Genotoxic and cytotoxic alterations induced by environmentally-relevant concentrations of amoxicillin in blood cells of Cyprinus carpio

Orozco-Hernández, José Manuel; Gómez-Oliván, Leobardo Manuel; Heredia-García, Gerardo; Luja-Mondragón, Marlenee; Islas-Flores, Hariz; SanJuan-Reyes, Nely; Galár-Martínez, Marcela; García-Medina, Sandra; Dublán‐García, Octavio

doi:10.1016/j.chemosphere.2019.07.054

Cited by 13 publications

(7 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some human and veterinary antibiotics are capable of inducing hormesis in plants (Agathokleous et al, 2018). Also the results obtained in our study could be related to the ability of AMX at concentrations of 0.039 and 1.67 μgL −1 to induce genotoxic and cytotoxic effects in species such as Cyprinus carpio, since these effects are often related to embryotoxic and teratogenic effects (Orozco-Hernández et al, 2019).…”

Section: Discussionsupporting

confidence: 56%

“…Previous studies in our research group demonstrate that the AMX generate oxidative stress, genotoxicity, and cytotoxicity in Cyprinus carpio (Elizalde-Velázquez et al, 2017;Orozco-Hernández et al, 2019). Our hypothesis that the AMX is capable to induce alterations to embryonic development and teratogenicity in D. rerio is supported by oxidative stress involved in the etiology of defective embryo development (Guérin et al, 2001).…”

Section: Introductionmentioning

confidence: 54%

“…Two recent studies carried out by our group demonstrated that (1) AMX at concentrations of 10 ngL −1 and 10 μgL −1 generated an increase in the levels of lipoperoxidation, hydroperoxide content, and carbonylated protein content, as well as superoxide dismutase, catalase, and glutathione peroxidase in the brain, kidney, and gills of Cyprinus carpio (Elizalde-Velázquez et al, 2017) and (2) AMX in environmentally relevant concentrations, 0.039 μgL −1 and 1.67 μgL −1 , was capable of generating genotoxic alterations and cytotoxic effects in blood cells of the common carp (Orozco-Hernández et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Developmental Effects of Amoxicillin at Environmentally Relevant Concentration Using Zebrafish Embryotoxicity Test (ZET)

González-González

Gómez-Oliván

Islas-Flores

et al. 2021

Water Air Soil Pollut

Self Cite

View full text Add to dashboard Cite

Amoxicillin (AMX) is an antibiotic that has been added to the watch list of substances by the European Union, through the Water Framework Directive (WFD; 2000/60/EC) and its daughter regulation (Decision 2018/840) for which monitoring data have to be gathered with a possibility for future regulation. Previous studies have demonstrated that this antibiotic generates toxic effects, among which oxidative stress in aquatic organisms is noteworthy. The aim of this study was to evaluate the effect on embryonic development and the teratogenic effects induced by AMX at environmentally relevant concentrations in oocytes and embryos of Danio rerio. Furthermore, oxidative stress biomarkers were evaluated at 72 and 96 hpf. The LC 50 was 14.192 μgL −1 , EC 50 was 7.083 μgL −1 , and TI was 2.003. Biomarkers of cellular oxidation and antioxidant enzymes were modified in a concentration-dependent way with respect to the control group (p<0.05). The main malformations identified were tail malformation, pericardial edema, yolk sac malformation, scoliosis, pectoral fin absence, and no hatching. The results allow us to conclude that AMX at environmentally relevant concentrations is capable of inducing embryotoxic and teratogenic effects and oxidative damage. This compound represents a risk to aquatic organisms such as Danio rerio. Clinical Trials Registration Not applicable.

show abstract

Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Developmental Effects of Amoxicillin at Environmentally Relevant Concentration Using Zebrafish Embryotoxicity Test (ZET)

González-González

Gómez-Oliván

Islas-Flores

et al. 2021

Water Air Soil Pollut

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the blood cells of Cyprinus carpio, AMX induced DNA damage and cytotoxic effects with a significant increase of micronucleus frequency and DNA fragmentation at environmentally realistic concentrations of 0.039 µg/L and 1.67 µg/L (Orozco-Hernández et al, 2019). Furthermore, in an in vitro study, Lacaze et al (2015) observed that TMP was genotoxic at 200 µg/L and immunotoxic at 20 mg/L on haemocytes of Mytilus edulis.…”

Section: Discussionmentioning

confidence: 97%

Effects of Three Widely Used Antibiotics and Their Mixture on the Haemocytes of the Clam Ruditapes philippinarum

Nicolussi

Fabrello

Asnicar

et al. 2022

Front. Environ. Sci.

View full text Add to dashboard Cite

Although the presence of pharmaceutical and personal care products in aquatic ecosystems is well documented, little information is available about their sublethal effects, on aquatic invertebrates. From an ecotoxicological point of view, the use of in vitro approaches has been recommended as a tool to assess adverse effects and to understand the mechanisms of action of chemicals at the cellular level. In the present in vitro study, the effects of Amoxicillin (AMX), Trimethoprim (TMP) and Ciprofloxacin (CIP) (1 µg/L, each) were tested alone and—for the first time—as a mixture (MIX) on haemocytes of the clam Ruditapes philippinarum. After the exposure, a battery of cellular parameters was evaluated, such as haemocyte viability, lysosomal membrane stability, superoxide anion production, acid phosphatase activity, the frequency of micronuclei and chromosomal aberrations. The results demonstrated that AMX, TMP, CIP and MIX affected lysosomal membrane stability, as well as superoxide anion and acid phosphatase production, and promoted chromosomal aberrations. This study highlighted that Manila clam haemocytes are a sensitive cell model to assess the effects of exposure to pharmaceutical products on non-target species. Our study demonstrated that the effects of pharmaceutical mixtures on marine species should be experimentally evaluated because they are not predictable from single exposures as the compounds can interact in different ways on the various biological endpoints considered.

show abstract

“…Conventional drugs administered in new ways or prepared as compound formulations might be a strategy to combat antibiotic resistance and increase antibiotic sensitivity [ 6 ]. Amoxicillin (AMO), a classic antibiotic, has been in use since the 1970s [ 7 ]; this antibiotic is a pharmaceutical widely employed in veterinary medicine worldwide [ 8 ], such as for the control of severe, systemic infections such as Streptococcus in pigs [ 9 ]. However, with the advent of the antibiotic era, the overuse and inappropriate consumption and application of antibiotics have driven the rapid emergence of multidrug-resistant pathogens [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Development of an amoxicillin-radix scutellaria extract formulation and evaluation of its pharmacokinetics in pigs

Yi,

Wen,

et al. 2023

BMC Vet Res

View full text Add to dashboard Cite

Background A new antibacterial compound powder of amoxicillin (AMO)/Radix Scutellaria extract (RSE) was developed, and its pharmacokinetics were determined in pigs following oral administration. Results The MIC ranges of AMO against Escherichia coli, Staphylococcus aureus and Streptococcus were 1–8 μg/mL, 0.5–4 μg/mL and 0.5–64 μg/mL, respectively. The MIC ranges of RSE against E. coli, S. aureus, and Streptococcus were greater than 2.5 mg/mL, 0.156–2.5 mg/mL, and greater than 2.5 mg/mL, respectively. For S. aureus, the combined drug susceptibility test showed that AMO and RSE had an additive or synergistic effect. The results of compatibility test, the excipient screening test and the drug quality control test showed that the formulation had stable quality and uniform properties under the test conditions. Two studies were conducted to investigate the pharmacokinetics of the compound product in pigs. First, the pharmacokinetics of the AMO-RSE powder were compared with those of their respective single products. The results showed no significant change in the main pharmacokinetic parameters when either component was removed from the compound formulation; thus, AMO and RSE have no pharmacokinetic interaction in pigs. Second, pigs were orally administered three different doses of AMO-RSE powder. The Cmax and AUC increased proportionally with increasing p.o. dose; thus, the λz, t1/2λ, MRT, and Tmax were unchanged for the doses of 10, 20, and 30 mg/kg AMO and the doses of 5, 10, and 15 mg/kg BCL, showing that AMO/baicalin in AMO-RSE powder showed linear pharmacokinetic characteristics in pigs. Conclusions The combined drug sensitivity test of AMO and RSE against S. aureus showed that the combination was additive or synergistic. Pharmacokinetic studies indicated that AMO and BCL do not interfere with each other in pigs when used in a compound formulation. The pharmacokinetic parameters remained unchanged regardless of the dose for p.o. administration, indicating linear pharmacokinetic properties over the tested dose range. The quality of the AMO-RSE powder was good and stable, providing a foundation for its clinical application in veterinary medicine. Further bioavailability, PK/PD and clinical trials are still needed to determine the final dosage regimen.

show abstract

Genotoxic and cytotoxic alterations induced by environmentally-relevant concentrations of amoxicillin in blood cells of Cyprinus carpio

Cited by 13 publications

References 53 publications

Developmental Effects of Amoxicillin at Environmentally Relevant Concentration Using Zebrafish Embryotoxicity Test (ZET)

Developmental Effects of Amoxicillin at Environmentally Relevant Concentration Using Zebrafish Embryotoxicity Test (ZET)

Effects of Three Widely Used Antibiotics and Their Mixture on the Haemocytes of the Clam Ruditapes philippinarum

Development of an amoxicillin-radix scutellaria extract formulation and evaluation of its pharmacokinetics in pigs

Contact Info

Product

Resources

About