Histopathological lesions, P-glycoprotein and PCNA expression in zebrafish (Danio rerio) liver after a single exposure to diethylnitrosamine

Machado, Sandrine P.; Cunha, Virgínia; Reis-Henriques, M.A.; Ferreira, Marta

doi:10.1016/j.etap.2014.09.002

Cited by 16 publications

(7 citation statements)

References 73 publications

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“…Further to K factor, HSI is also a simple initial screening index largely used (Van der Oost et al, 2003). Fish exposed to contaminants usually present a higher HSI in comparison to those from pristine areas, because there is an increased detoxification activity of the liver in response to the presence of the toxic compounds (Dragun et al, 2013;Machado et al, 2014;Pereira et al, 1993;Van Dyk et al, 2012). Higher HSI could also be related to reproduction, but all the fish used in this work were not mature.…”

Section: Discussionmentioning

confidence: 99%

Citogenotoxic response of juvenile cobia Rachycentron canadum (Linnaeus, 1766) reared in two different systems

et al. 2018

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Aquaculture production is continuously growing worldwide, and marine fish farming in Brazil is still in its infancy. Intensive farming conditions may cause physiological stress to the cultured organism, which can be evaluated by citogenotoxic biomarkers. The aim of this study was to assess the genotoxic effect of the rearing conditions in red blood cells of juvenile cobia Rachycentron canadum by using comet assay and micronucleus and other nuclear abnormalities assay. Juvenile cobia were reared for 13 weeks in indoor tank with open water circulation and in near shore cage. The comet assay and the nuclear abnormalities assay detected higher DNA damage and higher nuclear abnormalities frequency in erythrocytes of fish reared in the indoor tank. Results showed that two methods are complementary. Additionally, cobia were injected with ß-naphthoflavone (BNF) at concentrations of 2mgkg-1 and 10mgkg-1 in laboratory controlled conditions, and maintained for 7 days in separate tanks to better understand the response mechanisms of this species to a toxic substance. The comet assay did not detect any significant differences between BNF injected and control fish, whereas nuclear abnormalities assay showed significant differences between BNF injected and the control groups. The damages identified by the comet assay are repairable breaks in the DNA strands, whereas nuclear abnormalities may be permanent. Possibly the period of maintenance after injection was enough to clean BNF from the organisms and to repair the breaks in the DNA strands. As cobia seems to respond very well to genotoxic elements, comet assay and nuclear abnormalities assay would be useful tools to monitor farming conditions.

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Section: Discussionmentioning

confidence: 99%

Citogenotoxic response of juvenile cobia Rachycentron canadum (Linnaeus, 1766) reared in two different systems

et al. 2018

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“…In general, up-regulation of hepatic P-gp was reported to be linked to the toxic effects of several compounds, including diethylnitrosamine, zinc pyrithione and uremic toxin indoxyl sulfate [41][42][43]. The effect of the latter compound was tested on 14 different transporter genes, and only the gene encoding P-gp; ABCB1, was up-regulated, indicating its crucial role in hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats

El-Sheikh

2020

Sci. Pharm.

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To investigate combined effect of the anticancer drug cisplatin (CP) and the opiate analgesic morphine (MOR) on liver, rats were administered MOR (10 mg/kg/day i.p. for 10 days), with or without CP (7.5 mg/kg i.p. once at day 5 of the study). MOR or CP alone caused deterioration of liver function tests and induced damage to histological architecture of liver. In addition, each drug alone caused hepatic oxidative stress, as evident by significant increase of malondialdehyde and nitric oxide, as well as the significant decrease in GSH, catalase and SOD compared to control. Administration of either MOR or CP also caused liver inflammation, evident by the increase in the pro-inflammatory cytokines; TNF-α and IL-6. In addition, either MOR or CP induced liver apoptosis, as shown by significant increase in expression of the pro-apoptotic marker; caspase 3 compared to control. Either MOR or CP also caused up-regulation of the efflux transporter P-glycoprotein (P-gp). Combining MOR with CP caused deterioration in all parameters tested compared to CP alone. Thus, treatment with MOR worsened CP-induced hepatotoxicity through oxidative stress, inflammation and apoptosis mechanisms. In addition, both drugs contributed to the up-regulation of P-gp, which might be a new mechanism for their hepatotoxic effects.

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“…Glycosides are converted to aglycons in the zebrafish gut, followed by sulfation, glucuronidation, methylation, and other conjugations, similar to those in mammals (Hung et al, 2012). Several molecules involved in drug metabolism, such as CYPs and P-glycoprotein, are also conserved in zebrafish (Bresolin et al, 2005;Machado et al, 2014). However, studies on the kinetics of drugs after absorption and studies to identify enzymes involved in drug metabolism have rarely been conducted in zebrafish.…”

Section: Evaluation Of Effective Herbal Medicines In Ninjinyoeito For...mentioning

confidence: 99%

Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish

et al. 2022

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Sociability is an essential component of the linkage structure in human and other vertebrate communication. Low sociability is defined as a poor social approach, including social withdrawal and apathy, and is implicated in a variety of psychiatric disorders. Ninjinyoeito (NYT), a traditional Japanese herbal medicine, has been used in the medical field. This study aimed to determine the effect of NYT on low sociality in NPY-KO zebrafish. NPY-KO zebrafish were fed a 3% NYT-supplemented diet for 4 days and subjected to behavioral tests. In the mirror test, NPY-KO zebrafish fed a control diet showed avoidance behavior toward their mirror counterparts. In contrast, the treatment of NPY-KO zebrafish with NYT significantly increased their interaction with their counterparts in the mirror. In addition, a 3-chambers test was conducted to confirm the effect of NYT on the low sociality of NPY-KO zebrafish. NPY-KO zebrafish fed the control diet showed less interaction with fish chambers, while NYT treatment increased the interaction. Phosphorylation of ERK, a marker of neuronal activity, was significantly reduced in the whole brain of NYT-fed NPY-KO zebrafish, compared to the control diet. NYT treatment significantly suppressed hypothalamic-pituitary-adrenal-related genes (gr, pomc, and crh) and sympathetic-adrenal-medullary-related genes (th1, th2, and cck) in NPY-KO zebrafish. NYT administration significantly reduced mRNA levels of gad1b compared to the control diet, suggesting the involvement of GABAergic neurons in NYT-induced improvement of low sociability. Furthermore, the expression of CREB was suppressed when NPY-KO zebrafish were fed NYT. Next, we attempted to identify the effective herb responsible for the NYT-induced improvement of low sociability. NPY-KO zebrafish were fed an experimental diet containing the target herb for 4 days, and its effect on sociability was evaluated using the 3-chambers test. Results showed that Cinnamon Bark and Polygala Root treatments significantly increased time spent in the fish tank area compared to the control diet, while the other 10 herbs did not. We confirmed that these two herbs suppressed the activity of HPA-, SAM-, and GABAergic neurons, as well as NYT-treated zebrafish, accompanied by downregulation of CREB signaling. This study suggests the potential use of NYT as a drug for sociability disorders.

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Histopathological lesions, P-glycoprotein and PCNA expression in zebrafish (Danio rerio) liver after a single exposure to diethylnitrosamine

Cited by 16 publications

References 73 publications

Citogenotoxic response of juvenile cobia Rachycentron canadum (Linnaeus, 1766) reared in two different systems

Citogenotoxic response of juvenile cobia Rachycentron canadum (Linnaeus, 1766) reared in two different systems

P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats

Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish

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