## 4 Discussion
### Histological Alterations Discussion  
The presence of vacuolated hepatocytes in the patulin-treated group is confirmed by a study on rats [41]. Vacuolization is considered a side effect of cytotoxic factors and a mechanism that can reduce stress and increase the survival of the cells [42]. Hepatocyte damage and loss of cell outline has also been observed in mice, after 2 weeks of patulin exposure [43]. The hepatocytes of the patulin-treated group showed hydrop and lipid dystrophy. Additionally, in the case of mice, patulin exposure led to fatty degeneration [44], but there is a difference between the hyperhydration observed in zebrafish hepatocytes and mice hepatocytes, which had granular cytoplasm [43]. While in the case of patulin-treated rats [41] or mice [44], hepatocyte necrosis, sinusoids dilation/irregularities or nuclear abnormalities were observed, these alterations were absent in the liver of patulin-treated zebrafish. Another difference is that Lymphocyte infiltration in the liver of patulin-exposed rats and mice [45] was absent in patulin-treated zebrafish. Following the administration of a diet containing 0.5-2% kojic acid for 26 weeks, a carcinogenic effect (hepatocellular adenoma) was observed on the liver of mice. Cellular alteration, necrosis and inflammatory processes have been observed [46]. These effects have also been observed in mice exposed to kojic acid for 26 weeks [47]. Long-term exposure (13 weeks) will increase liver mass [48]. The exposure to kojic acid for 4 weeks (through diet--2%) did not cause noticeable histological alterations in the liver [49], which shows that mice are less sensitive to the effects of kojic acid compared to zebrafish. Rats' exposure to kojic acid (2% of diet, 55 weeks) caused hepatocytes vacuolation, cell necrosis (isolated cases), granulomas, and bile ducts proliferation [50]. Human liver tumor cells also suffer from nuclear alterations after exposure to high doses (6-8 g/L) of kojic acid: the increase in the frequency of micronucleeli isaccompanied by a severe toxic alteration of liver cells [51]. The absence of the inflammatory component shows that, in the liver, the immune system of zebrafish has not been activated following short-term exposure to kojic acid, unlike in rodents. At all the applied doses, liver damage will lead to the alteration of the metabolism, acid-base balance, thermoregulation, blood clotting, bile, and enzyme synthesis. Due to cell destruction, liver enzymes (transaminases, alkaline phosphatase, gamma-glutamyltransferase, lactate dehydrogenase) will reach the bloodstream. Altering bile secretion will reduce the digestive capacity of lipids. Additionally, the antitoxic function of the liver will be affected: toxic elements in water and food, metabolic products of intestinal bacteria will reach the bloodstream causing severe intoxations. The apoptosis of the renal cells was absent, in contrast with a study on mice [52]. The similarity between the effects on zebrafish and rodents is sustained by the morphological alterations of the glomeruli and renal tubules shown in the case of patulin-exposed zebrafish embryos [53] and mice [44]. In the case of zebrafish embryos, the morphological alterations of the glomeruli are followed by a reduction of the filtration rate [53], thus we can make the assumption that glomeruli degeneration also alters the filtration rate of the adult zebrafish. Interstitial capillaries of the patulin-treated zebrafish are overloaded with erythrocytes, thus leading to a medium congestion, while kidney of the patulin treated mammals showed capillary lesions [54; 55; 56] and hemorrhagic lesions of the kidney [44]. The patulin-treated zebrafish exhibit a renal inflammatory process caused by monocyte infiltration, while in patulin-treated rats the inflammation was caused by a lymphocyte infiltration [45]. Additionally, in the kidney of patulin-exposed mice, there was observed an inflammatory cell infiltration [44].