Author: Alberto Portigliatti Pomeri
Date: 25/04/2011


Lavoro svolto da Alberto Portigliatti Pomeri


The fluorinated 4-quinolones, such as ciprofloxacin (CIPRO™), moxifloxacin (AVELOX™), and gatifloxacin (TEQUIN™), are orally effective for the treatment of a wide variety of infectious diseases and have relatively few side effects.


Compounds available in the U.S. contain a carboxylic acid moiety at position 3 of the primary ring structure. Many newer fluoroquinolones also contain a fluorine substituent at position 6 and a piperazine moiety at position 7.

Mechanism of Action

The quinolone antibiotics target bacterial DNA gyrase and topoisomerase IV. For many gram positive bacteria, topoisomerase IV is the primary target. For many gram-negative bacteria, DNA gyrase is the primary quinolone target. The quinolones inhibit gyrase-mediated DNA supercoiling at concentrations that correlate well with their effective antibacterial actions. Mutations of gyrA can confer resistance to these drugs. Topoisomerase IV separates catenated DNA molecules that result from DNA replication, and also is a target for quinolones.

Antibacterial Spectrum

Quinolones Versus Gram +

S. aureusS. pyogenesS. pneumoniaeE. faecalisE. faecium
Moxifloxacina (*)++++++++±

( * ) active also against chlamydia, legionella, mycoplasma, brucella, mycobacterium (including mycobacterium tuberculosis).

Quinolones Versus Gram -

E. ColiK. pneumoniaeEnterebacter spCitrobacter sp.Serratia marcescensShigella sp
Nalidixic acid++±---
Salmonella spProteus sp P. aeruginosaHaemophilus spNeisseriaM catarrhalis
Nalidixic acid-+-++++-

The fluoroquinolones are potent bactericidal agents against a broad variety of microorganisms, as outlined under Therapeutic Uses. Fluoroquinolones have good activity against staphylococci but not against methicillin-resistant strains. Activity against streptococci is limited to a subset of the quinolones, including levofloxacin (LEVAQUIN™), gatifloxacin (TEQUIN™), and moxifloxacin (AVELOX™).
Several intracellular bacteria are inhibited by fluoroquinolones; these include species of Chlamydia, Mycoplasma, Legionella, Brucella, and Mycobacterium (including Mycobacterium tuberculosis). Ciprofloxacin, ofloxacin (FLOXIN™), and pefloxacin inhibit M. fortuitum, M. Kansasii, and M. tuberculosis.

Moxifloxacin and pyrazinamide susceptibility testing in a complex case of multidrug-resistant tuberculosis. 2011


Resistance to quinolones may develop via mutations in the bacterial chromosomal genes
encoding DNA gyrase or topoisomerase IV or by active transport of the drug out of the bacteria.
No quinolone-inactivating mechanisms have been identified. Resistance has increased, especially in Pseudomonas and staphylococci. Fluoroquinolone resistance also is increasing in C. jejuni, Salmonella, Neisseria gonorrhoeae, and S. pneumoniae.

Characterization of nalidixic Acid-resistant and fluoroquinolone-reduced susceptible salmonella typhimurium in Swine. 2011

Absorption, Fate, And Excretion

The quinolones are well absorbed after oral administration and are widely distributed. Peak serum levels of the fluoroquinolones occur within 1–3 hours of an oral dose of 400 mg. Relatively low serum levels are reached with norfloxacin and limit its usefulness to the treatment of urinary tract infections. Food does not impair oral absorption but may delay the time to peak serum concentrations.
The volume of distribution of quinolones is high, with concentrations in urine, kidney, lung and prostate tissue, stool, bile, and macrophages and neutrophils higher than serum levels. Quinolone concentrations in CSF, bone, and prostatic fluid are lower than in serum.
Pefloxacin and ofloxacin levels in ascites fluid approach serum levels, and ciprofloxacin, ofloxacin, and pefloxacin have been detected in human breast milk.
Most quinolones are cleared predominantly by the kidney, and dose must be adjusted for renal failure. Pefloxacin and moxifloxacin are metabolized predominantly by the liver and should not be used in patients with hepatic failure.


Urinary Tract Infections
Norfloxacin is approved for use in the U.S. only for urinary tract infections. The fluoroquinolones are more efficacious than trimethoprim–sulfamethoxazole for the treatment of urinary tract infections.

Norfloxacin, ciprofloxacin, and ofloxacin are effective for the treatment of prostatitis caused by sensitive bacteria.

Sexually Transmitted Diseases
The quinolones are contraindicated in pregnancy. Fluoroquinolones lack activity for Treponema pallidum but have activity in vitro against N. gonorrhoeae, Chlamydia Trachomatis, and Haemophilus ducreyi.

Gastrointestinal and Abdominal Infections
For traveler’s diarrhea (frequently caused by enterotoxigenic E. coli), the quinolones are equal to trimethoprim–sulfamethoxazole in effectiveness. Norfloxacin, ciprofloxacin, and ofloxacin given for 5 days all are effective in the treatment of patients with shigellosis, with even shorter courses effective in many cases. Ciprofloxacin and ofloxacin cure most patients with enteric fever caused by S. typhi, as well as bacteremic nontyphoidal infections in AIDS patients. Shigellosis is treated effectively with either ciprofloxacin or azithromycin. The in vitro ability of the quinolones to induce the Shiga toxin (the cause of the hemolytic-uremic syndrome) in E. coli suggests that the quinolones should not be used for Shiga toxin–producing E. coli.

Shiga toxin-producing Escherichia coli urinary tract infection associated with hemolytic-uremic syndrome in an adult and possible adverse effect of ofloxacin therapy.2000

Respiratory Tract Infections
The major limitation to the use of quinolones for the treatment of community-acquired pneumonia and bronchitis was the poor activity against S. pneumoniae and anaerobic bacteria. Many of the newer fluoroquinolones, including gatifloxacin and moxifloxacin, have excellent activity against S. pneumoniae and have shown efficacy comparable to b-lactam antibiotics. The fluoroquinolones have activity against the rest of the common respiratory pathogens, including H. influenzae, Moraxella catarrhalis, S. aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. Either a fluoroquinolone (ciprofloxacin or levofloxacin) or azithromycin is the antibiotic of choice for L. pneumophila.

Bone, Joint, and Soft Tissue Infections
The treatment of chronic osteomyelitis requires prolonged antimicrobial therapy with agents
active against S. aureus and gram-negative rods. The fluoroquinolones, by virtue of their oral administration and antibacterial spectrum, may appropriately be used in some cases;
Clinical cures have been as high as 75% in chronic osteomyelitis in which gram-negative
rods predominated. Failures have been associated with the development of resistance in S. aureus, P. aeruginosa, and Serratia marcescens. In diabetic foot infections, which commonly are polymicrobial, the fluoroquinolones in combination with an agent with antianaerobic activity are a reasonable choice.

Other Infections
Ciprofloxacin received wide usage for the prophylaxis of anthrax and is effective for the treatment of tularemia. The quinolones may be used as part of multiple-drug regimens for the treatment of multidrug-resistant tuberculosis and for the treatment of atypical mycobacterial infections and Mycobacterium avium complex infections in AIDS.

Adverse Effects

1. The most common adverse reactions involve the GI tract, with 3–17% of patients reporting mostly mild nausea, vomiting, and/or abdominal discomfort. Diarrhea and antibiotic-associated colitis have been unusual.

2. CNS side effects, predominately mild headache and dizziness, have been seenin 1–10% of patients. Rarely, hallucinations, delirium, and seizures have occurred, predominantly in patients who also were receiving theophylline or a nonsteroidal anti-inflammatory drug.
Ciprofloxacin and pefloxacin inhibit the metabolism of theophylline and may induce toxic levels.
Nonsteroidal anti-inflammatory drugs may augment displacement of g-aminobutyric acid (GABA) from its receptors by the quinolones.

3. Rashes, including photosensitivity reactions, also can occur.

4. Leukopenia, eosinophilia, and mild elevations in serum transaminases occur rarely.

5. Prolongation of the QTc interval has been observed with sparfloxacin and to a lesser extent with gatifloxacin and moxifloxacin. Quinolones probably should be used only with caution in patients who are taking certain antiarrhythmics, including amiodarone, quinidine, and procainamide. The prescribing information for gatifloxacin includes a contraindication in diabetic patients due to serious reports of hypoglycemia and hyperglycemia. Risk factors for this adverse effect include older age, renal insufficiency, and concomitant therapy with glucose-altering medications.

6. Damage to motor nerves may produce the following symptoms:

  • Weakness
  • Muscle atrophy
  • Twitching, also known as fasciculation
  • Paralysis (palsy)

7. Sensory nerve damage may produce the following symptoms:

  • Pain
  • Sensitivity
  • Numbness
  • Tingling or prickling
  • Burning
  • Problems with positional awareness

Quinolones And Tendons Damage

Achilles tendon rupture or tendinitis are a rare adverse effect. Renal disease, hemodialysis, and glucocorticoid use may be predisposing factors. Traditionally, the use of quinolones in children has been contraindicated because they have produced arthropathy in animal models. However, children with cystic fibrosis given ciprofloxacin, norfloxacin, and nalidixic acid have had few, and reversible, joint symptoms.

Fluoroquinolone-associated bilateral patellar tendon rupture: a case report and review of the literature. 2010

Tendinopathy resulting from the use of fluoroquinolones: managing risks.2010

Levofloxacin-induced Achilles tendinitis in a young adult in the absence of predisposing conditions.2011

Spontaneous tendon ruptures in patients with end-stage renal disease.2009

Why The Use Of Quinolones Can Create A Tendon Damage?
It’s not clear the mechanism involved in tendons damage by quinolones, there are some studies that prove to explain this rare adverse effect:

Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen.2011

Metalloproteinases (or metalloproteases) constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc, some use cobalt. The metal ion is coordinated to the protein via three ligands. The ligands co-ordinating the metal ion can vary with histidine, glutamate, aspartate, lysine and arginine all possible ligands. The fourth coordination position is taken up by a labile water molecule.

Possible involvement of DEC1 on the adverse effects of quinolone antibiotics.2010

Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is an important transcription factor that has a basic helix-loop-helix domain and is ubiquitously expressed in both human embryonic and adult tissues, has a pivotal function in various biological phenomena, including neurogenesis, neuroregulation, chondrogenesis, cell growth, oncogenesis, immune balance and circandian rhythm.

Ciprofloxacin-mediated inhibition of tenocyte migration and down-regulation of focal adhesion kinase phosphorylation.2009

Age-dependent effects on redox status, oxidative stress, mitochondrial activity and toxicity induced by fluoroquinolones on primary cultures of rabbit tendon cells.2006

Is there a way to prevent the possible negative effect quinolones-induced on tendons?

The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells. 2009

MitoQ--a mitochondria-targeted antioxidant.2007

MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10, but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.

Are There Studies In Which Is Shown The Efficacy Of MitoQ Against Pathological Situations Induced By Ossidative Stress?

Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy.2009

The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis.2008

Animal and human studies with the mitochondria-targeted antioxidant MitoQ.2010

2015-01-20T11:26:38 - Gianpiero Pescarmona

Ascorbic Acid and ROS production


Divicine can transfer electrons from ascorbic acid to O2 producing Hydrogen Peroxide (H2O2)

Effect of divicine and isouramil on red cell metabolism in normal and G6PD-deficient (Mediterranean variant) subjects. Possible role in the genesis of favism. 1981

Fava beans contain high amounts (up to 6.7 g/100 g dry weight) vicine and convicine. Their active aglycones divicine and isouramil have equivalent metabolic effects. They rapidly oxidize GSH to GSSG in normal and G6PD-deficient red cells. No regeneration of GSH occurs in deficient cells. The stoichiometry of the divicine oxidation of GSH is 1:1. Ascorbic acid is quickly oxidized by isouramil in both normal and deficient cells but regenerates only in normal cells. Isouramil oxidizes NADH at a much lesser extent than NADPH. Glycolysis is activated at the glyceraldehyde 3-phosphate dehydrogenase step. Divicine strongly stimulates hexone monophosphate shunt only in normal red cells. Divicine alone or associated with ascorbic acid has almost no effect in deficient red cells. Malonyl dialdehyde production is slight and virtually the same in normal and deficient cells treated with 5 mM isouramil. Large polypeptide aggregates are formed after 12 and 24 hours incubation with 1 mM divicine in deficient cells only. Divicine (0.25 mM) markedly decreases the filterability of deficient cells. The results are consistent with a causal role of divicine/isouramil in the genesis of the hemolytic crisis occurring in G6PD-deficient subjects after fava bean ingestion.


Aminopyrimidoisoquinolinequinone (APIQ) redox cycling is potentiated by ascorbate and induces oxidative stress leading to necrotic-like cancer cell death. 2011

Taken together, our results show that ascorbate enhances quinone redox-cycling and leads to ROS formation that inhibits cell proliferation and provokes caspase-independent cell death.

An in vitro comparative study with furyl-1,4-quinones endowed with anticancer activities. 2010 Fulltext

A first group, which caused a severe decrease in the intracellular ATP content, is represented by the dimethylhydrazonofuryl-bearing naph- toquinones 1 and 2 which decreased ATP by 70% and 82%, respectively. A second group, composed of the benzoqui- nones 3 and 6, decreased ATP by nearly 40%. Finally, within the formylfuryl-bearing naphtoquinone group, a minor effect on ATP was observed: 5 decreased ATP by only 32%, while 4 had no effect on ATP content. For the second selected metabolic marker, namely the level of GSH, the situation was rather different to that observed for ATP and more closely resembled the effect observed on membrane cell lysis (Fig. 2). Indeed, almost all the quinone compounds decreased the level of GSH by approximately 30-40%.

NADPH oxidase activation

Activation of phagocytic cell NADPH oxidase by norfloxacin: a potential mechanism to explain its bactericidal action. 2002
El Bekay R1, Alvarez M, Carballo M, Martín-Nieto J, Monteseirín J, Pintado E, Bedoya FJ, Sobrino F.
Author information
* Abstract
The mechanisms underlying the bactericidal power of fluoroquinolones against intracellular parasites in host macrophages remain poorly understood. We have analyzed the effect of norfloxacin, a fluoroquinolone antibiotic, on the production of reactive oxygen intermediates (O(2)(*-) and H(2)O(2)) and NADPH oxidase activity in mouse macrophages. The generation of anion superoxide (O(2)(*-)) was found to be significantly greater in macrophages incubated with norfloxacin than in untreated controls. This enhancing effect of norfloxacin was dose-dependent and reached maximal values within 10 min after its addition. The O(2)(*-) generated was mainly intracellular, as determined by the use of specific dyes, such as lucigenin and luminol, and able to diffuse freely through the cell membrane. Also, the production of H(2)O(2) was increased in macrophages in response to norfloxacin. The positive effect of norfloxacin was associated to an enhanced mobilization of NADPH oxidase subunits p47(phox) and p67(phox) from the cytosol to the plasma membrane in phagocytic cells. The effect of the antibiotic persisted in vivo for several hours. These data support the notion that norfloxacin inhibits mycobacterial growth within phagocytic cells by enhancing intracellular production of O(2)(*-) and other reactive oxygen species.

2014-12-04T15:11:23 - Gianpiero Pescarmona

Impairment of Thyroid Hormones function

Ciprofloxacin interacts with thyroid replacement therapy. 2005

Ciprofloxacin impairs TH uptake by the cells

Quante persone hanno un TSH piu' alto dopo Chinolonici?

2014-12-01T15:02:01 - Andrea Favero

In merito alla deplezione muscolare che si verifica in alcuni casi seri di tossicità da fluorochinoloni, sembrerebbe che questo sia causato da piu' cause:

  • patologie che coinvolgono il sistema nervoso periferico contribuendo all'atrofia dei muscoli
  • la condizione di costante acidosi causata dal malfunzionamento dei mitocondri danneggiati dai FQ con diminuita produzione di CO2 e aumento di acido lattico (misurabile)
    • Diurnal hormone-metabolite profiles in hypothyroidism. 1981
      Fasting blood lactate and pyruvate levels were normal but post-prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1.80 +/- 0.06 v. control 0.77 +/- 0.03 mmol/l, P less than 0.01) and pyruvate (0.10 +/- 0.01 v. 0.08 +/- 0.003 mmol/l, P less than 0.01) were elevated.

(per il meccanismo che potrebbe essere spiegato dalla prima parte di questo video; che mi sembra dubbio GP)

2014-11-19T10:29:39 - Gianpiero Pescarmona

Discussione di un caso clinico

Maschio sano, anni 28
A causa di una sospetta cistite mi è stato prescritto dal medico curante il Ciproxin. A circa 20 ore dall’assunzione della prima compressa ho iniziato ad avvertire dolore al tendine d’Achille sinistro, poco dopo anche a quello destro. Mi sono recato quindi da uno specialista urologo che in seguito alla mia richiesta di un farmaco meno aggressivo per i tendini e mi ha prescritto il Tavanic (Levofloxacina) con l’aggiunta di un corticosteroide.
Il terzo giorno, dopo quindi due sole compresse, non riuscivo più a camminare a causa del dolore ai tendini d’Achille, talloni e ginocchia.
95% sintomi motori
5% sintomi sensitivi

Nonostante l’assunzione del farmaco sia stata interrotta, l’infiammazione ai tendini si è estesa in una settimana a tutto il corpo. A distanza di tre mesi qualsiasi movimento ripetitivo mi causa dolore e la forza che riesco ad esercitare nei movimenti è scarsissima. Mi è stata diagnosticata inoltre una neuropatia periferica sensitivo-motoria agli arti inferiori, pertanto la atrofia muscolare è stata notevolmente ridotta rendendomi difficili anche i più brevi spostamenti e precludendomi la possibilità di guidare o fare scale.

quinolones toxicity dexamethasone

Synergistic effects of dexamethasone and quinolones on human-derived tendon cells. 2010

Combined exposure to quinolones and dexamethasone led to more pronounced effects in tenocyte cultures at most of the analysed endpoints.


Perche' inibiscono l'azione della 1,25(OH)Vit D?

Ipotesi di lavoro

Assumiamo che i Chinolonici danneggino il mitocondrio riducendone la capacita' respiratoria e quindi la sintesi di ATP

  • Calcium Signals Are Affected by Ciprofloxacin as a Consequence of Reduction of Mitochondrial DNA Content in Jurkat Cells, 2006
    The effects of ciprofloxacin on mitochondrial DNA (mtDNA) content, oxygen consumption, mitochondrial membrane potential, cellular ATP formation, and capacitative Ca2+ entry into Jurkat cells were investigated. In cells incubated for several days with 25 μg/ml ciprofloxacin, a 60% reduction of mtDNA content, inhibition of the respiratory chain, and a significant decrease in mitochondrial membrane potential were observed. These changes led to a decrease in the calcium buffering capacity of mitochondria which, in turn, resulted in a gradual inhibition of the capacitative Ca2+ entry. On days 4, 7, and 11 of incubation with ciprofloxacin, the initial rates of Ca2+ entry were reduced by 33%, 50%, and 50%, respectively. Ciprofloxacin caused a transient decrease in the cellular capability for ATP formation. In cells incubated for 15 min with glucose, pyruvate, and glutamine as exogenous fuel, ciprofloxacin reduced ATP content by 16% and 35% on days 4 and 7, respectively, of incubation with the drug. However, on day 11 of incubation with ciprofloxacin, a recovery of cellular ATP formation was observed. In conclusion, long-term exposure of Jurkat cells to ciprofloxacin at a concentration of 25 μg/ml seriously affects cellular energy metabolism and calcium homeostasis.

per capire perche' alcuni soggetti presentino sintomi bisogna conoscere tutte i possibili fattori da cui dipende la produzione di ATP a livello mitocondriale.

Lo stesso ragionamento e' gia' stato applicato ai dolori muscolo/articolari

Sintesi di ATP

  • glucose
    • muscle
      • blood glucose
      • insulin
    • nerve
      • blood glucose
      • serum sodium
  • fatty acids
    • muscle
      • adrenaline ??
      • carnitine
  • anemia
  • smoking
  • BPCO




  • Serum Calcium
    • Calcium deficiency
      • low 25(OH)Vit D (its synthesis depends on mitochondrial respiration)
      • low calcium intake
  • Acetylcholine
  • Arginine
  • eNOS (endothelial nitric oxide synthase)
  • Calcium deficiency
    • 25(OH)Vit D (its synthesis depends on mitochondrial respiration)


Drugs Affecting Quinolones Pharmacokinetic

2011-04-29T08:58:05 - Paolo Pescarmona

CPK aumenta con statine

fluoroquinolone toxicity

quinolones mitochondria

Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway. 2008

  • Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk.

In merito alla sindrome di tossicità da fluorochinoloni, la reazione avversa a questi farmaci, quando si presenta nel modo più grave, sembra avere in comune sempre lo stesso schema: Infiammazione e/o degenerazione tendinea a distanza di pochi giorni dalla prima compressa assunta e danni al sistema nervoso periferico con conseguente atrofia muscolare di carattere esteso e visibile dopo pochi mesi.
Possono manifestarsi anche casi di neurotossicità a carico delle fibre minori con conseguente alterazioni delle sensazioni caldo/freddo, bruciori, pizzicore, scariche elettriche, etc...

Generalmente la sindrome migliora molto lentamente, con una remissione dei sintomi del 70% circa in 2-5 anni.
Purtroppo in alcuni casi i danni a carico del sistema nervoso risultano essere anche permanenti (come riportato anche in questo articolo) e stranamente non risultano essere dose-dipendenti secondo le centinaia di casi discussi fin'ora nei gruppi di discussione.

Osservando gli studi disponibili in letteratura, i meccanismi per cui questa tossicità si presenta sembrano essere i seguenti:

  • Deplezione del magnesio con conseguente indebolimento della struttura dei tendini
  • Citotossicità e neurotossicità da parte della struttura molecolare del chinolone e in particolar modo dell'atomo di fluoro che rende possibile una maggior penetrazione della molecola all'interno dei tessuti con conseguente necrosi cellulare più o meno generalizzata e possibile deplezione della mielina.
  • Inibizione dei recettori GABA grazie alla loro affinità chimica con la maggior parte delle molecole appartenenti alla famiglia dei fluorochinoloni.
    Deplezione del DNA mitocondriale attraverso l'inibilzione delle topoisomerasi e alterazione della permeabilità delle pareti dei mitocondri.

Tutto questo però non giustifica come mai la reazione avversa si presenti solo in alcuni rari casi (1-5%); si ritiene vi possano essere delle motivazioni dettate dal proprio patrimonio genetico tali da rendere più difficile da metabolizzare il farmaco giustificando quindi la maggiore tossicità individuale.

Influence of ciprofloxacin on leukotriene generation from various cells in vitro. 1990

  • The effect of ciprofloxacin on leukotriene generation from human polymorphonuclear leucocytes (PMN) and the respective lymphocyte, monocyte and basophil (LMB) containing cell fraction has been studied. Furthermore, the influence on the LTB4-receptor expression of PMNL, as well as on the synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) from human platelets, was analysed. The antibiotic concentrations ranged from 0.5 to 4 micrograms/10(7) cells. Analysis of the generated leukotrienes was performed by high performance liquid chromatography (HPLC). The calcium-ionophore A23187 induced leukotriene generation from PMNs and LMBs was significantly suppressed by preincubation with ciprofloxacin in a dose-dependent manner. Incubation of PMNs with the same concentrations of ciprofloxacin induced an augmentation of the LTB4-receptor expression. Preincubation of human platelets led to a suppression of the calcium-ionophore induced 12-HETE generation at high concentrations (8 and 4 micrograms/10(8) cells) and* to an increased synthesis of 12-HETE at lower concentrations (0.5, 1, and 2 micrograms ciprofloxacin/1 × 10(8) platelets)*.

Miscellaneous. 2008

Administration with metformin (150 mg / kg, p.o.), a widely used oral hypoglycemic agent, to diabetic animals further reduced circulating thyroid hormones and caused drug-induced hypothyroidism.


Role of mitochondria in ciprofloxacin induced apoptosis in bladder cancer cells. 2002

Cyclosporin A, a known inhibitor of the mitochondrial permeability transition pore, protected cells against decreased mitochondrial potential.

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