Regulation of BTB (POZ) Structural Domain 6b by MicroRNA-222b in Zebrafish Embryos after Exposure to Di(2-ethylhexyl)phthalate at Low Concentrations.

Di-(2-ethylhexyl) phthalate (DEHP) is a sort of endocrine disruptor that induces abnormal physiological and biochemical activities such as epigenetic alterations, apoptosis, and oxidative stress. MicroRNAs (miRNAs) are a class of short noncoding RNAs that may regulate the expression of many protein-coding genes when organisms are exposed to environmental chemicals. miR-222b is a differentially expressed miRNA after DEHP exposure. miRNA-mRNA prediction suggested that BTB (POZ) structural domain 6b (BTBD6B) might be a target mRNA of miR-222b, and DEHP exposure altered its expression. However, the correlation between miR-222b and BTBD6B has not been experimentally confirmed. The aim of this study was to investigate the regulation of BTBD6B by miR-222b in zebrafish embryos under the effect of low concentration of DEHP. Dual fluorescent protein assays and dual luciferase reporter gene assays confirmed the interaction between miR-222b and the 3'-untranslated region (3'-UTR) of BTBD6B. Ectopic expression assays showed that miR-222b could negatively regulate BTBD6B in ZF4 cells. However, the relative expression of miR-222b and BTBD6B was significantly higher at both transcriptional and post-transcriptional levels in zebrafish embryos exposed to low concentrations of DEHP. The results of this study improved our understanding of the molecular mechanism of DEHP exposure toxicity. It identified that the aberrant expression of miR-222b/BTBD6B may be one of the mechanisms of DEHP toxicity, which can provide a theoretical reference and scientific basis for environmental management and biological health risk assessment.

Sex comparison of oxidative stress, mitochondrial dysfunction, and apoptosis triggers induced by single-dose Abamectin in albino rats.

Abamectin (AB) is widely used in agriculture and has been employed as an insecticide, nematicide, and livestock pest control agent. However, it may also pose a serious threat to mammals. The primary purpose of this research was to compare the sex variations between male and female rats during exposure and to assess the risk of toxicity of abamectin, which are still largely unknown. The twenty albino rats were divided randomly into four groups (n = 5): 1) the male control group; 2) the male treatment group treated with AB (1 mg/kg B.W.); 3) the female control group; and 4) the female treatment group treated with AB (1 mg/kg B.W.). AB administration caused a drop in body weight in females more than males with showing oxidative stress in both sexes of animals, as characterized by an increase in MDA content and a decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Reported sex-specific effects suggested that females are more susceptible from males in brain tissues for alteration of antioxidant markers while females' liver and kidney tissues showed more level of lipid peroxidation than males. In addition, mitochondrial dysfunction was associated with a significant decrease in NADH dehydrogenase (Complex I) and a significant decrease in mitochondrial ATPase, which led to apoptosis and histopathological alterations in the targeted tissues, indicating that females are higher sensitive than males to these biological events. In brief, the results of this study led to female rats are generally more sensitive than male rats to neurobehavioral and hepatic complications associated with abamectin treatment. Further evaluation should be performed to determine the adverse outcome pathways involved and to determine the effects of sex on improving the risk assessment of abamectin in both sexes.

MicroRNA-375 Mediated Regulation on Pre-mRNA Processing Factor 3 in Zebrafish Embryos Exposed to Di-(2-ethylhexyl)phthalate at Low Concentrations.

Di-(2-ethylhexyl)phthalate (DEHP) is an endocrine-disrupting chemical (EDC) that induces epigenetic alterations, apoptosis, and oxidative stress after biological exposure. MicroRNAs (miRNAs) are a class of small noncoding RNAs with many regulatory functions and play a role in organisms exposed to environmental chemicals. miRNA-mRNA prediction indicated that pre-mRNA processing factor 3 (PRPF3) is a likely target mRNA for miR-375 whose expression is altered by DEHP exposure. However, the interrelation between miR-375 and PRPF3 has not yet been confirmed experimentally. This study aimed to investigate the effects of DEHP on miR-375 and PRPF3 in zebrafish. The expression of miR-375 was downregulated, whereas PRPF3 was upregulated at both transcriptional and post-transcriptional levels upon stimulation with DEHP. The interaction between miR-375 and the 3'-untranslated region (3'-UTR) of PRPF3 was confirmed by a dual fluorescent protein assay and a dual luciferase reporter gene assay. The expression of PRPF3 at both transcriptional and post-transcriptional levels was reduced in ZF4 cells when transfected with a miR-375 mimic but increased when transfected with a miR-375 inhibitor. The results improved our understanding of molecular mechanisms of toxicity upon DEHP exposure and presented miR-375 as a potential novel toxicological biomarker for chemical exposure.

Imidacloprid Induces Neurotoxicity in Albino Male Rats by Inhibiting Acetylcholinesterase Activity, Altering Antioxidant Status, and Primary DNA Damage.

Imidacloprid (IMI) is a neonicotinoid insecticide used worldwide, either alone or in combination with other pesticides. The goal of this study was to assess the effects of IMI on the central nervous system of rats and its mechanism of oxidative stress-induced DNA damage by oxidant/antioxidant parameters. Fifteen male rats, divided into three groups, were used: the first group received 5 ml/kg body weight corn oil as a control, the second received a high oral dose of IMI (45 mg/kg body weight), while the third received a low dose (22 mg/kg body weight). After 28 days, acetylcholinesterase (AChE) activity, oxidative stress markers, histopathological alterations, and DNA damage were examined in the brains of these rats. The AChE activities decreased significantly after IMI exposure, reaching 2.45 and 2.75 nmol/min/mg protein in high dose and low dose, respectively, compared to the control group (3.75 nmol/g tissues), while the concentration of malondialdehyde MDA increased significantly (29.28 and 23.92 nmol/g tissues) vs. the control group (19.28 nmol/g tissues). The antioxidant status parameters such as reduced glutathione (GSH) content was 13.77 and 17.63 nmol/g, catalase (CAT) activity was 22.56 and 26.65 µmol/min/g, and superoxide dismutase (SOD) activity was 6.66 and 7.23 µmol/min/g in both doses against the control group (21.37 nmol/g, 30.67 µmol/min/g, 11.76 µmol/min/g), respectively, and histopathological changes in the brain tissues were observed. More in vivo research using epigenetic methods is needed to determine the ability of IMI and its metabolites to cause neurotoxicity and DNA lesions in mammalian brains.

Protective action of polysaccharides from Laurencia papillose (Rhodophyta) against imidacloprid induced genotoxicity and oxidative stress in male albino rats.

Imidacloprid (IMI), the main component of neonicotinoid insecticides, promotes oxidative stress and genotoxicity in mammals. The aim of this experiment is to assess oxidative stress in liver cells and genotoxicity of erythrocytes for rats exposed to sub-lethal doses of IMI and the protective effects for Rhodophyta as antioxidant material versus imidacloprid. A total of 30 adult male albino rats (average body weight, 190-200 g) were divided into six groups (n=5) as follows: group 1 served as the control, group 2 received 200 mg/kg red algae, group 3 received 45 mg/kg IMI (high-dose group), group 4 received 22.5 mg/kg IMI (low-dose group), group 5 received 200 mg/kg red algae +45 mg/kg IMI, and group 6 received 200 mg/kg red algae +22.5 mg/kg IMI. After 28 d of treatment, the antioxidant activity of the crude extract of red algae was assessed in terms of free radical scavenging activity and found to be higher in TCA (75.57%) followed by DPPH (50.08%) at concentration 100 µg extract and a significant increase in lipid peroxidation and reductions in glutathione were observed in liver cells were intoxicated with high and low doses of IMI. Moreover decreases in catalase and glutathione peroxidase parameters in same previous groups which indicated oxidative stress. In addition significant increases in micronucleus frequency (MN) in the bone marrow of the rats as a genotoxicity marker which indicated DNA damage in erythrocytes cells with alterations in the histopathology of liver cells were also noted such as necrosis, inflammatory cells, infiltration, and necrobiotic changes. Whereas Rhodophyta succeeded in alleviation the oxidative damage and genotoxicity induced by the insecticide. In conclusion, IMI demonstrates hazardous effects, such as alterations in antioxidant status and mutagenicity of erythrocytes and polysaccharides from Rhodophyta has good antioxidant activity in vivo model systems against imidacloprid.

Ameliorative effects of the phytochemicals in dates (Phoenix dactylifera) against the toxicological changes induced by fipronil in male albino rats.

Scientific evidence has shown that fipronil induces oxidative stress and genotoxicity. Our study aimed to evaluate the potential oxidation in redox parameters and DNA, as well as determine the protective effect of date extract of increasing resistance to cellular damage. 30 Male albino rats were divided into six groups ( n = 5): 1) control group; 2) treatment group with date extract (1 g/kg B.W.); 3) treatment group with 1/20 LD50 of fipronil; 4) treatment group with 1/40 LD50 of fipronil; 5) treatment group with 1/20 LD50 of fipronil + 1 g/kg date extract; and 6) treatment group with 1/40 LD50 of fipronil + 1 g/kg dates extract. Date extract showed a high content of phenolic compounds and antioxidant properties. Fipronil increased 8-hydroxy-2-deoxyguanosine levels and lipid peroxidation by malondialdehyde but decreased the total antioxidant capacity in plasma. Moreover, glutathione, catalase, and superoxide dismutase levels in the liver and kidney decreased, along with histopathological abnormalities. Additionally, tail moment parameters of liver DNA and micronucleus frequencies in the bone marrow increased. This study showed that fipronil-induced various health hazards in vivo, whereas date extract alleviated the said toxicological effects. However, date extract failed to reduce genotoxicity.