## 4 Discussion  
Cd was found to induce reactive oxygen species (ROS) production and oxidative stress in zebrafish at a nonlethal concentration, which can enhance SOD activity to eliminate the ROS radicals [38]. When exposed to CBZ, the SOD activity in female zebrafish increased slightly in comparison with the control group. Similar trends of SOD activity displayed in previous studies neutralized the impact of increased ROS generation in rainbow trout after chronic CBZ treatment [39]. When exposed to the combination of Cd and CBZ, the SOD activity increased sharply in the 0.1 ug/L Cd + 0.1 ug/L CBZ group, even higher than in the 0.1 ug/L Cd group. Interestingly, the increasing combination concentration did not lead to the continual increase of SOD activity. [PERSON] et al. studied the effects of single and combined exposure of CBZ and Cd of _R. philipipinarum_, and found that SOD activity increased when exposed to the 0.5 ug/L Cd + 1.0 ug/L CBZ compared to the control group, but was lower than the single-exposed Cd (0.5 ug/L) and CBZ (1.0 ug/L) groups, respectively [35]. In that research, no further combination concentrations were investigated. Some other studies investigated the effects induced by the coexposure of Cd and organic pollutants including PPCPs, showing that Cd effects on the aquatic organisms may depend on the type of organic pollutants present in aquatic systems [34; 37; 40]. Figure 4: **(A)** Vitellogenin (VTG) content and **(B)** Estradiol (E2) content in female fish after ten -days of exposure to Cd, CBZ, and Cd + CBZ. The results of one-way ANOVA are indicated at the significance levels * \(p\) < 0.05, **_p_ < 0.01, and ***_p_ < 0.001. Figure 3: Lactate dehydrogenase (LDH) activity in female fish after ten days of exposure to Cd, CBZ, and Cd + CBZ. The results of one-way ANOVA are indicated at the significance levels * \(p\) < 0.05, **_p_ < 0.01, and ***_p_ < 0.001. CAT activity was reduced by Cd exposure, which may be because it was consumed by the degradation of the hydrogen peroxide produced during the superoxide disproportionation under oxidative stress [39; 41]. CAT activity in mice also had similar tendencies after Cd exposure for seven days [42]. CAT activity was suppressed in the CBZ exposure group at a low concentration, but was induced in the group at high concentration. The data from the combined treatments suggests that the combined exposure of Cd and CBZ exerted weaker effects on CAT activity compared to single Cd exposure, indicating that the presence of the CBZ attenuated the Cd effects. As previously mentioned, the combined effects of Cd with CBZ in zebrafish have not been studied. However, some researchers evaluated the effects of PPCPs combined with Cd or other metals in bivalves. For example, [PERSON] et al. observed that weaker effects on CAT activity in _R. philipipinarum_ were exerted by combined exposure of 0.5 ug/L Cd + 1.0 ug/L CBZ than by single exposure of 0.5 ug/L Cd [35]. [PERSON] et al. observed that Cu combined with PPCPs (ibuprofen, diclofenac, and fluoxetine) exerted weaker effects on CAT activity in mussel gills than single exposure by PPCPs [26]. AChE is a good candidate that is responsible for the hydrolysis of the neurotransmitter acetylcholine, which plays an important role in the nervous system [43]. AChE could be a target for pollutants, resulting in the inhibition of its activity, failure of synaptic transmission, and muscle overstimulation [44; 45]. Thus, AChE activity has been used as a biomarker to evaluate the neurotoxicity of pollutants. [PERSON] et al. studied the AChE activity in zebrafish gill, suggesting that Cd can inhibit the AChE activity in zebrafish: the higher the Cd concentration; the higher the inhibition degree of AChE activity [46]. This result was similar to the behavior response based on behavior strength, suggesting that inhibition exerted by Cd can induce a decrease of swimming behavior, loss of coordination, and other kinds of behavior change of zebrafish [47]. [PERSON] et al.