME CASES.
FOOD, MILK, NONSYSTEMIC ANTACIDS & IRON PREPN INTERFERE WITH ORAL ABSORPTION.
... Not active against any true viruses, yeasts, or fungi. /Tetracyclines/
Topical admin is best avoided because of high risk of sensitization, except for use in eye ... Should never be injected intrathecally. /Tetracyclines/
For more Drug Warnings (Complete) data for OXYTETRACYCLINE (38 total), please visit the HSDB record page.

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Pharmacodynamics
Oxytetracycline is known as a broad-spectrum antibiotic due to its activity against such a wide range of infections. It was the second of the tetracyclines to be discovered. Oxytetracycline, like other tetracyclines, is used to treat many infections common and rare. Its better absorption profile makes it preferable to tetracycline for moderately severe acne, but alternatives sould be sought if no improvement occurs by 3 months.

460.148

C, 57.39; H, 5.25; N, 6.08; O, 31.27

79-57-2

Oxytetracycline hydrochloride;2058-46-0;Oxytetracycline dihydrate;6153-64-6;Oxytetracycline calcium;7179-50-2

54675779

Light yellow to yellow solid powder

1.7±0.1 g/cm3

727.8±60.0 °C at 760 mmHg

183 °C

394.0±32.9 °C

0.0±2.5 mmHg at 25°C

1.762

0.56

201.85

7

10

2

33

1000

6

O[C@@]12C(=O)C(C(=O)N)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]([C@@H]1[C@@](O)(C)C3C=CC=C(C=3C(=O)C1=C2O)O)O

OWFJMIVZYSDULZ-PXOLEDIWSA-N

InChI=1S/C22H24N2O9/c1-21(32)7-5-4-6-8(25)9(7)15(26)10-12(21)17(28)13-14(24(2)3)16(27)11(20(23)31)19(30)22(13,33)18(10)29/h4-6,12-14,17,25-26,28,30,32-33H,1-3H3,(H2,23,31)/t12-,13-,14+,17+,21-,22+/m1/s1

(4S,4aR,5S,5aR,6S,12aR)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide

oxytetracycline; 79-57-2; Terramycin; Oxyterracine; Oxytetracyclin; Oxymycin; Terrafungine; Oxyterracin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~108.59 mM)
H2O : ~0.67 mg/mL (~1.46 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.43 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.43 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (5.43 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。