chlortetracycline and Atherosclerosis

β-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.

Topics: Animals; Anti-Bacterial Agents; Atherosclerosis; Chlortetracycline; Cholesterol; Ciprofloxacin; Computational Biology; Disease Models, Animal; Doxycycline; Enrofloxacin; Female; Hyperlipidemias; Larva; Lipid Metabolism; Male; MicroRNAs; Ofloxacin; Oxytetracycline; Peroxisome Proliferator-Activated Receptors; Triglycerides; Up-Regulation; Zebrafish; Zebrafish Proteins

The objective of this study is to characterize arterial tissue with and without atherosclerosis by fluorescence lifetime imaging microscopy (FLIM) using Europium Chlortetracycline complex (EuCTc) as fluorescent marker. For this study, twelve rabbits were randomly divided into a control group (CG) and an experimental group (EG), where they were fed a normal and hypercholesterolemic diet, respectively, and were treated for 60 days. Cryosections of the aortic arch specimens were cut in a vertical plane, mounted on glass slides, and stained with Europium (Eu), Chlortetracycline (CTc), Europium Chlortetracycline (EuCTc), and Europium Chlortetracycline Magnesium (EuCTcMg) solutions. FLIM images were obtained with excitation at 405 nm. The average autofluorescence lifetime within plaque depositions was ~1.36 ns. Reduced plaque autofluorescence lifetimes of 0.23 and 0.31 ns were observed on incubation with EuCTc and EuCTcMg respectively. It was observed a quenching of collagen, cholesterol and TG emission spectra increasing EuCTc concentration. The drastic reduction in fluorescence lifetimes is due to a resonant energy transfer between collagen, triglycerides, cholesterol and europium complexes, quenching fluorescence.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Atherosclerosis; Chlortetracycline; Cholesterol, Dietary; Collagen; Disease Models, Animal; Energy Transfer; Europium; Fluorescent Dyes; Microscopy, Fluorescence; Plaque, Atherosclerotic; Rabbits; Time Factors; Triglycerides

Topics: Animals; Arteriosclerosis; Atherosclerosis; Chlortetracycline; Rabbits