Low concentrations of ciprofloxacin alone and in combination with paracetamol induce oxidative stress, upregulation of apoptotic-related genes, histological alterations in the liver, and genotoxicity in Danio rerio

Nowadays, there are countless articles about the harmful effects of paracetamol (PCM) in non-target organisms. Nonetheless, information regarding the toxicity of ciprofloxacin (CPX) and the CPX-PCM mixture is still limited. Herein, we aimed to evaluate the hepatotoxic and genotoxic effects that cipr...

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Published in:Chemosphere (Oxford) 2022-05, Vol.294, p.133667-133667, Article 133667
Main Authors: Elizalde-Velázquez, Gustavo Axel, Rosas-Ramírez, Jonathan Ricardo, Raldua, Demetrio, García-Medina, Sandra, Orozco-Hernández, José Manuel, Rosales- Pérez, Karina, Islas-Flores, Hariz, Galar-Martínez, Marcela, Guzmán-García, Xochitl, Gómez-Oliván, Leobardo Manuel
Format: Article
Language:English
Subjects:
Acetaminophen - toxicity
Animals
Apoptosis
Biochemical changes
Ciprofloxacin
Ciprofloxacin - toxicity
DNA Damage
Histopathological alterations
Liver
Oxidative damage
Oxidative Stress
Up-Regulation
Water Pollutants, Chemical - toxicity
Zebrafish - genetics
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Summary:Nowadays, there are countless articles about the harmful effects of paracetamol (PCM) in non-target organisms. Nonetheless, information regarding the toxicity of ciprofloxacin (CPX) and the CPX-PCM mixture is still limited. Herein, we aimed to evaluate the hepatotoxic and genotoxic effects that ciprofloxacin alone and in combination with paracetamol may induce in Danio rerio adults. For this purpose, we exposed several D. rerio adults to three environmentally relevant concentrations of PCM (0.125, 0.250, and 0.500 μg/L), CPX (0.250, 0.500, and 1 μg/L), and their mixture (0.125 + 0.250, 0.250 + 0.500, and 0.500 + 1 μg/L) for 96 h. The blood samples showed CPX alone and in combination with PCM damaged the liver function of fish by increasing the serum levels of liver enzymes alanine aminotransferase and alkaline phosphatase. Moreover, our histopathological study demonstrated liver of fish suffered several tissue alterations, such as congestion, hyperemia, infiltration, sinusoidal dilatation, macrovascular fatty degeneration, and pyknotic nuclei after exposure to CPX alone and in combination with PCM. Concerning oxidative stress biomarkers and the expression of genes, we demonstrated that CPX and its mixture, with PCM, increased the levels of antioxidant enzymes and oxidative damage biomarkers and altered the expression of Nrf1, Nrf2, BAX, and CASP3, 6, 8, and 9 in the liver of fish. Last but not least, we demonstrated CPX alone and with PCM induced DNA damage via comet assay and increased the frequency of micronuclei in a concentration-dependent manner in fish. Overall, our results let us point out CPX, even at low concentrations, induces hepatotoxic effects in fish and that its combination with PCM has a negative synergic effect in the liver of this organism. [Display omitted] •The liver function of fish was affected after 96 h of exposure to ciprofloxacin.•Apoptosis- and oxidative stress gene-related were upregulated by ciprofloxacin.•Ciprofloxacin induced a significant oxidative stress response in the liver fish.•By the comet assay and micronuclei test, we found that ciprofloxacin induced genotoxicity.•Mixtures produced more damage in all biomarkers compared to ciprofloxacin alone.
ISSN:0045-6535
1879-1298
DOI:10.1016/j.chemosphere.2022.133667