Molecular Evolution and Functional Divergence of the Cytochrome P450 3 (CYP3) Family in Actinopterygii (Ray-Finned Fish)

The cytochrome P450 (CYP) superfamily is a multifunctional hemethiolate enzyme that is widely distributed from Bacteria to Eukarya. The CYP3 family contains mainly the four subfamilies CYP3A, CYP3B, CYP3C and CYP3D in vertebrates; however, only the Actinopterygii (ray-finned fish) have all four subfamilies and detailed understanding of the evolutionary relationship of Actinopterygii CYP3 family members would be valuable.Phylogenetic relationships were constructed to trace the evolutionary history of the Actinopterygii CYP3 family genes. Selection analysis, relative rate tests and functional divergence analysis were combined to interpret the relationship of the site-specific evolution and functional divergence in the Actinopterygii CYP3 family. The results showed that the four CYP3 subfamilies in Actinopterygii might be formed by gene duplication. The first gene duplication event was responsible for divergence of the CYP3B/C clusters from ancient CYP3 before the origin of the Actinopterygii, which corresponded to the fish-specific whole genome duplication (WGD). Tandem repeat duplication in each of the homologue clusters produced stable CYP3B, CYP3C, CYP3A and CYP3D subfamilies. Acceleration of asymmetric evolutionary rates and purifying selection together were the main force for the production of new subfamilies and functional divergence in the new subset after gene duplication, whereas positive selection was detected only in the retained CYP3A subfamily. Furthermore, nearly half of the functional divergence sites appear to be related to substrate recognition, which suggests that site-specific evolution is closely related with functional divergence in the Actinopterygii CYP3 family.The split of fish-specific CYP3 subfamilies was related to the fish-specific WGD, and site-specific acceleration of asymmetric evolutionary rates and purifying selection was the main force for the origin of the new subfamilies and functional divergence in the new subset after gene duplication. Site-specific evolution in substrate recognition was related to functional divergence in the Actinopterygii CYP3 family

The toxicity and adverse effects of selected drugs in animals - overview

Therapeutic products quite often are causes of poisoning in both small and large animals. Drug poisonings in animals occur commonly due to off-label use of medicines, wrong dosage, negligence, accidental ingestion and deliberate poisonings. Toxicity of veterinary drugs may become evident also in therapeutic doses when adverse effects may occur. The aim of this review is to inform veterinary specialists about both veterinary and human drugs, specifically antiparasitics, non-steroidal anti-inflammatory drugs and other medicinal substances, which are most often reported to cause acute poisonings or adverse reactions in animals and to contribute to their broader knowledge and more accurate use of medicines, improving instructions to the animal owners and, hopefully, decrease the incidence of drug poisonings in animals

Nuclear factor-kB and nitric oxide synthases in red blood cells: Good or bad in obesity? a preliminary study

Emerging evidence suggests that red blood cells (RBCs) are involved in many functions essential for life. Nuclear factor-kB (NF-kB), nitric oxide synthases (inducible nitric oxide synthase-iNOS-, endothelial nitric oxide synthase-eNOS-) and interleukin-1β (-IL-1β-) are all proteins that have been identified in RBCs. In nucleated cells, such as white blood cells (WBCs), these proteins have well investigated roles, linked to stress and inflammation. It is not the same in erythrocytes. For this reason, we considered obese patients for studying the morphology of RBCs. We studied a possible correlation between their morphological changes and several protein expressions. Moreover, we compared the results about the aforementioned proteins and antioxidant markers with those obtained in WBCs from healthy and obese patients before and after omega-3 polyunsaturated fatty acid supplementation. This latter scientific point is important in order to determine whether there are differences in the expression of nucleated and anucleated cells. The morphology of RBCs changed in obese patients, but it is significantly restored after six weeks of supplementation. The expression of antioxidant enzymes changed in RBCs and WBCs in obesity but all proteins restore their positivity after supplementation. We found that: the presence of NF-kB, antioxidant enzymes and eNOS in healthy RBCs could indicate a role of these proteins as regulators of cellular metabolism; obese WBCs showed a higher NF-kB, iNOS and IL-1β positivity, whereas eNOS presence did not significantly change in these cells. We tried to explain the different positivity of NF-kB, proposing a dual role for this protein, as prolifespan and as proinflammatory processes, depending on examined cells. In conclusion, we have considered the literature that focuses on the omega6/omega-3 ratio. The ratio changed from the past, especially in people whose diet is strongly westernized worsening the state of health of the patient and leading to an higher incidence of obesity. Our study hypothesizes that the supplementation could help to restore the correct ratio

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio)

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 ± 9.8 mg/L in juvenile Danio rerio, and 6.11 ± 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P<0.05) in embryonic stages compared to the juvenile fish

Mercury distribution in the great cormorant (Phalacrocorax carbo) from the Krogulna ponds and Nysa Kłodzka River (Poland)

Mercury belongs among the highly hazardous substances present in the environment and represents a great health risk for many animals including predatory and piscivorous birds. The aim of this study was to assess the total mercury content in the main detoxifying organs (liver and kidney) and in the muscles of adult great cormorants (Phalacrocorax carbo) caught at two localities (the Krogulna ponds and the Nysa Kłodzka River) in southern Poland. The aim was to compare the locality with the iron ore mining history (the Krogulna ponds) with a site without such load (the Nysa Kłodzka River). The total mercury content in the great cormorants decreases as follows: kidneys &gt; liver &gt; muscle in both monitored localities and significantly differs between the localities. The average mercury content varied from 0.58 ± 0.38 mg/kg (muscle) to 1.39 ± 1.42 mg/kg (kidney) in the cormorant from the Krogulna ponds and from 1.09 ± 0.40 mg/kg (muscle) to 3.12 ± 1.55 mg/kg (kidney) in the cormorant from the Nysa Kłodzka River. The accumulation of mercury does not correlate with the mining history as it was higher at the Nysa Kłodzka River, but it is probably influenced by the different fish stocks in these two localities (omnivorous fish in the Krogulna ponds versus predatory fish in the Nysa Kłodzka River)