Mechanisms of hormetic effects of ofloxacin on Chlorella pyrenoidosa under environmental-relevant concentration and long-term exposure.

Antibiotics are frequently detected in surface water and pose potential threats to organisms in aquatic ecosystem such as microalgae. The occurrence of biphasic dose responses raised the possibility of stimulation of microalgal biomass by antibiotics at environmental-relevant concentration and caused potential ecological risk such as algal bloom. However, the underlying mechanisms of low concentration-induced hormetic effects are not well understood. In this study, we evaluated the hormesis of ofloxacin on Chlorella pyrenoidosa under environmental-relevant concentration and long-term exposure. Results showed the hormetic effects of ofloxacin on cell density and carbon fixation rate (RC). The predicted maximum promotion was 17.45 % by 16.84 µg/L and 20.08 % by 15.78 µg/L at 21 d, respectively. The predicted maximum concentration of non-effect on cell density and RC at 21 d was 3.24 mg/L and 1.44 mg/L, respectively. Ofloxacin induced the mobilization of pigments and antioxidant enzymes to deal with oxidative stress. PCA analysis revealed Chl-a/Chl-b could act as a more sensitive biomarker under acute exposure while chlorophyll fluorescence parameters were in favor of monitoring long-term implication. The hormesis in increased secretion of extracellular organic matters was regarded as a defensive mechanism and accelerated indirect photodegradation of ofloxacin. Bioremoval was dominant and related to biomass accumulation in the total dissipation while abiotic removal appeared slight contributions. This study provided new insights into the understanding of hormesis of microalgae induced by antibiotics.

An optimized electro-fenton pretreatment for the degradation and mineralization of a mixture of ofloxacin, norfloxacin, and ciprofloxacin.

The electro-Fenton process (EFP) is a powerful advanced oxidation process beneficial to treating recalcitrant contaminants, and there has been a continuing interest in combining this technology to enhance the efficiency of conventional wastewater treatment processes. In this work, an optimized EFP process is performed as pretreatment for the degradation and mineralization of three blank fluoroquinolones (FQs) drugs: ofloxacin (OFL), norfloxacin (NOR), and ciprofloxacin (CIP). The optimization of the experiment was carried out using a Box-Behnken experimental design. Faster and complete degradation of the drugs mixture was achieved in 90 min with 61.12 ± 2.0% of mineralization in 180 min, under the optimized conditions: j = 244.0 mA cm-2, [Fe2+] = 0.31 mM, and [FQs] = 87.0 mg L-1. Furthermore, a low toxicity effluent was obtained in 90 min of the experiment, according to bioassay toxicity with Vibrio fischeri. Five short-chain carboxylic acids, including oxalic, maleic, oxamic, formic, and fumaric acids, were detected and quantified, in addition to F- and NO3- inorganic ions. The inhibition of the reactive oxygen species with scavenger proof was also evaluated in this paper.

The co-presence of polystyrene nanoplastics and ofloxacin demonstrates combined effects on the structure, assembly, and metabolic activities of marine microbial community.

Nanoplastic is increasing in environments and can address toxic effects on various organisms. Particle size, concentration, and surface functionalization most influence nanoplastic toxicity. Besides, nanoplastic can adsorb other contaminants (e.g., antibiotics) to aggravate its adverse effects. The combined effects of nanoplastics and antibiotics on planktonic/benthic microbial communities, however, are still largely unknown. In this study, the combined effects of polystyrene nanoplastic and ofloxacin on the structure, assembly, and metabolic activities of marine microbial communities were investigated based on amplicon sequencing data. The results mainly demonstrate that: (1) nanoplastic and ofloxacin have greater impacts on prokaryotic communities than eukaryotic ones; (2) niche breadths of planktonic prokaryotes and benthic eukaryotes were shrank with both high nanoplastic and ofloxacin concentrations; (3) increased ofloxacin mainly reduces nodes/edges of co-occurrence networks, while nanoplastic centralizes network modularity; (4) increased nanoplastic under high ofloxacin concentration induces more differential prokaryotic pathways in planktonic communities, while benthic communities are less influenced. The present work indicates that co-presence of nanoplastics and ofloxacin has synergistic combined effects on community structure shifts, niche breadth shrinking, network simplifying, and differential prokaryotic pathways inducing in marine microbial communities, suggesting nanoplastics and its combined impacts with other pollutions should be paid with more concerns.

Study effect and mechanism of ofloxacin and levofloxacin on development of Rana nigromaculata tadpoles based on the hypothalamus-pituitary-thyroid axis.

Excessive antibiotics transferred into the aquatic environment may affect the development of amphibians. Previous studies on the aquatic ecological risk of ofloxacin generally ignored its enantiomers. The purpose of this study was to compare the effects and mechanisms of ofloxacin (OFL) and levofloxacin (LEV) on the early development of Rana nigromaculata. After 28-day exposure at environmental levels, we found that LEV exerted more severe inhibitory effects on the development of tadpoles than OFL. According to the enrichment results of differentially expressed genes in the LEV and OFL treatments, LEV and OFL had different effects on the thyroid development of tadpoles. dio2 and trh were affected by the regulation of dexofloxacin instead of LEV. At the protein level, LEV was the main component that affected thyroid development-related protein, while dexofloxacin in OFL had little effect on thyroid development. Furthermore, molecular docking results further confirmed that LEV was a major component affecting thyroid development-related proteins, including DIO and TSH. In summary, OFL and LEV regulated the thyroid axis by differential binding to DIO and TSH proteins, thereby exerting differential effects on the thyroid development of tadpoles. Our research is of great significance for comprehensive assessment of chiral antibiotics aquatic ecological risk.

Responses of cyanobacterium Microcystis aeruginosa under single and repeated ofloxacin exposure.

Antibiotics are omnipresent and pseudo-persistent in the environment. Yet, their potential ecological risks under repeated exposure, which is more environmentally relevant, are understudied. Therefore, this study used ofloxacin (OFL) as the probe chemical to investigate the toxic effects of different exposure scenarios-single dose of high concentration (4.0 µg/L) and multiple additions of low concentrations-towards the cyanobacterium Microcystis aeruginosa. Flow cytometry was employed to measure a collection of biomarkers, including endpoints related with biomass, single cell properties and physiological status. Results showed that the single dose of the highest OFL level inhibited cellular growth, chl-a content and cell size of M. aeruginosa. In contrast, OFL induced stronger chl-a autofluorescence and higher doses tended to have more remarkable effects. Repeated low OFL doses can more significantly increase the metabolic activity of M. aeruginosa than a single high dose. Viability and cytoplasmic membrane were not affected by OFL exposure. Oxidative stress was observed for the different exposure scenarios, with fluctuating responses. This study demonstrated the different physiological responses of M. aeruginosa under different OFL exposure scenarios, providing novel insights into the toxicity of antibiotics under repeated exposure.

Hydroxyl radicals can significantly influence the toxicity of ofloxacin transformation products during ozonation.

Ozonation is often applied to eliminate the recalcitrant contaminants in water. During the process, toxic transformation products (TPs) can be generated mainly via the reactions with ozone and hydroxyl radicals (•OH). However, the toxicity difference between the TPs generated from O3 and •OH has not been well elucidated. In this study, we designed ozonation scenarios with different Rct values (the exposure ratio of •OH to O3) via varying pH values, adding a catalyst or a radical scavenger, and investigated the degradation of a popularly used antibiotic ofloxacin (OFX). The microbial oxygen uptake, the development of zebrafish embryos, and the calculation with the Toxicity Estimation Software Tool (T.E.S.T) were applied to evaluate the toxicity of TPs generated from the above reaction scenarios. The toxicity tests demonstrated that TPs formed at high-Rct conditions were less toxic than those at low-Rct conditions. Ten and eleven TPs were identified during ozonation of OFX at pH 3 and 9, respectively, based on which the different pathways were proposed. The piperazine ring's demethylation and opening occurred at both pH values, while the hydroxylation of quinolone and oxazine mainly occurred at pH 9. The study suggests that •OH might be more efficient in eliminating the toxicity of OFX than O3.

Efficient ofloxacin degradation via photo-Fenton process over eco-friendly MIL-88A(Fe): Performance, degradation pathways, intermediate library establishment and toxicity evaluation.

The high-throughput production of the eco-friendly MIL-88A(Fe) was achieved under mild reaction conditions with normal pressure and temperature. The as-prepared MIL-88A(Fe) exhibited efficient photo-Fenton catalytic ofloxacin (OFL) degradation upon visible light irradiation with good stability and reusability. The OFL (20.0 mg/L) was completely degraded within 50 min under visible light with the aid of MIL-88A(Fe) (0.25 g/L) and H2O2 (1.0 mL/L) in aqueous solution (pH = 7.0). The hydroxyl radicals (·OH) are the main active species during the photo-Fenton oxidation process. Meanwhile, the degradation intermediates and the corresponding degradation pathways were identified and proposed with the aid of both ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and density functional theory (DFT) calculations. Finally, the degradation product library was firstly established to identify intermediate transformation products (TPs) with their variation of concentration, and their corresponding toxicologic activities were assessed via Toxtree and T.E.S.T software as well. Finally, the MIL-88A is efficient and stable with four cycles' catalysis operations, demonstrating good potential for water treatment.

Effects of ofloxacin on the structure and function of freshwater microbial communities.

Ofloxacin (OFL) is a broad-spectrum fluoroquinolone antibiotic frequently used in clinic for treating bacterial infections. The discharged OFL would inevitably enter into aquatic ecosystems, affecting the growth of non-target microorganisms, which may result in micro-ecosystem imbalance. To the best of our knowledge, researches in this area are rather sparse. The present study evaluated the response of photosynthetic microorganisms (cyanobacteria, eukaryotic algae) and aquatic microbial community to OFL in a microcosm. Results showed that ofloxacin presented an inhibitory effect on the growth Microcystis aeruginosa. Although 0.1 mg/L OFL has no significant impact on alpha diversity of the microbial communities, it obviously altered the structure and decreased the species interaction of prokaryotic community by reducing the capacities of nitrogen fixation, photosynthetic and metabolic capacity of the microbial community. This study pointed out that the residual OFL in water would disturb the balance of the aquatic micro-ecology, suggesting that more attentions should be given to the negative effects of antibiotics and other bioactive pollutants on aquatic environments.

Chronic ecotoxicology and statistical investigation of ciprofloxacin and ofloxacin to Daphnia magna under extendedly long-term exposure.

Ciprofloxacin (CFX) and ofloxacin (OFX) are two of the most often used fluoroquinolone antibiotics, and their residues are found in large amounts in various aquatic settings. However, the toxicity tests of CFX using eukaryotic organisms such as Daphnia magna are inadequate, and the test result of OFX is currently unknown. Therefore, the chronic toxicity test for D. magna was performed during 42 days under exposure to CFX and OFX concentrations of 50, 500, and 5000 µg L-1. All exposure conditions did not cause mortality for D. magna. CFX exposure at 500 µg L-1 resulted in an earlier oogenesis date and increased brood size in the second birth. The Poisson-based generalized linear mixed-effects model revealed that the reduction of fertility was statistically significant for the CFX and OFX exposures at 5000 µg L-1. On the other hand, the production of dead eggs as offspring degradation was also found significantly as maternal D. magna exposed to antibiotics at 5000 µg L-1. In addition, following long-term exposure to antibiotics, maternal adaptation to antibiotics was established for offspring deterioration and fertility. However, the OFX exposure showed that the fertility-suppressed effects continued for a longer period than the CFX exposure. Although no rational explanation has yet been given for the more substantial effect of OFX on reducing fertility than CFX, molecular cell biology and symbiotic microbial flora derived from previous studies could explain our ecotoxicological results. This study is the first report for the OFX chronic toxicities on D. magna by comparing it to the toxicity of CFX. Our study contributes to guiding the future impact assessment of fluoroquinolone antibiotic pollution on ecosystems, including the need for new statistical methods in ecotoxicological studies.

Grafting resulting in alleviating tomato plant oxidative damage caused by high levels of ofloxacin.

Antibiotic pollution has become a global problem threatening human health. Ofloxacin is one of the more widely used antibiotics, but reports on the reaction of plant to ofloxacin pollution are limited. In this study, using adversity-resistant (R), adversity-sensitive (S) and grafted plant S/R as models, we investigated the biological response of tomato to exogenous ofloxacin residues. The results showed that lower levels of ofloxacin treatment (5 mg L-1 and 10 mg L-1) promoted tomato growth, and 10 mg L-1 ofloxacin was the critical dose to stimulate growth among the different treatments. In addition, the photosynthetic and fluorescence parameters, antioxidant enzyme activities and transcription-level expression of the enzymes were stimulated by low ofloxacin treatment. However, high ofloxacin treatment (20 mg L-1 and 40 mg L-1) exhibited a significantly negative effect on plant growth, photosynthesis, fluorescence parameters, antioxidant enzyme activities and transcript levels expression. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels increased with increasing ofloxacin concentrations, indicating that the oxidative damage of plants was severe with increasing doses. In contrast, the role of antioxidant enzymes in the antibiotic response was limited at high ofloxacin concentrations. The grafting experiment demonstrated that grafted plants had the ability to alleviate ofloxacin stress. In conclusion, ofloxacin can damage the photosynthetic machinery by promoting ROS accumulation, which results in the etiolation of tomato leaves and inhibits plant growth, but grafting can reduce its.

Ofloxacin induces etiolation in Welsh onion leaves.

Antibiotic pollution has become an important global issue, and ofloxacin (OFL) is widely used worldwide. However, little is known about the potential adverse effects of OFL on plants. We assessed the toxic effects of OFL on Welsh onion and explored its toxicity mechanism. The leaf pigment content increased in 0.1 mg/L of OFL but decreased in a dose-dependent manner (0.5-2 mg/L OFL) until leaf etiolation. The ultrastructure of leaves showed that the treatment of 2 mg/L OFL produced significant toxicity. Furthermore, photosynthetic and fluorescence parameters were negatively affected by OFL treatment. The photosynthetic electron transport chain was significantly inhibited by OFL treatment, especially between QA and QB. The hydrogen peroxide and malondialdehyde content also increased with OFL concentration, indicating that antioxidant enzymes' role in antibiotic response is limited. In conclusion, OFL can damage chloroplasts by promoting ROS accumulation, which results in the etiolation of Welsh onion leaves.

Response of Cyperus involucratus to sulfamethoxazole and ofloxacin-contaminated environments: Growth physiology, transportation, and microbial community.

Plant-microbe is a complementary coupling system for antibiotics removing in constructed wetlands (CWs), but how plant and rhizosphere microbiomes respond to antibiotics exposure and the occurrence of ARGs in this microenvironment have seldom been researched. Thus, the response of the plant-microbe coupling system to different levels of antibiotics (sulfamethoxazole (SMZ) and ofloxacin (OFL)) was investigated. The results showed that two antibiotic stressors have hormetic effects on plant growth, physiology, and microbial community evolution, and the antibiotic toxic effects presented as SMZ + OFL > SMZ > OFL. Antibiotic accumulation in the plants was in the order of roots > stems > leaves. Notably, the root attachments affected antibiotic transportation. The accumulation of antibiotics in the under-ground parts affected the rhizosphere microbial community structure, and the microorganisms were more sensitive to SMZ + OFL than the plants, with inflection points of 0.5 mg L-1 and 1 mg L-1, respectively. Pseudomonas was highly resistant to antibiotics, while Acidovorax and Devosia may play a role in antibiotic degradation. Correlation analysis and network analysis showed that antibiotic enrichment and the bacterial community contributed significantly to the abundance of antibiotic-resistant genes (ARGs), further revealing the co-occurrence of int1, ARGs, and the potential bacterial hosts.

The tolerance mechanism and accumulation characteristics of Phragmites australis to sulfamethoxazole and ofloxacin.

Antibiotic pollution has become a hot issue worldwide, which has toxic effects on plants and even threatens human health. As a common wetland plant, the tolerance mechanism of Phragmites australis to antibiotics is rarely reported. In this study, we investigated the enrichment characteristics and biological response of P. australis to sulfamethoxazole (SMZ) and ofloxacin (OFL) residues, which are common in the environment. We found that the simulated concentration of antibiotics far exceeded the current level of antibiotic residues in the water environment, but it did not significantly inhibit the growth of P. australis. At 1 mg L-1, OFL and SMZ significantly increased the biomass of P. australis, which was mainly related to the improvement of root activity and photosynthetic efficiency, but the duplex treatment (SMZ + OFL) did not significantly stimulate the growth of reeds. OFL could significantly reduce the accumulation of reactive oxygen species (ROS) in P. australis. When OFL was 1 mg L-1, compared with control, superoxide anion and H2O2 were reduced by 11.19% and 10.76%, respectively, which was mainly related to the improvement of membrane stability. SMZ and SMZ + OFL had no significant effect on ROS, but they significantly increased antioxidant enzyme activity. SMZ and OFL could increase soil invertase, urease, and protease activities, and the tested antibiotics had no significant effect on the Shannon-Wiener index of soil microorganisms. The accumulation of antibiotics within tissues could be ranked as root > leaf > stem, and the accumulation and transport of OFL were higher than those of SMZ.

Influence of organic carbon fractions of freshwater biofilms on the sorption for phenanthrene and ofloxacin: The important role of aliphatic carbons.

Sorption to biofilms is thought to be a crucial process controlling the fate of trace organic contaminants in aquatic systems. The organic composition of biofilms is regarded as the determining factor in the sorption mechanism of biofilm organic carbon fractions; however, its role is not well known. Here, the sorption of phenanthrene and ofloxacin was modeled with classic and emerging organic contaminants, respectively, by comparatively investigating nine type of freshwater biofilms cultured in a river, lake, and reservoir in spring, summer, and autumn. The chemical features of the nine biofilms were analyzed using elemental analysis, infrared spectroscopy, X-ray photoelectron spectroscopy, and carbon-13 nuclear magnetic resonance. Results showed that the freshwater biofilms were aliphatic-rich natural amorphous solid substances with O-containing functional groups, and their surface polarity was significantly lower than their bulk polarity. All the isotherms of phenanthrene and ofloxacin sorption by the biofilms were linear. The organic carbon-normalized partition coefficient values for phenanthrene and ofloxacin on the nine biofilms ranged from 91.9 to 364.2 L g-1 and 3.2 to 43.2 L g-1, respectively. The van der Waals interaction between a majority of aliphatic carbon (73.4%-83.9%) in biofilms and the two sorbates was much stronger than π-π interactions between a minority of aromatic carbon (12.7%-21.7%) and sorbates. The surface polarity of the biofilms regulated polar interactions including the hydrogen bonding and electron donor-acceptor interactions. Both the aliphatic carbon and surface polarity in the biofilms enhanced the sorption of phenanthrene and ofloxacin. The sorption characteristics and mechanisms of polycyclic aromatic hydrocarbons and antibiotics on biofilms shown in our present and previous studies are different from those of other ubiquitous natural solid materials such as soils and sediments. This study provides insight into the importance of aliphatic carbon fractions of freshwater biofilms for the sorption of classic and emerging organic contaminants.

Biomarker Effects in Carassius auratus Exposure to Ofloxacin, Sulfamethoxazole and Ibuprofen.

Ofloxacin, sulfamethoxazole and ibuprofen are three commonly used drugs which can be detected in aquatic environments. To assess their ecotoxicity, the effects of these three pharmaceuticals and their mixture on AChE (acetylcholinesterase) activity in the brain, and EROD (7-ethoxyresorufin-O-deethylase) and SOD (superoxide dismutase) activities in the liver of the freshwater crucian carp Carassius auratus were tested after exposure for 1, 2, 4 and 7 days. The results showed that treatments with 0.002⁻0.01 mg/L ofloxacin and 0.0008⁻0.004 mg/L sulfamethoxazole did not significantly change AChE, EROD and SOD activities. AChE activity was significantly inhibited in response to treatment with 0.05mg/L ofloxacin and 0.02mg/L sulfamethoxazole. All three biomarkers were induced significantly in treatments with ibuprofen and the mixture of the three pharmaceuticals at all the tested concentrations. The combined effects of ofloxacin, sulfamethoxazole and ibuprofen were compared with their isolated effects on the three biomarkers, and the results indicated that exposure to ibuprofen and the mixture at environmentally relevant concentrations could trigger adverse impacts on Carassius auratus. The hazard quotient (HQ) index also demonstrated a high risk for ibuprofen. Moreover, the present study showed that the effects of ofloxacin, sulfamethoxazole and ibuprofen might be additive on the physiological indices of Carassius auratus.

Phytotoxicity and degradation of antibiotic ofloxacin in duckweed (Spirodela polyrhiza) system.

The phytotoxicity and degradation of ofloxacin (OFX) in duckweed Spirodela polyrhiza based system was estimated in this study. For that, OFX was added in an environmentally relevant range (0.01-1.0 mg L-1) in medium (Hoagland nutrient) and toxicity biomarkers, i.e. changes in plant biomass, relative growth rate (RGR), photopigment (Chl-a, Chl-b and carotenoids), protein content, antioxidative enzymes (catalase, CAT; superoxide dismutase, SOD; and ascorbate peroxidases, APX) in fronds were estimated. The batch-scale setups (250 ml) was prepared in triplicate for each concentration of OFX and reared in growth chambers (Algae Tron AG 230) for 7 d. Results suggested that the high concentrations of OFX caused a reduction in biomass (4.8-41.3%), relative root growth (RGR), protein (4.16-11.28%) and photopigment contents. The fronds in OFX spiked setups showed an increased level of antioxidative enzymes: CAT (0.230-0.338 mmolH2O2 mg-1 protein), APX (0.043-0.074 mmolascorbate mg-1 protein), and SOD (0.267-0.317 U mg-1 protein) than control. At the end (7 d), the residual OFX content in the medium was also estimated, and results suggested a significant (p < 0.05) reduction (93.73-98.36%) in OFX content than control setup (54.76-75.53%) at the end of the experimentation. The trend of residual OFX suggested phytodegradation as a significant mechanism of antibiotic degradation other than hydrolysis and photodegradation processes. This study indicates that duckweed can be an effective bio-tool for the removal of environmental relevant concentration of the antibiotics from the wastewater.

Response of Freshwater Biofilms to Antibiotic Florfenicol and Ofloxacin Stress: Role of Extracellular Polymeric Substances.

Antibiotic residues have been detected in aquatic environments worldwide. Biofilms are one of the most successful life forms, and as a result are ubiquitous in natural waters. However, the response mechanism of freshwater biofilms to the stress of various antibiotic residues is still unclear. Here, the stress of veterinary antibiotic florfenicol (FF) and fluoroquinolone antibiotic ofloxacin (OFL) on freshwater biofilms were investigated by determining the changes in the key physicochemical and biological properties of the biofilms. The results showed that the chlorophyll a content in biofilms firstly decreased to 46⁻71% and then recovered to original content under the stress of FF and OFL with high, mid, and low concentrations. Meanwhile, the activities of antioxidant enzymes, including superoxide dismutase and catalase, increased between 1.3⁻6.7 times their initial values. FF was more toxic to the biofilms than OFL. The distribution coefficients of FF and OFL binding in extracellular polymeric substances (EPS)-free biofilms were 3.2 and 6.5 times higher than those in intact biofilms, respectively. It indicated that EPS could inhibit the FF and OFL accumulation in biofilm cells. The present study shows that the EPS matrix, as the house of freshwater biofilms, is the primary barrier that resists the stress from antibiotic residues.

Lipid metabolism disorder induced by up-regulation of miR-125b and miR-144 following ß-diketone antibiotic exposure to F0-zebrafish (Danio rerio).

ß-Diketone antibiotics (DKAs) are widely used in human and veterinary medicine to prevent and treat a large variety of infectious diseases. Long-term DKA exposure to zebrafish can result in lipid metabolism disorders and liver function abnormalities. Based on our previous miRNA-seq analyses, miR-144 and miR-125b were identified as target genes regulating lipid metabolism. DKA-exposure at 12.5 and 25 mg/L significantly increased the expressions of miR-144 and miR-125b. The expression levels for the two miRNAs exhibited an inverse relationship with their lipid-metabolism-related target genes (ppardb, bcl2a, pparaa and pparda). Over-expression and inhibition of miR-144 and miR-125b were observed by micro-injection of agomir-144, agomir-125b, antagomir-144 and antagomir-125b. The over-expression of miR-144 and miR-125b enhanced lipid accumulation and further induced lipid-metabolism-disorder syndrome in F1-zebrafish. The expression of ppardb and bcl2a in whole-mount in situ hybridization was in general agreement with results from qRT-PCR and was concentration-dependent. Oil red O and H&E staining, as well as related physiological and biochemical indexes, showed that chronic DKA exposure resulted in lipid-metabolism-disorder in F0-adults, and in F1-larvae fat accumulation, increased lipid content, abnormal liver function and obesity. The abnormal levels of triglyceride (TG) and total cholesterol (TCH) in DKA-exposed zebrafish increased the risk of hyperlipidemia, atherosclerosis and coronary heart disease. These observations improve our understanding of mechanisms leading to liver disease from exposure to environmental pollution, thereby having relevant practical significance in health prevention, early intervention, and gene therapy for drug-induced diseases.

Studies on articular and general toxicity of orally administered ozenoxacin in juvenile rats and dogs.

AIM: Ozenoxacin is a nonfluorinated quinolone antibacterial approved for topical treatment of impetigo. Because quinolones have known chondrotoxic effects in juvenile animals, the potential toxicity of ozenoxacin was assessed in preclinical studies. MATERIALS & METHODS: Ozenoxacin or ofloxacin (300 mg/kg/day for 5 days, for each compound) was orally administered to juvenile rats, and oral ozenoxacin (10-100 mg/kg/day for 14 days) was administered to juvenile dogs. RESULTS: In juvenile rats, ozenoxacin showed no chondrotoxicity, whereas ofloxacin produced typical quinolone-induced lesions in articular cartilage in three of ten rats. Oral ozenoxacin administration to juvenile dogs showed no chondrotoxicity or toxicologically relevant findings in selected target organs. CONCLUSION: Ozenoxacin was generally well-tolerated in juvenile rats and dogs, with no evidence of quinolone-induced arthropathy.

Pregnancy outcomes in women reporting exposure to ofloxacin in early pregnancy.

This study aimed to analyse perinatal outcomes in ofloxacin-exposed pregnancies. This prospective study was conducted on 143 singleton pregnancies between January 2001 and April 2014, after oral ofloxacin exposure in the first trimester. A total of 33 exposed mothers were compared with 110 age-matched controls who were not exposed to teratogen. The mean maternal age was 31.4 ± 3.6 years, and the median gestational age was 4.1 weeks at the exposure. No significant differences were observed in either gestational age or in the foetal ultrasonographic long bone length between the exposed and control groups. Spontaneous abortions occurred without a significant difference (6.1% versus 10.0%, p = .733). In addition, no significant differences were found in either the stillbirths or in the major birth defects between the exposed and control groups (0% versus 2.0%, p = 1.000 and 0% versus 4.0%, p = .572, respectively). Ofloxacin has no significant effect on perinatal outcomes. Impact statement What is already known on this subject? Ofloxacin and other quinolones are avoided during pregnancy because of concerns about cartilage toxicity. But we do not find human data reporting such toxicity in a case report. What the results of this study add? Previous studies were designed for evaluation of just congenital anomaly. But in this study, we measured the fetal long bone length to replace for evaluation of fetal cartilage toxicity. In fetal stage, we can not measure the cartilage of fetus. so we measure fetal long bone length for evaluation that ofloxacin might influence to fetal cartilage growth. Even though this sample size is small. this results will be helpful to counsel pregnant women who exposed to ofloxacin during pregnancy.