Joint toxicity of fluoroquinolone and tetracycline antibiotics to zebrafish (<i>Danio rerio</i>) based on biochemical biomarkers and histopathological observation

Abstract

-Herein, we report on the joint toxicity of four fluoroquinolones and two tetracyclines (β-diketone antibiotics-DKAs) to zebrafish based on a series of toxicological endpoints and histopathological observations. A positive dose-dependence was observed in DKA-exposure groups with a 72-hpf EC 50 of 130.3 mg/L for hatching rate, 120-hpf LC 50 of 149.8 mg/L, and 120-hpf EC 50 of 135.1 mg/L for malformation rate. When zebrafish at 60 dpf were exposed to a series of DKA concentrations (45, 60 and 90 mg/L) for 7, 14 and 21 days, creatine kinase and AChE activities were significantly induced, and intracellular malondialdehyde increased in all treatments except for the 45 mg/L treatment. The transcription levels of AHRRa from livers were significantly (p < 0.05) up-regulated in all treatments after two months of DKA exposure. CKma expression from skeletal muscle was significantly down-regulated in the 90 mg/L treatment. A remarkable down-regulation of CYP3A65 was observed in the 60 mg/L treatment. DKA exposure resulted in severe tissue damage including mitochondria swelling, reduction of mitochondrial cristae, deepening of mitochondrial cristae bands, and decreasing and even disappearance of the rough endoplasmic reticulum. Total sperm motility was decreased by ca. 30% due to DKA exposure. These results provide important information for toxicity and health risks due to mixed DKA exposure in aquatic environments.

Zebrafish as a Screening Model to Study the Single and Joint Effects of Antibiotics

“…They demonstrated that TCs played a key role in the mixtures, and their simultaneous presence mainly had antagonistic actions. A similar result has been reported by Ding et al [ 38 ], with the TCs having a stronger effect than the DKAs, as the 120 hpf LC50 value for the malformation rate due to the exposure to the antibiotic mixtures was 149.8 mg/L, and for TCs, it was 18.3 mg/L. In contrast with previous results, the joint antibiotic toxicity of sulfamonomethoxine, cefotaxime sodium, tetracycline and enrofloxacin was more severe than that of a single treatment [ 83 ].…”

“…In accordance with the results of the previous study, Qiu et al [ 83 ] indicated that treatment with sulfonamide β-lactamtetracycline and quinolone antibiotics could affect the ROS content in zebrafish larvae. Changes in creatine kinase activity and creatinine concentration, which are related to muscle contraction and energy transfer, were observed in zebrafish after exposure to a series of DKA concentrations [ 38 ].…”

“…Most of the research papers on this topic have reported that the zebrafish health or/and its capacity to respond to environmental changes are affected following both acute and chronic exposure to antibiotics. The toxicological effects of single and mixed antibiotics in zebrafish were studied by proteomic [ 30 ] and transcriptome sequencing [ 31 , 32 ], examination of behavioral activities [ 28 , 33 , 34 ] and biomarkers [ 35 , 36 ], histopathological analysis of various tissues [ 30 , 37 ], fish lethality assays (LC 50 ) [ 22 , 38 , 39 ] and following the fish morphological changes [ 40 ]. Antibiotics were found to interfere with the bacterial communities of zebrafish gut and with fish development, causing malformations, such as hatching delay, shorter body length, yolk sac edema, curved body axis and pericardial edema [ 23 , 25 , 41 , 42 , 43 , 44 ].…”

Drug-Induced Mitochondrial Toxicity in the Geriatric Population: Challenges and Future Directions

“…It has been reported that elderly patients taking cholesterol lowering drugs (Zocor, Lipitor, etc.) have shown drug–drug interactions (DDI), particularly with the anti-lipidemic drug Lopid (gemfibrozil [53,106]), but also with certain antibiotic classes, such as macrolides [107,108] and fluoroquinolones [109,110] and the heart medication, Nexteron (amiodarone) [64,111]. All of these drugs have been shown to cause mitochondrial toxicity by targeting a variety of, as well as multiple, mitochondrial mechanisms/targets.…”

Potential adverse effects of ciprofloxacin and tetracycline on ARPE-19 cell lines

“…However, in a Zebrafish model ( Danio rario ), Ding et al found that TETRA induced damage at several concentrations (45, 60 and 90 mg/L) after 7, 14 and 21 days with mitochondrial damage, including diminished mitochondrial cristae and mitochondrial swelling. 32 Another study in hepatocytes showed significant negative influences on mitochondrial calcium uniporter with treatment after TETRA derived compounds (50 uM, 22.22 g). TETRA prevented Ca 2+ uptake by mitochondria and then inhibited the inducement of mitochondrial permeability transmission by Ca 2+ .…”