Toxicity of tetracycline and its transformation products to a phosphorus removing Shewanella strain.

Tetracycline (TC) as an emerging contaminant has raised serious concerns about its toxicity and removal in wastewater treatment processes. The more toxic transformation products of TC, 4-epitetracycline (ETC), anhydrotetracycline (ATC) and 4-epianhydrotetracycline (EATC) are also widely detected. This study investigated the antibacterial and bactericidal activity of TC, ETC, ATC, EATC against Shewanella sp, using Escherichia coli and Pseudomonas aeruginosa strains as quality controls. Further, batch assays were conducted to investigate the inhibition of these antibiotics on the phosphorus removal of the Shewanella strain, and removal mechanisms of TC and its transformation products (TCs). The inhibition on phosphorus removal by the Shewanella strain at 20 mg L-1 was in the order of ATC > EATC > TC > ETC. COD removal, poly-P accumulation and glycogen synthesis by the Shewanella strain were also inhibited. Biodegradation was the main removal mechanism of TC and ETC, while adsorption was the main one of ATC and EATC. This study helps to further understand the structure-activity relationship of TC.

Chronic exposure of river sediments to environmentally relevant levels of tetracycline affects bacterial communities but not denitrification rates.

The effects of tetracycline (TC) at chronic sub-inhibitory exposure concentrations on benthic denitrification rates and bacterial communities were explored. River sediments were continuously exposed to different TC concentrations (0.5, 20 and 10,000 µg L(-1)) for 2 weeks in flow-through reactors allowing denitrification and bacterial growth conditions. Bacterial communities were fingerprinted by Denaturing Gradient Gel Electrophoresis of 16S rRNA gene amplification products. Cultivable denitrifiers enriched from the sediment were tested for TC resistance (2-128 mg L(-1)). Denitrification rates were unaffected by exposure to TC, regardless of concentration. In contrast, the bacterial community composition changed significantly from sub-inhibitory (ng-µg L(-1)) to therapeutic (mg L(-1)) exposure concentrations. Furthermore the cultivable denitrifiers showed a high TC sensitivity (<4 mg L(-1)). Maintenance of efficient benthic denitrification rates, even at the highest level of TC exposure most likely originated from an adaptation of the autochthonous bacterial community where dominant species become those that acquire, or already have resistance to antibiotics.

Effects of residual antibiotics in groundwater on Salmonella typhimurium: changes in antibiotic resistance, in vivo and in vitro pathogenicity.

An outbreak-causing strain of Salmonella enterica serovar Typhimurium was exposed to groundwater with residual antibiotics for up to four weeks. Representative concentrations (0.05, 1, and 100 µg L(-1)) of amoxicillin, tetracycline, and a mixture of several other antibiotics (1 µg L(-1) each) were spiked into artificially prepared groundwater (AGW). Antibiotic susceptibility analysis and the virulence response of stressed Salmonella were determined on a weekly basis by using human epithelial cells (HEp2) and soil nematodes (C. elegans). Results have shown that Salmonella typhimurium remains viable for long periods of exposure to antibiotic-supplemented groundwater; however, they failed to cultivate as an indication of a viable but nonculturable state. Prolonged antibiotics exposure did not induce any changes in the antibiotic susceptibility profile of the S. typhimurium strain used in this study. S. typhimurium exposed to 0.05 and 1 µg L(-1) amoxicillin, and 1 µg L(-1) tetracycline showed hyper-virulent profiles in both in vitro and in vivo virulence assays with the HEp2 cells and C. elegans respectively, most evident following 2nd and 3rd weeks of exposure.

The effects of residual tetracycline on soil enzymatic activities and plant growth.

A pot trial was carried out to investigate the adverse effects of tetracycline (TC) on soil microbial communities, microbial activities, and the growth of ryegrass (Lolium perenne L). The results showed that the presence of TC significantly disturbed the structure of microbial communities and inhibited soil microbial activities in terms of urease, acid phosphatase and dehydrogenase (p < 0.05). Plant biomass was adversely influenced by TC, especially the roots with a reduction of 40% when compared with the control. Furthermore, TC decreased the assimilation of phosphorus by the plant although the concentration of phosphorus was increased by 20% due to decreased plant biomass. TC seemed to increase the concentration of dissolved organic carbon (by 20%) in soil. The findings implied that the agricultural use of animal manure or fishpond sediment containing considerable amounts of antibiotics may give rise to ecological risks.

[Effect of hepatophyt on the choleretic function of the liver damaged by tetracycline]. / Vliianie gepatofita na zhelchevydelitel'nuiu funktsiiu pecheni pri povrezhdenii ee tetratsiklinom.

In experimental injury of the liver in Wistar-line white rats induced by tetracycline the course therapeutic and prophylatic administration of the dry extract "Hepatophyt" in a dose of 0.1 g/kg inhibits the negative effect of tetracycline and promotes stimulation of choleretic and antitoxic functions of the liver. The dry extract was derived from the herbal mix of the same name, used in the practice of Tibetan medicine against liver diseases.

Comparison of silver nitrate and tetracycline as pleural sclerosing agents in rabbits.

The ideal agent to produce pleurodesis has not been identified. Tetracycline, the drug used most commonly in the 1980s, is no longer available. Talc either aerosolized or in a slurry is the agent used just most commonly at the present time, but there are concerns about its safety. Another possibility is silver nitrate, which was widely used in the past, but was abandoned on account of side effects. We hypothesized that lower concentrations of silver nitrate than had been used in the past would be effective in creating a pleurodesis in rabbits. The following medications in a total volume of 2 mL were instilled intrapleurally in three groups of ten anesthetized rabbits: 0.25% or 0.50% silver nitrate and 35 mg/kg tetracycline. Twenty-eight days after the injection, the animals were sacrificed and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.50% silver nitrate produced an effective pleurodesis. The mean degree of gross pleurodesis in the rabbits that received 0.50% silver nitrate (3.4 +/- 1.2) did not differ significantly from that of the rabbits that received tetracycline (3.5 +/- 0.7) (scale 0 to 4). The mean degree of microscopic pleural fibrosis in the rabbits that received 0.50% silver nitrate (3.4 +/- 0.7) did not differ significantly from that of the rabbits that received tetracycline (3.9 +/- 0.3). However, 0.25% silver nitrate was ineffective in creating pleural fibrosis, either grossly or microscopically. No rabbits died after the intrapleural injection of the drugs. There were no observed side effects after the injection of silver nitrate. The present study demonstrates that 0.50% silver nitrate instilled into the pleural space is an effective agent for producing pleurodesis in the rabbit; its effect is comparable to tetracycline 35 mg/kg. This agent should be compared with tetracycline derivatives and talc in studies in humans.

[Antimicrobial sensitivity and treatment of Helicobacter pylori infections].

Helicobacter pylori (HP) is considered the etiological agent of chronic active gastritis and suspicion is strong that it plays an important role in duodenal ulcer. Recently, several clinical studies reported that eradication of HP markedly reduces the frequency of ulcer relapse. Triple-drug treatment, including a bismuth salt and 2 antibiotics (usually metronidazole with either amoxycillin or tetracycline) is considered the treatment of choice. It has been shown that the most important factor for predicting success of treatment is the sensitivity of HP to metronidazole, which varies considerably. In the present study we evaluated antimicrobial susceptibility of 18 HP clinical isolates, as well as effectiveness of triple therapy for eradicating HP infections in 65 patients. In vitro, HP was highly sensitive to amoxycillin, erythromycin and tetracycline (100%), and also to metronidazole and tinidazole (94%). Sensitivity to chloramphenicol was low (50%). In our clinical study, the overall eradication rate was 66%; it was higher among women (80%) than men (54%), probably due to better compliance. It is concluded that HP strains in Israel are highly sensitive to metronidazole and that triple therapy is effective, providing compliance is good.

Comparative toxicity and carcinogenicity studies of tetracycline and oxytetracycline in rats and mice.

Two-year toxicity and carcinogenicity studies of oxytetracycline hydrochloride and tetracycline hydrochloride, two structurally similar and widely used antibiotics, were performed in F344/N rats and B6C3F1 mice. Rats and mice were continuously exposed via their diet to the following levels of antibiotic: oxytetracycline HCl--rats 0, 25,000, or 50,000 ppm; mice 0,6,300, or 12,500 ppm; tetracycline HCl--rats and mice 0, 12,500, or 25,000 ppm. On a milligram per kilogram of body weight basis these exposures represent doses that are 20 to 140 times daily human therapeutic doses. Dose-related increased survival was noted among oxytetracycline-treated male rats and tetracycline-treated female rats and male mice, while treatment-related reduced body weight gain occurred in oxytetracycline- and tetracycline-treated mice. Microscopic changes included fatty metamorphosis and focal cellular change in livers of oxytetracycline-treated male rats and basophilic cytoplasmic and clear cell change in livers of tetracycline-treated male rats. The only neoplastic changes were a marginally increased trend in pheochromocytoma of the adrenal medulla (equivocal evidence only) among oxytetracycline-exposed male rats (12/50 controls, 19/50 low dose, 24/50 high dose) and an increased incidence of pituitary adenoma or adenocarcinoma among high-dose oxytetracycline-treated female rats (20/50 controls, 32/50 high dose). Although oxytetracycline and tetracycline appeared to increase the incidence of pituitary hyperplasia in high-dose male and female rats, respectively, the total incidence of proliferative changes (hyperplasia, adenoma, and adenocarcinoma) was not affected by antibiotic exposure. The results from these studies therefore support the notion that neither antibiotic is carcinogenic in rodents. There were several negative trends suggesting possible protective effects by both these tetracycline analogs against certain spontaneous neoplastic and non-neoplastic changes.

[Action of hepatoprotective agents in a tetracycline lesion of the liver]. / Deistvie gepatozashchitnykh sredstv pri tetratsiklinovom porazhenii pecheni.

Comparative efficacy of hepatoprotective agents in tetracycline affection of the liver is discussed. The affection was induced by daily intragastric administration of the antibiotic in a dose of 0.5 g/kg body weight to Wistar albino rats. The level of the hepatocyte affection and the efficacy of the hepatoprotective agents were judged by changes in the biligenic, glycogen producing, antitoxic and absorbing-excretory functions of the liver and the activity of lipid peroxidation (LPO) and serum enzymes. In acute tetracycline intoxication there was observed suppression of cholopoiesis, induction of LPO, increased permeability of hepatocyte membranes, lowered stabilizing activity of bile and decreased detoxicating and absorbing-excretory capacity of the liver. The highest correcting effect of the hepatoprotective agents was shown with respect to cholopoiesis, carbohydrate metabolism and lipoperoxidation of hepatocyte membranes. The efficacy of silibor in tetracycline affection of the liver was close to that of Essentiale and legalon and superior to that of LIV-52.

[Effectiveness of legalon and essentiale in a tetracycline-induced liver lesion]. / Effektivnost' legalona i éssentsiale pri porazhenii pecheni tetratsiklinom.

It was shown in the experiments with albino rats that legalon and essentiale had a pronounced hepatoprotective effect in tetracycline affections of the liver. They retarded the increase in the activity of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in blood serum, prevented suppression of cholopoiesis by tetracycline and inhibited lipid peroxidation. The drugs may be used for prevention and treatment of tetracycline affections of the liver.

[Seasonal effectiveness of antioxidants in tetracycline lesions of the liver]. / Sezonnaia éffektivnost' antioksidantov pri tetratsiklinovykh porazheniiakh pecheni.

The seasonal characteristic features of the efficacy of antioxidants in tetracycline affections of the liver were revealed in the experiments with 182 noninbred albino male rats. It was shown that sodium selenite had the most pronounced hepatoprotective effect in autumn and winter, while vitamin E was most effective in spring and summer. The combination of sodium selenite with vitamin E recovered impaired bile excretion in autumn, spring and summer. In winter, the recovery was less effective. It is concluded that the time factor plays a significant role in tetracycline hepatotoxicity and efficacy of antioxidants in tetracycline affections of the liver.

[Liver-protective effect of tocopherol acetate and selenium-containing preparations in tetracycline antibiotic lesions of the liver]. / Gepatozashchitnyi éffekt tokoferola atsetata i selensoderzhashchikh preparatov pri porazhenii pecheni tetratsiklinovymi antibiotikami.

It was shown on 99 male albino rats that vitamin E, sodium selenite and Astragalus. L. infusion used separately lowered the toxic effect of tetracycline on the liver, while the use of vitamin E in combination with sodium selenite or Astragalus L. infusion prevented such an effect of the antibiotic. This was evident from the decreased levels of lipid peroxidation products, i.e. diene conjugates and malonic dialdehyde in the blood and liver, and a simultaneous increase in the ratio of sulfhydryl and disulfide groups in these biosubstrates. Parallelism of the changes in these indices of the blood and liver was observed. It is suggested that lipid peroxidation plays an important part in the pathogenesis of liver affection with tetracyclines. The combined use of vitamin E and selenium-containing drugs is considered advisable for the prophylaxis and treatment of such affections.