Arzneimittelforschung. 1982;32(3):237-41.
Comparative evaluation of the effects of tetracycline, rolitetracycline and doxycycline on some blood parameters related to liver function.

Bocker R, Estler CJ, Muller S, Pfandzelter C, Spachmuller B.

A comparative study was made on the effects of tetracycline (TC), rolitetracycline (RTC), and doxycycline (DC) at doses of 10-100 micrograms/g i.v. on serum GOT, GPT, bilirubin and urea levels of male and female mice. All tetracyclines at doses of 50-100 micrograms/g caused an increase of serum GOT and GPT activities in females after 2-8 h. This effect was less pronounced in males. The serum urea levels were markedly raised by TC and DC (50-100 micrograms/g) and RTC (10-100 micrograms/g). This effect was produced only in females. It was long-lasting (up to 8 h) after TC and RTC and more transient after DC. Likewise the tetracyclines affected the serum bilirubin only in females but not in males. All tetracyclines (25-100 micrograms/g) increased the amount of unconjugated and total bilirubin. This effect was most pronounced after TC, which also reduced the level of conjugated bilirubin.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7200783&dopt=Abstract antibiotics, tetracycline




J Infect Dis. 1976 Feb;133(2):185-93.
Binding of antibiotics to the human intracellular erythrocyte proteins hemoglobin and carbonic anhydase.

Kornguth ML, Kunin CM.

The interaction between human erythrocyte lysates and antibiotics was studied, and the effect of intracellular components on the activity and binding of the drugs was determined. Lysates inhibited antibacterial activity of penicillin G, dicloxacillin, tetracycline, and minocycline to about the same extent as did human plasma. Dicloxacillin activity was the most inhibited, followed by the activities of penicillin G, minocycline and tetracycline. All four antibiotics bound to human hemoglobin, as determined by gel filtration methods. Heme-free globin was also effective in binding the antibiotics. In addition, minocycline and tetracycline were bound to another erythrocytic protein, which, on the basis of electrophoretic mobility, molecular size, and localization, has been identified as carbonic anhydrase. Experiments with pure preparations of carbonic anhydrase revealed that the C isozyme is the major binder of the tetracyclines and that zinc is required for binding. Tetracyclines did not inhibit enzymatic activity of carbonic anhydrase.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=812928&dopt=Abstract antibiotics, tetracycline




Z Ernahrungswiss. 1980 Sep;19(3):173-8.
The effect of vitamin B12 on tetracycline-induced fatty liver.

Mikhail TH, Ibrahim KM, Awadallah R, Mona E.

The effect of vitamin B12 on the metabolic alterations due to tetracycline toxicity was studied experimentally on laboratory animals. Treatment of Sprague-Dawley rats with 120 or 250 mg tetracycline (i.p.) per kg per day for two or three days caused an accumulation of lipids, mainly triglycerides in the liver of 75% of animals studied, while phospholipid level tend to decrease. These doses are approximately twice and four times the recommended maximum dose for man. In the present work no direct relationship was observed between dose of tetracycline and hepatic accumulation of triglyceride, although livers of rats treated with 250 mg tetracycline/kg appeared uniformly pale yellow. Elevated serum triglyceride was found predominantly in rats treated with 120 mg/kg, while there was no obvious difference between serum triglyceride of rats treated with 250 mg tetracycline and control rats, indicating a block in the release of hepatic triglycerides. Where protection by vitamin B12 was studied, the vitamin was given i.m. (50 microgram/animal) 3 hours before the injection of 120 mg tetracycline per kg. There was a good evidence that lipid abnormalities caused by tetracycline improved by vitamin B12. Thus both hepatic and serum total lipid and triglycerides were significantly lower than those of rats treated with tetracycline, although hepatic total cholesterol was significantly increased as in case of tetracycline only.

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Biochemistry. 1996 Jul 23;35(29):9385-91.
Mercaptide formed between the residue Cys70 and Hg2+ or Co2+ behaves as a functional positively charged side chain operative in the Arg70-->Cys mutant of the metal-tetracycline/H+ antiporter of Escherichia coli.

Someya Y, Yamaguchi A.

Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Japan.

The bacterial tetracycline/H+ antiporter (TetA) mediates active efflux of a chelation complex of tetracycline with a divalent cation such as Mg2+, Co2+, or Mn2+ [Yamaguchi, A., Udagawa, T., & Sawai, T. (1990a) J. Biol. Chem. 265, 4809-4813]. The positive charge of Arg70 in the antiporter is important for the transport function [Yamaguchi, A., Someya, Y., & Sawai, T. (1992c) J. Biol. Chem. 267, 19155-19162]. Out of six site-directed mutants of Arg70, only the Lys70 mutant retained moderate transport activity, whereas the Ser70, Ala70, Trp70, Leu70, and Asp70 mutants had no or extremely low transport activity. In this study, we constructed the Cys70 mutant and found that the Cys70 mutant showed, unexpectedly, a significant activity comparable to that of the Lys70 mutant in the presence of Co2+ ions, whereas it showed very low activity as well as the Ala70 mutant in the presence of Mg2+ or Mn2+ ions. Hg2+, which is known to be a cysteine specific modifier but has no ability to form a complex with tetracycline, caused a dramatic increase in the Vmax value of Co(2+)-dependent tetracycline transport mediated by the Cys70 mutant without affecting the k(m) value, whereas activities of the wild-type and the Lys70 and Ala70 mutants were not affected by Hg2+, Hg2+ alone without Co2+ could not support the transport activity at all, because Hg2+ does not form a chelation complex with tetracycline. These observations suggest that a mercaptide formed between the SH group of Cys70 and Hg2+ or Co2+ works as a positively charged side chain like that of Arg or Lys. When the SH group of the Cys70 mutant was masked with modification by sulfhydryl reagents, the residual activity was no longer affected by Hg2+. Inversely, when the Cys70 mutant was preincubated with Hg2+, it was protected from the inactivation by sulfhydryl reagents. These observations also confirm the mercaptide formation between the Cys70 and a divalent cation as a functional side chain.

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Arthritis Rheum. 1987 Apr;30(4):448-50.
Failure of tetracycline therapy in early Lyme disease.

Dattwyler RJ, Halperin JJ.

We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migrans with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3580012&dopt=Abstract antibiotics, tetracycline




J Assoc Physicians India. 2000 Sep;48(9):891-4.
Intracystic tetracycline therapy for hypofunctioning cystic thyroid nodules.

Garg MK, Satija L, Khanna SK, Saini JS.

Department of Radiology, Command Hospital (SC), Pune, India.

OBJECTIVES: Hypofunctioning benign cystic thyroid nodules are a common occurrence in iodine deficient region. There are reports of resolution of recurrent thyroid cysts with tetracycline instillation. Hence we conducted a study in 20 patients with hypofunctioning benign cystic thyroid nodules to document response to intracystic instillation of tetracycline as a primary modality of treatment. METHODS: Twenty patients were thoroughly investigated for the presence of malignancy clinically, radiologically and cytologically. One milliliter of tetracycline was instilled under ultrasonographic guidance. Response to therapy was assessed clinically and ultrasonographically at one, three, six and 12 months. RESULTS: Study group comprised of five male and 15 female patients with mean age 30 +/- 8 years. Initial mean volume of nodules was 15 +/- 7 ml (6 to 27 ml), which was decreased to 3 +/- 3 ml at one month, 2 +/- 3 ml at three months, and 1 +/- 2 ml at six months. Maximum number of patients (75%) responded within three months, however two patients required reaspiration and reinstallation of tetracycline. Ultrasonography revealed fibrotic scar as thick wall with internal echodensities in six patients (30%) six month after sclerotherapy. There was high rate of patient satisfaction, as cosmetically tetracycline did not leave any scar, which was unavoidable with surgery. Six patients (30%) reported mild pain after injection, and one patient developed redness at the site of injection. CONCLUSIONS: Intracystic tetracycline sclerotherapy is highly effective as primary mode of treatment in hypofunctioning benign cystic thyroid nodule in selected group of patients not at high risk of malignancy.

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JAMA. 1978 Feb 27;239(9):853-4.
Single-dose tetracycline therapy for shigellosis in adults.

Pickering LK, DuPont HL, Olarte J.

Forty-two adults who had Shigella isolated from stool (26 symptomatic, 16 asymptomatic) received a single oral dose of tetracycline hydrochloride (2.5 g). Minimal inhibitory concentrations of the 42 isolates demonstrated that 41% were sensitive to tetracycline. Sixteen of 18 patients with diarrhea who had tetracycline-resistant Shigella and all eight patients with diarrhea who had tetracycline-sensitive Shigella were clinical well and had Shigella-negative stools 48 hours after therapy. Fifteen of 16 asymptomatic patients demonstrated clearing of Shigella from stool within 48 hours of therapy. Single-dose tetracycline therapy is effective in the treatment of Shigella regardless of clinical expression of illness or in vitro sensitive of the organism.

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Arch Dermatol Res. 1978 Nov 10;263(2):135-8.
Effects of tetracycline on the absorption of 65zinc in rats.

Weismann K, Knudsen L, Hoyer H.

The effects of tetracycline on the absorption of orally ingested 65Zn was studied on rats by whole body counting assay. 65Zn was given as a single dose to groups of rats, five in each, which were started on tetracycline. Tetracycline was given in daily doses of 25 mg, 50 mg, 100 mg, and 200 mg for 10 days. From the 6th day of the study, 65Zn retention when plotted against time in a semilog plot, approximated linearity. The net absorption of 65Zn in the various groups was determined by extrapolating to zero time the linear curve segment of individual retention curves. Except for the lowest tetracycline dosage, tetracycline significantly impaired 65Zn absorption. The elimination rate of retained 65Zn from the 6th day was significantly higher in the group receiving 200 mg tetracycline as compared with the control group.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=104665&dopt=Abstract antibiotics, tetracycline