Study of hepatotoxins influence in vitro on basic biochemical indicators of liver functional state

An antimicrobial drug of the fluoroquinolone group, ciprofloxacin, is widely used in Ukraine. However, some researchers have noted the probable hepatotoxicity of this drug with prolonged use or use of high doses of ciprofloxacin. The aim of this study was to compare the effects of carbon tetrachloride, as a classical model of hepatocyte injury, with the effects of ciprofloxacin. The aim of the study was to investigate the biochemical parameters of the liver when simulating toxic damage to hepatocytes with carbon tetrachloride or ciprofloxacin. Materials and methods. The study was carried out on isolated rat hepatocytes, in whose culture medium carbon tetrachloride or ciprofloxacin was added. After incubation in the supernatant and cell homogenate, the activities of marker enzymes of cytolysis were determined: ALT, AST, γ-GTP, LF, LDH, DC and MDA. Results. The introduction of ciprofloxacin into the culture of hepatocytes at a concentration of LC50 caused changes in biochemical parameters similar to those caused by carbon tetrachloride. Thus, an increase in ALT, AST, γ-GTP, LF, LDH, DC and MDA was observed when CCl4 or ciprofloxacin was added to the culture. Conclusion. Incubation of rat hepatocytes with carbon tetrachloride or ciprofloxacin caused an increase in the level of enzymes and lipid peroxidation products. These parameters are indicators of gross changes in cells, which are the result of impaired keto acid formation, impaired redox reactions, impaired glycogen production

Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis

Background Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M. pneumoniae (MRMP) strains have become more common. In this study, we assessed the efficacy of tetracyclines and fluoroquinolones in MRMP treatment in children through a systematic review and meta-analysis. Methods Two reviewers individually searched 10 electronic databases (Medline/Pubmed, Embase, the Cochrane Library, and core Korean, Chinese, and Japanese journals) for papers published from January 1, 1990 to March 8, 2018. The following data for each treatment group were extracted from the selected studies: intervention (tetracyclines and fluoroquinolones/comparator), patient characteristics (age and sex), and outcomes (fever duration, hospital stay length, treatment success rate, and defervescence rates 24, 48, and 72 h after starting treatment). Results Eight studies involving 537 participants were included. Fever duration and hospital stay length were shorter in the tetracycline group than in the macrolide group (weighted mean difference [WMD] = − 1.45, 95% confidence interval [CI]: − 2.55 to − 0.36, P = 0.009; and WMD = − 3.33, 95% CI: − 4.32 to − 2.35, P < 0.00001, respectively). The therapeutic efficacy was significantly higher in the tetracycline group than in the macrolide group (odds ratio [OR]: 8.80, 95% CI: 3.12–24.82). With regard to defervescence rate, patients in the tetracycline group showed significant improvement compared to those in the macrolide group (defervescence rate after 24 h, OR: 5.34, 95% CI: 1.81–15.75; after 48 h, OR 18.37, 95% CI: 8.87–38.03; and after 72 h, OR: 40.77, 95% CI: 6.15–270.12). There were no differences in fever improvement within 24 h in patients in the fluoroquinolone group compared to those in the macrolide group (OR: 1.11, 95% CI: 0.25–5.00), although the defervescence rate was higher after 48 h in the fluoroquinolone group (OR: 2.78, 95% CI: 1.41–5.51). Conclusion Tetracyclines may shorten fever duration and hospital stay length in patients with MRMP infection. Fluoroquinolones may achieve defervescence within 48 h in patients with MRMP infection. However, these results should be carefully interpreted as only a small number of studies were included, and they were heterogeneous.

Development of Lipomer Nanoparticles for the Enhancement of Drug Release, Anti-Microbial Activity and Bioavailability of Delafloxacin

Delafloxacin (DFL) is a novel potent and broad-spectrum fluoroquinolone group of antibiotics effective against both Gram-positive and negative aerobic and anaerobic bacteria. In this study, DFL-loaded stearic acid (lipid) chitosan (polymer) hybrid nanoparticles (L-P-NPs) have been developed by single-emulsion-solvent evaporation technique. The mean particle size and polydispersity index (PDI) of optimized DFL-loaded L-P-NPs (F1-F3) were measured in the range of 299–368 nm and 0.215–0.269, respectively. The drug encapsulation efficiency (EE%) and loading capacity (LC%) of DFL-loaded L-P-NPs (F1-F3) were measured in the range of 64.9–80.4% and 1.7–3.8%, respectively. A sustained release of DFL was observed from optimized DFL-loaded L-P-NPs (F3). Minimum inhibitory concentration (MIC) values of the DFL-loaded L-P-NPs (F3) appeared typically to be four-fold lower than those of delafloxacin in the case of Gram-positive strains and was 2-4-fold more potent than those of delafloxacin against Gram-negative strains. The pharmacokinetic study in rats confirmed that the bioavailability (both rate and extent of absorption) of DFL-loaded L-P-NPs was significantly higher (2.3-fold) than the delafloxacin normal suspension. These results concluded that the newly optimized DFL-loaded L-P-NPs were more potent against both Gram-positive and negative strains of bacteria and highly bioavailable in comparison to delafloxacin normal suspension.

Topical ciprofloxacin induced ocular toxicity: case report

Ciprofloxacin is a commonly used fluoroquinolone group of antimicrobial which is used for treating infective conditions like community acquired pneumonia and urinary tract infections. A patient of cataract was treated with ciprofloxacin eye drop as her pre-operative medication. She presented after four days with itching and redness in her right eye with swelling of the peri-orbital skin. We report this rare case where topical application of ciprofloxacin was responsible for the ocular symptoms.

Use of fluoroquinolones in practice of veterinary medicine of Ukraine

Antibacterial agents are one of the most important groups of medical preparations in the treatment of bacterial infection of different localization in humane and in veterinary medicine. The consequence of their rational use (the establishment of sensitivity of the pathogenic microflora, compliance with the course of treatment, etc.) have a high therapeutic effect and the minimum development of resistant strains of microorganisms. The widely used group of antimicrobial agents in veterinary medicine are second-generation fluorohinolone antibiotics that have good pharmacokinetic properties, a broad spectrum of bactericidal activity, and relatively low toxicity, although they have their own warnings and restrictions on the use of small animals during the formation of bone tissue. To achieve high therapeutic efficacy and minimizing of side effects, it is described the compatibility of some fluoroquinolones with other pharmacological groups. They found their application in the treatment of both productive animals, poultry, fur animals and petty domestic (dogs and cats) with a bacterial infection of the urinary tract, digestive and respiratory systems, infected wounds, etc. The article describes the detailed mechanism of action of the antibiotics of the fluoroquinolone group, which provides an opportunity for a deeper understanding of the manifestation of the bactericidal effect, as well as their classification by generation or generation. Particular attention deserves attention to the time of carrenia of fluoroquinolones in the context of their application to productive animals, because high quality livestock products minimize the development of resistant strains in humans and provide them with health. There is also a list of all registered medicinal products registered in Ukraine containing: ofloxacin, enrofloxacin, ciprofloxacin, marbofloxacin, denofloxacin, which carries important informative information for practicing doctors, pharmacists, etc.

Residue Depletion Study of Danofloxacin in Cultured Tilapia (Oreochromis mossambicus)

Danofloxacin is an antibacterial drug of the fluoroquinolone group developed for therapeutic purposes in veterinary medicine. The studies described here include investigations of the residues following a single dose or multiple doses of danofloxacin. Residue depletion studies were performed to determine residues in plasma and tissues of saltwater tilapia fish (Oreochromis mossambicus) after a single oral administration of danofloxacin at the dose of 10 mg/kg body weight and also after daily dose of 10 mg/kg body weight for five consecutive days. Danofloxacin residues were analyzed by HPLC with fluorescence detection. Following a single oral dose, danofloxacin residues in 6 h postdosing tilapia were at a maximum of 1.44, 12.48, and 13.18 μg/g in serum, liver, and kidney samples, respectively, while a peak muscle concentration of 2.15 μg/g was reached at 12 h. From single-dose data, the concentration of danofloxacin in serum, muscle, liver, and kidney samples declined with half-lives of 29, 34, 49, and 44 h, respectively. Based on the maximum residue level (MRL) of 0.1 μg/g in edible tissue for fin fish, the withdrawal times of danofloxacin in muscle were estimated to fall below the MRL after a withdrawal period of 21 days following the multiple-dose administration. These results may be helpful to regulatory agencies as they determine what tissues should be monitored to ensure that the established residue safety tolerance levels are not exceeded.

Susceptibility Pattern of Gram Negative Urine Pathogens with Exclusion of Escherichia coli to Quinolone/ Fluoroquinolone Antibiotics

Quinolone/Fluoroquinolones group of antibiotics are frequently used for the treatment of urinary tract infection (UTI). Because of high frequency of Gram negative bacterial infection in UTI and emerging resistant urinary pathogen in spite of lower prevalence with exclusion of Escherichia coli, the susceptibility pattern was subjected in this study. The study was conducted at National Public Health Laboratory (NPHL) Teku, Kathmandu with an objective to study the antibiotic Quinolone/Fluoroquinolones susceptibility pattern. Out of 550 urine samples, 100 (18.18%) bacteria were isolated from NPHL. Also, 69 isolates from Blue-Cross Hospital and 83 isolates from Medicare Hospital were collected. Altogether 252 urine isolates, showing significant growth in MacConkey Agar and blood agar were identified by standard microbiological techniques. Among 62 Gram negative isolates other than Escherichia coli subjected for the study; Proteus mirabilis (27.42%), Proteus vulgaris (11.29%), Klebsiella oxytoca (12.90%), Klebsiella pneumoniae (17.75%), Citrobacter freundii (8.06%), Enteribacter cloaecae (6.45%), Pseudomonas aeruginosa (12.90%), Acinetobacter spp. (3.23%). Altogether eight types of antibiotics belonging to quinolone/fluoroquinolone group were used in this study. Among them, norfloxacin was found most sensitive and nalidixic acid was most resistant against Gram negative isolates.DOI: http://dx.doi.org/njst.v15i2.12119Nepal Journal of Science and Technology Vol. 15, No.2 (2014) 77-84

GAMBARAN HISTOPATOLOGI KARTILAGO SENDI LUTUT TIKUS WISTAR SETELAH PEMBERIAN SIPROFLOKSASIN

Ciprofloxacin is a kind of antibiotic which belongs to the fluoroquinolone group. It is very effective against microbes, but has several side effects in bones, joints, and tendons, especially for individuals under 18 years. The purpose of this study was to find out the side effects of ciprofloxacin on wistar rats’ knee joints. This was an experimental and descriptive study, using 12 wistar rats as samples, which were grouped in 4 groups: 3 treated, 1 control. The treated groups were given different total daily oral doses of ciprofloxacin (2 mg, 6 mg, and 18 mg) for 14 days. On the 15th day, all the samples were terminated, and their right back knees were examined pathologically, focusing on the knee cartilages. Wistar rats treated with 18 mg ciprofloxacin showed foci of cartilage matrix edema and degradation of chondrocytes. This study concluded that 18 mg doses of ciprofloxacin daily caused destruction of the matrix and chondrocytes of the wistar rats’ knee joint cartilages. Key words: ciprofloxasin, knee joint, matrix edema, chondrocytes’ degradation. Abstrak: Siprofloksasin adalah antibiotik golongan fluorokuinolon yang sangat efektif untuk mengobati infeksi, namun dapat menimbulkan beberapa efek samping, antara lain gangguan pada tulang, sendi, dan tendon, terutama pada yang berusia dibawah 18 tahun. Tujuan penelitian ini untuk mengetahui efek siprofloksasin pada sendi lutut tikus. Penelitian ini bersifat eksperimental deskriptif dengan menggunakan sampel 12 ekor tikus wistar yang dibagi atas empat kelompok (3 kelompok perlakuan dan 1 kelompok kontrol). Pada kelompok perlakuan diberikan siprofloksasin per oral dengan dosis 2mg, 6 mg, dan 18 mg setiap hari selama 14 hari. (Dosis ini pada manusia dengan berat badan rata rata 50 kg setara dengan dosis 1000 mg, 3000 mg, dan 9000 mg per hari). Pada hari ke15, tikus kontrol dan perlakuan diterminasi kemudian sendi lutut di eksisi dan dilakukan pemeriksaan histopatologi. Pemeriksaan histopatologi sendi lutut difokuskan pada jaringan kartilago hialin. Tikus kontrol dan tikus perlakuan dengan pemberian siprofloksasin dosis 2 mg dan 6 mg memperlihatkan jaringan kartilago normal; sedangkan pada tikus perlakuan dengan dosis 18 mg terlihat fokus-fokus pembengkakan matriks tulang rawan dan degradasi kondrosit. Dari hasil penelitian ini dapat disimpulkan bahwa pemberian siprofloksasin pada tikus wistar dengan dosis 18 mg (setara dengan 9000 mg pada manusia) per hari selama 14 hari telah menimbulkan kelainan fokal pada kartilago berupa pembengkakan matriks dan degradasi kondrosit. Kata kunci: siprofloksasin, sendi lutut, pembengkakan matriks, degradasi kondrosit.