Abstract
The objective of this study was to investigate the effects of difloxacin (DIF) and avermectin (AVM) on glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T) in different tissues of crucian carp (Carassius auratus gibelio). After the treatments of DIF and AVM, the mRNA expressions of GAD and GABA-T in different tissues were detected by quantitative real-time PCR (qPCR). The results showed that the mRNA expressions of GAD65, GAD67, and GABA-T in the telencephalon (Tel), mesencephalon (Mes), cerebella (Cer), and medulla oblongata (Med) were downregulated significantly with the safe dose (SD, 20 mg/kg) of DIF (P < 0.05 or P < 0.01). While the expressions of GAD65 and GAD67 in the kidney at 12 h had strikingly upregulated to 13.81 ± 1.06** and 150.67 ± 12.85** times. Treated with the lethal dose of 50% (LD50, 2840 mg/kg b. W.) of DIF, the mRNA expressions of GAD65, GAD67, and GABA-T in all tissues were increased significantly (P < 0.01). The results of AVM group showed that the mRNA expressions of GAD65, GAD67, and GABA-T both in the central and peripheral tissues were all remarkably downregulated at the safe concentration (SC, 0.0039 mg/L) and the lethal concentration of 50% (LC50, 0.039 mg/L), except for the mRNA inhibitions of GAD65, GAD67, and GABA-T in the muscle at 2 h which sharply downregulated to 0.20 ± 0.02ΔΔ × 10−2, 0.57 ± 0.06ΔΔ × 10−1 and 0.44 ± 0.02ΔΔ × 10−1, respectively (P < 0.01).
Similar content being viewed by others
Introduction
GABA, an important inhibitory neurotransmitter in many organisms, along with glutamate (Glu), is involved in the neuromodulation of most synaptic activity. GABA arises via decarboxylation of L-glutamate by glutamate decarboxylase (GAD) (Chung et al. 1992) and is metabolized subsequently via GABA-transferase (GABA-T) to succinic semialdehyde, which is then oxidized to succinate (Wood et al. 1978). This process would directly affect the accumulations of GABA in organisms. The changes of Glu and GABA in nerve endings would result in rearrangements of the nervous system that increases neural activity (Nasreen et al. 2012). The production and metabolism of GABA can be predicted by observing changes in the expression of enzymes present in nerve endings.
However, many factors affect how well GABA works, which include heavy metal (Struzyńska and Sulkowski 2004), antibiotics (Matsuo et al. 1998), insecticide (Sánchez-Borzone et al. 2017), and other biological toxins (Kudryavtsev et al. 2015). The imbalances of excitatory or inhibitory neurotransmitters caused by drugs can lead to nerve abnormalities, causing organisms to exhibit symptoms of nerve poisoning.
Fluoroquinolones (FQs) were widely used in aquaculture due to its good bactericidal effect in China. Its family includes difloxacin (DIF), ofloxacin, pefloxacin, enoxacin, norfloxacin, etc. However, the side effects of FQs have been widely reported in recent years, such as its muscular toxicity (Demetrious 2018), renal toxicity (Owens and Ambrose 2005), and neurotoxicity (Xiao et al. 2018). Many reports suggested FQs could have caused severe neurotoxic reactions, which lead to hallucinations, depression, and other neurological diseases (Barrett and Login 2009; Grill and Maganti 2011; Guiol et al. 1993). It had been reported that norfloxacin (Xi et al. 2019) and DIF (Ruan et al. 2014a) caused non-target biological neurotoxicity. Albino male mice treated with ciprofloxacin were found the levels of Glu and GABA significantly reduced (Arafa et al. 2015). While as a broad-spectrum insecticide, avermectin (AVM) was also widely used for parasites killing in aquaculture. The problems of non-target biological poisoning caused by AVM were becoming more and more serious, including in birds (de Faria et al. 2018a, b), fish (Novelli et al. 2016), batrachians (Vasconcelos et al. 2016), and mammals (Nasr et al. 2016). Experiments on Danio rerio (Weichert et al. 2017), mice (Da et al. 2018), and pigeon (Li et al. 2013) had been found that AVM could cause neurotoxicity. On specific physiological and biochemical indicators, AVM exposure enhanced the contents of GABA, glycine, Glu, and aspartic acid in the cerebrum, cerebellum, and optic lobe of American king pigeons significantly (Chen et al. 2014). Crucian carp (Carassius auratus gibelio) is one of the tremendous economic value fish which widely cultivated in China. Therefore, this paper intends to study the possible variations of GABA’s synthetase and metabolic enzyme in crucian carp after treated with DIF and AVM.
Materials and methods
Experimental animals and fishery drugs
Crucian carp were bought from a farm in Nantong City, Jiangsu Province, east of China as experimental fish, which body weights were 50.04 ± 3.12 g, and fed for 2 weeks before the beginning of the experiments. Plenty of oxygen was pumped into the water during the whole experiment. Temperature and pH values were maintained in the right range of crucian carp. All the fish were fed twice per day.
The SD and the lethal dose of 50% at 96 h (96 h LD50) of DIF were 20 mg/kg b. W. and 2840 mg/kg b. W. which referred from the previous study (Ruan et al. 2014a). According to the body weights of the experimental fish, DIF was singly orally administered into the foregut of the experimental fish.
The SC and 96 h LC50 of AVM were 0.0039 mg/L and 0.039 mg/L by the method of single bath administration (Ruan et al. 2013).
The sample collections
The experimental fish were randomly divided into three groups at the corresponding dose/concentration, 60 fish per group. Samples of Tel, Mes, Cer, Med, liver, kidney, and muscle were collected and stored at − 80 °C for the mRNA extractions. All fish were handled following the “Regulation on Animal Experimentation.”
Total RNA extraction, reverse transcription, RT-PCR analysis, and qPCR analysis
The procedures of total RNA extraction, RT-PCR, and qPCR analysis were referred from the previous article (Ruan et al. 2014b). The primers pairs were shown in the Table 1.
Data processing
The comparative threshold method (2-ΔΔCT) was employed to calculate the relative expression of the genes. The data were expressed as mean ± standard deviation (SD) and SPSS 17.0 (Chicago, IL, USA) was used for one-way ANOVA, where P < 0.05 and P < 0.01, respectively, indicated significant and extremely significant difference.
Results and analysis
Analysis of genes expressions in the brain at the SD of DIF
From Fig. 1 a and b, it could be found that GAD65 and GAD67 expressions were significantly suppressed (P < 0.01) in the crucian carp’s brain by SD of DIF (20 mg/kg b. W.) after treatment at 0.083, 2, and 120 h. The volumes and the time-points which GAD65 expressions remarkably inhibited were 0.25 ± 0.05ΔΔ at 0.083 h in Tel, 0.12 ± 0.01ΔΔ at 12 h in Med, and 0.18 ± 0.01ΔΔ at 120 h in Mes, respectively (Fig. 1a). GAD67 levels were strongly suppressed in Med, and the changes in which were 0.46 ± 0.06ΔΔ times at 0.083 h, 0.22 ± 0.01ΔΔ times at 12 h, and 0.30 ± 0.01ΔΔ times at 120 h times (Fig. 1b). The same as GAD67, GABA-T gene in Med and the changes of which were 0.57 ± 0.02ΔΔ times at 0.083 h, 0.37 ± 0.03ΔΔ times at 12 h, and 0.55 ± 0.06ΔΔ times at 120 h (Fig. 1c). However, GABA-T levels were significantly upregulated in Tel and Cer at 120 h, and their volumes were 1.21 ± 0.20** and 1.55 ± 0.14** (P < 0.01).
Note: 0.083 h, 12 h, and 120 h were the three-time points of DIF at the SD (20 mg/kg b. W.) (Ruan et al. 2014a). “Δ” and “ΔΔ” mean significant (P < 0.05) or extremely significant (P < 0.01) downregulation, while “*” and “**” mean significant (P < 0.05) or extremely significant (P < 0.01) upregulation. The same as followed.
Analysis of mRNA expressions in peripheral tissues at the SD of DIF
GAD expressions in the peripheral tissues were extremely significant inhibited by DIF (P < 0.01). As shown in Fig. 2 a and b and, GAD65 and GAD67 genes were suppressed to minimums for 0.12 ± 0.01ΔΔ and 0.22 ± 0.01ΔΔ at 12 h, while GABA-T genes were significantly upregulated in the liver. The maximum changes of GABA-T were 1.76 ± 0.18** times at 120 h in the liver (Fig. 2c). GAD and GABA-T levels appeared consistent trends as first decreasing, then increasing, and decreasing in the kidney. Among them, GAD65 levels were 0.19 ± 0.05ΔΔ at 0.083 h, 13.81 ± 1.06** at 12 h, and 0.36 ± 0.05ΔΔ at 120 h (Fig. 3a), while GAD67 levels were 0.37 ± 0.08ΔΔ at 0.083 h, 150.67 ± 12.85** at 12 h, and 3.64 ± 0.28* at 120 h (Fig. 3b). Moreover, GABA-T gene were 1.02 ± 0.02* at 0.083 h, 5.22 ± 0.22** at 12 h, and 0.25 ± 0.01ΔΔ at 120 h (Fig. 3c). GAD65 level was greatly inhibited in the muscle, and its minimum value was 0.04 ± 0.008ΔΔ at 0.083 h (Fig. 4a), while GAD67 level was extremely significant increased with a maximum change of 2.89 ± 0.58** times at 12 h (Fig. 4b). GABA-T levels were 0.68 ± 0.05ΔΔ at 0.083 h, 1.37 ± 0.14** at 12 h, and 0.93 ± 0.08ΔΔ at 120 h (Fig. 4c), which also showed a same trend as “decreasing—increasing—decreasing.”
Analysis of mRNA expressions at LD50 of DIF
The GAD65, GAD67, and GABA-T levels were extremely increased both in the brain and peripheral tissues of the crucian carp at LD50 of DIF (P < 0.01, Tables 2 and 3). The volumes of extremely stimulated GAD65, GAD67, and GABA-T levels were 2.25 ± 0.16** in Cer, 2.41 ± 0.09** in Tel, and 1.97 ± 0.23** in Med (Table 2). As in the kidney, GAD65 and GAD67 levels were significantly increased by 3.81 ± 0.19** and 8.46 ± 1.43**. A phenomenon in the muscle was that GAD65 level was suppressed by 0.32 ± 0.03ΔΔ times at 0.083 h, while GAD67 and GABA-T levels were raised to 14.19 ± 1.25** times and 1.12 ± 0.18** times (Table 2).
Analysis of mRNA expressions in the brain at the SC of AVM
Treated by AVM, the levels of GAD65, GAD67, and GABA-T were extremely inhibited in the brain (P < 0.01, Fig. 5). The volumes and the time-points which GAD65 expressions remarkably inhibited were 0.16 ± 0.01ΔΔ at 0.083 h in Mer, 0.17 ± 0.01ΔΔ at 2 h in Med, and 0.20 ± 0.02ΔΔ at 120 h in Mes, respectively (Fig. 5a). There were significantly downregulated GAD67 gene expressions in Med, which of the gene levels were 0.19 ± 0.02ΔΔ at 0.083 h, 0.14 ± 0.02ΔΔ at 2 h, and 0.16 ± 0.03ΔΔ at 120 h (Fig. 5b). In contrast, the GABA-T level was less inhibited, with which was minimum by 0.53 ± 0.06 times at 0.083 h in Cer (Fig. 5c).
Note: 0.083 h, 2 h, and 120 h were the time points of AVM at the SC (0.0039 mg/L) (Ruan et al. 2013).
Analysis of mRNA expressions in peripheral tissues at the SC of AVM
According to Fig. 6, the GAD and GABA-T levels in the liver were both strongly inhibited at the SC of AVM (P < 0.01, Fig. 6). GAD65 and GAD67 levels were remarkably suppressed to 0.09 ± 0.01ΔΔ at 0.083 h (Fig. 6a) and 0.05 ± 0.01ΔΔ at 2 h (Fig. 6b). GABA-T genes were inhibited significantly, with minimum of which was 0.23 ± 0.02ΔΔ at 2 h in the liver (Fig. 6c), and expressions of GABA-T showed as a “high-low-high” trend. The GAD and GABA-T levels were also significantly downregulated in the kidney. In general, the volumes and the time-points which GAD65, GAD67, and GABA-T levels remarkably inhibited were 0.52 ± 0.05ΔΔ at 0.083 h (Fig. 7a), 0.06 ± 0.01ΔΔ at 0.083 h (Fig. 7b), and 0.26 ± 0.02ΔΔ at 2 h (Fig. 7c), respectively. Similarly, GAD and GABA-T levels in the muscle were also inhibited strongly. The largest variation range of GAD65, GAD67, and GABA-T were 0.20 ± 0.02ΔΔ × 10−2 (Fig. 8a), 0.57 ± 0.06ΔΔ × 10−1 (Fig. 8b), and 0.44 ± 0.02ΔΔ × 10−1 times greater (Fig. 8c) at 2 h, respectively.
Analysis of mRNA expressions at the LC50 of AVM
GAD65, GAD67, and GABA-T levels both in the brain and peripheral tissues were significantly downregulated (P < 0.01) at 96 h LC50 (0.039 mg/L). GAD65 level was inhibited significantly to 0.12 ± 0.01ΔΔ in Mer. Furthermore, GAD67 and GABA-T levels with minimum values were 0.19 ± 0.01ΔΔ and 0.64 ± 0.07ΔΔ in Med (Table 3). Compared to the liver, GAD65, GAD67, and GABA-T levels in the kidney were less inhibited. And the mRNA expressions of GAD65, GAD67, and GABA-T were 0.36 ± 0.06ΔΔ, 0.35 ± 0.04ΔΔ, and 0.91 ± 0.09ΔΔ, respectively. GAD and GABA-T levels in the muscle were inhibited strongly, where the relative expressions of GAD65, GAD67, and GABA-T were 0.0029 ± 0.0002ΔΔ, 0.062 ± 0.002ΔΔ, and 0.053 ± 0.005ΔΔ, respectively (Table 3).
Discussions
Effects of DIF on the mRNA expressions of GAD and GABA-T in crucian carp
It is generally believed that FQs antagonizes inhibitory neurotransmitter GABA, thereby increasing nerve excitability, leading to convulsions, epilepsy, and other adverse reactions (Motomura et al. 1991; Matsuo et al. 1998). GABA mediates the release of inhibitory synapses of neurons, which can reduce the hyperexcitability of neurons. Previous study found that crucian carp suffered from impatience and restlessness, body type tremors when treated with DIF (Ruan et al. 2014a). Meanwhile, it was also found in this paper that GAD65, GAD67, and GABA-T levels were significantly downregulated at 0.083 and 12 h in the brain after administrated with DIF at its SD (20 mg/kg b. W.), while GAD65, GAD67, and GABA-T levels were significantly upregulated at LD50 (2840 mg/kg b. W.) of DIF (P < 0.01, Fig. 1 and Table 2). However, GABA-T levels were significantly upregulated at 120 h in Tel and Cer after treated with DIF at its SD, which seemed to suggest that DIF could stimulate the overexpression of GABA-T to consume the GABA flux in the nerve center as an antagonistic inhibitor of GABA and enhance the convulsion effect of crucian carp. Moreover, the decreased GABA levels were also reported in the albino rat brain after intraperitoneal injection of FQS (Arafa et al. 2015). Similarly, GABA was continuously inhibited, resulting in epilepsy of old people after treated with FQS (Isaacson et al. 1993). These pieces of evidence suggested that the systemic neurotoxicity of crucian carp may be related to the upregulation of mRNA levels of GAD and GABA-T in various tissues treated with the lethal dose of DIF.
After the treatments at SD or LD50 of DIF, GABA-T level was significantly increased (P < 0.01) in the liver (Fig. 2 and Table 2). While GAD levels were of different expressions at the two doses, which may be lead to the accumulation of GABA in the liver for the reason of DIF. In addition, GAD and GABA-T levels showed time-concentration effect after administration with DIF at its SD or LD50 in the kidney (Fig. 4). This may suggested that low dose of DIF would inhibit GABA pathway, while high dose (or high residual) has opposite performance, the same as the effect of DIF on the central nervous system. This phenomenon may be a protective mechanism of stress resistance in crucian carp.
Effects of AVM on the mRNA expressions of GAD and GABA-T in crucian carp
GABA levels in organisms were determined by the dynamic balance between synthesis and catabolism and regulated by the level of GAD, precursor availability, and possibly GABA degradation (de Graaf et al. 2006). It has been reported that the neurotoxicity of AVM to organisms was due to its ability to trigger the opening of Cl− channels (Lasota and Dybas 1991). This process was irreversible and only occurred in invertebrates (Cornejo et al. 2014). In addition, the neurotoxicity of AVM was also reflected in the destruction of a large number of nerve cells (Shu et al. 2010). After been exposed to AVM at the SC (0.0039 mg/L) and LC50 (0.039 mg/L), the mRNA expressions of GAD and GABA-T both in the brain and peripheral tissues of crucian carp were inhibited significantly in this paper (P < 0.01, Figs. 4, 5, 6, 7, 8 and Table 3). This result indicated that the central nervous system was influenced by AVM in crucian carp. It was found that the mRNA levels of GAD65, GAD67, and GABA-T in the goldfish’s brain were downregulated after treatment with GABA receptor agonists (Martyniuk et al. 2007). Similar results were found in this paper.
Interestingly, GABA-T was inhibited to a much lower degree than that of GAD’s in the brain at LC50 of AVM. Based on previous research, the GAD level was much higher than that of GABA-T in the brain, which seemed to indicate that AVM would causes different expression of GAD and GABA-T (Ruan et al. 2014b). But on the contrary, GAD and GABA-T levels were extremely inhibited in the muscle after treated with AVM at the SC or at the LC50 (Fig. 8 and Table 3), which suggested that neuromuscular synthesis and metabolic rate of GABA were stagnant. This may lead to an imbalance in muscular nerve regulation, such as pathological convulsion of muscle. Similar findings were also found that the status of crucian carp was in physical imbalance and has a slower respiration rate after AVM treatments (Wang and Lu 2010). After been exposed to AVM, it was discovered that Japanese quails has a decrease of response to its natural enemies (de Faria et al. 2018b). Other paper found that AVM would cause twitching and keep exciting in bees; this may relate to the fact that AVM inhibits the expressions of GAD and GABA-T in the cerebellum (Zhao et al. 2014). Besides, deltamethrin and β-cypermethrin could downregulate GABA-T level in the cerebral cortex of rats, which resulting in an increase in GABA level (Ji et al. 2003; Han et al. 2014). All the evidences mentioned above suggested that AVM would break through the blood-brain barrier, which lead to the increase of GABA through affecting the mRNA expressions of GAD65, GAD67, and GABA-T in crucian carp’s nervous system.
Conclusion
The expressions of GAD65, GAD67, and GABA-T were all significantly downregulated at the SD of DIF except for the upregulated expression of GABA-T in the kidney and muscle tissues at 120 h, while the expressions of the three genes were significantly upregulated at the LD50 of DIF. In addition, the expressions of GAD65, GAD67, and GABA-T in various tissues of crucian carp were significantly downregulated both at the SC and LC50 of AVM.
References
Arafa N, Rawi MS, Mubarak SM, Abdullah S (2015) Exploration of the neurotoxicity of ciprofloxcin or gatifloxacin single dose in rat cortex and hippocampus. Afr J Pharm Pharmacol 9:65–73
Barrett MJ, Login IS (2009) Gemifloxacin-associated neurotoxicity presenting as encephalopathy. Ann Pharmacother 43:782–784
Chen LJ, Sun BH, Cao Y, Yao HD, Qu JP, Liu C, Xu SW, Li S (2014) The effects of avermectin on amino acid neurotransmitters and their receptors in the pigeon brain. Pestic Biochem Physiol 110:13–19
Chung I, Bown AW, Shelp BJ (1992) The production and efflux of 4-aminobutyrate in isolated mesophyll cells. Plant Physiol 99:659–664
Cornejo I, Andrini O, Niemeyer MI, Marabolí V, González-Nilo FD, Teulon J, Sepúlveda FV, Cid LP (2014) Identification and functional expression of a glutamate- and avermectin-gated chloride channel from Caligus rogercresseyi, a southern hemisphere sea louse affecting farmed fish. PLoS Pathog 10:e1004402
Da SW, Guimarães A, Montalvão MF, Mendes BO, Rodrigues A, Malafaia G (2018) The chronic exposure to abamectin causes spatial memory deficit and depressive behavior in mice. Chemosphere 194:523–533
de Faria D, Montalvão MF, de Souza JM, de Oliveira MB, Malafaia G, Rodrigues A (2018a) Analysis of various effects of abamectin on erythrocyte morphology in Japanese quails (Coturnix japonica). Environ Sci Pollut Res Int 25:2450–2456
de Faria D, Montalvão MF, Chagas TQ, Araújo A, Souza JM, Mendes BO, Rodrigues A, Malafaia G (2018b) Behavioral changes in Japanese quails exposed to predicted environmentally relevant abamectin concentrations. Sci Total Environ 636:1553–1564
de Graaf RA, Patel AB, Rothman DL, Behar KL (2006) Acute regulation of steady-state GABA levels following GABA-transaminase inhibition in rat cerebral cortex. Neurochem Int 48:508–514
Demetrious JS (2018) Spontaneous cervical artery dissection: a fluoroquinolone induced connective tissue disorder? Chiropr Man Therap 26:22
Grill MF, Maganti RK (2011) Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol 72:381–393
Guiol C, Ledoussal C, Surgé JM (1993) Pharmacological properties of a new fluoroquinolone on the central nervous system in rodents. Arzneimittelforschung 43:56–60
Han Y, Cao D, Li X, Zhang R, Yu F, Ren Y, An L (2014) Attenuation of γ-aminobutyric acid (GABA) transaminase activity contributes to GABA increase in the cerebral cortex of mice exposed to β-cypermethrin. Hum Exp Toxicol 33:317–324
Isaacson SH, Carr J, Rowan AJ (1993) Ciprofloxacin-induced complex partial status epilepticus manifesting as an acute confusional state. Neurology 43:1619–1621
Ji ZY, Shi N, Wang SQ, Dong J, Chen MS (2003) Effects of pyrethroids on the activity of gamma-aminobutyric acid transferase in rat brain. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 21:197–199
Kudryavtsev DS, Shelukhina IV, Son LV, Ojomoko LO, Kryukova EV, Lyukmanova EN, Zhmak MN, Dolgikh DA, Ivanov IA, Kasheverov IE, Starkov VG, Ramerstorfer J, Sieghart W, Tsetlin VI, Utkin YN (2015) Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors. J Biol Chem 290:22747–22758
Lasota JA, Dybas RA (1991) Avermectins, a novel class of compounds: implications for use in arthropod pest control. Annu Rev Entomol 36:91–117
Li M, You TZ, Zhu WJ, Qu JP, Liu C, Zhao B, Xu SW, Li S (2013) Antioxidant response and histopathological changes in brain tissue of pigeon exposed to avermectin. Ecotoxicology 22:1241–1254
Martyniuk CJ, Chang JP, Trudeau VL (2007) The effects of GABA agonists on glutamic acid decarboxylase, GABA-transaminase, activin, salmon gonadotrophin-releasing hormone and tyrosine hydroxylase mRNA in the goldfish (Carassius auratus) neuroendocrine brain. J Neuroendocrinol 19:390–396
Matsuo H, Ryu M, Nagata A, Uchida T, Kawakami JI, Yamamoto K, Iga T, Sawada Y (1998) Neurotoxicodynamics of the interaction between ciprofloxacin and foscarnet in mice. Antimicrob Agents Chemother 42:691–694
Motomura M, Kataoka Y, Takeo G, Shibayama K, Ohishi K, Nakamura T, Niwa M, Tsujihata M, Nagataki S (1991) Hippocampus and frontal cortex are the potential mediatory sites for convulsions induced by new quinolones and non-steroidal anti-inflammatory drugs. Int J Clin Pharmacol Ther Toxicol 29:223–227
Nasr HM, El-Demerdash FM, El-Nagar WA (2016) Neuro and renal toxicity induced by chlorpyrifos and abamectin in rats: toxicity of insecticide mixture. Environ Sci Pollut Res Int 23:1852–1859
Nasreen Z, Jameel T, Hasan A, Parveen N, Sadasivudu B (2012) Glutamate decarboxylase and GABA aminotransferase levels in different regions of rat brain on the onset of Leptazol induced convulsions. Neurochem Res 37:202–204
Novelli A, Vieira BH, Braun AS, Mendes LB, Daam MA, Espíndola EL (2016) Impact of runoff water from an experimental agricultural field applied with Vertimec® 18EC (abamectin) on the survival, growth and gill morphology of zebrafish juveniles. Chemosphere 144:1408–1414
Owens RJ, Ambrose PG (2005) Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 41(Suppl 2):S144–S157
Ruan J, Hu K, Yang X (2013) Permeability of avermectin to blood-brain barrier and tissue residue in allogynogenetic crucian carp. Journal of Fishery Sciences of China 20:1032–1038
Ruan J, Hu K, Zhang H, Wang Y, Zhou A, Zhao Y, Yang X (2014a) Distribution and quantitative detection of GABAA receptor in Carassius auratus gibelio. Fish Physiol Biochem 40:1301–1311
Ruan J, Hu K, Yang X, Zhang H, Wang Y, Zhou A, Zhao Y (2014b) Permeability and elimination of difloxacin to blood-brain barrier in allogynogenetic crucian carp. Acta Hydrobiologica Sinica 38:272–278
Sánchez-Borzone ME, Marin LD, García DA (2017) Effects of insecticidal ketones present in mint plants on GABA(A) receptor from mammalian neurons. Pharmacogn Mag 13:114–117
Shu L, Yali C, Min W, Shi-wen X, Jun-jie W (2010) Effect of avermectin on nerve cell apoptosis and nitric oxide level in pigeons. Chinese Journal of Animal and Veterinary Sciences 41:347–352
Struzyńska L, Sulkowski G (2004) Relationships between glutamine, glutamate, and GABA in nerve endings under Pb-toxicity conditions. J Inorg Biochem 98:951–958
Vasconcelos AM, Daam MA, Dos SL, Sanches AL, Araújo CV, Espíndola EL (2016) Acute and chronic sensitivity, avoidance behavior and sensitive life stages of bullfrog tadpoles exposed to the biopesticide abamectin. Ecotoxicology 25:500–509
Wang X, Lu H (2010) Acute toxicity and histopathology of abamectin in Carassius auratus gibelio. Journal of Dalian Ocean University 25:66–70
Weichert FG, Floeter C, Meza AA, Kammann U (2017) Assessing the ecotoxicity of potentially neurotoxic substances - evaluation of a behavioural parameter in the embryogenesis of Danio rerio. Chemosphere 186:43–50
Wood JD, Kurylo E, Newstead JD (1978) Aminooxyacetic acid induced changes in gamma-aminobutyrate metabolism at the subcellular level. Can J Biochem 56:667–672
Xi J, Liu J, He S, Shen W, Wei C, Li K, Zhang Y, Yue J, Yang Z (2019) Effects of norfloxacin exposure on neurodevelopment of zebrafish (Danio rerio) embryos. Neurotoxicology 72:85–94
Xiao C, Han Y, Liu Y, Zhang J, Hu C (2018) Relationship between fluoroquinolone structure and neurotoxicity revealed by zebrafish neurobehavior. Chem Res Toxicol 31:238–250
Zhao YL, W. Y. G. J (2014) Acute toxicity and risk assessment of avermectin and its mixture on honeybees in Hainan. Chinese Journal of Environmental Entomology, 36, 744-748+704
Funding
This work was supported by the National Natural Science Foundation of China (No. 31860735) and the Science and Technology Support Project of Jiangxi Province (No. 20151BBF60056).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Fan Zhang and Kun Hu are co-first authors.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Zhang, F., Hu, K., Huang, J. et al. Effects of two kinds of fishery drugs on the expressions of GAD and GABA-T mRNA in crucian carp (Carassius auratus gibelio). Fish Physiol Biochem 46, 1965–1973 (2020). https://doi.org/10.1007/s10695-020-00847-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-020-00847-z