Rosmarinus officinalis L. ameliorates titanium dioxide nanoparticles and induced some toxic effects in rats' blood.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used as a white pigment in food and drugs. The most important route of human exposure to TiO2 is through food and drug products containing TiO2 additives. This study investigates the efficacy of an oral traditional use of rosemary extract in ameliorating some toxic effects induced on blood of TiO2 NP-intoxicated rats. Rats were given rosemary extract via intragastric administration 1 h before the intragastric administration of 100 mg/kg/day TiO2 NPs (10 nm) for 60 days. TiO2 NPs significantly increased serum cholesterol, glucose, and triglyceride levels of rats. They also induced significant oxidative stress and inflammatory and caused DNA damage in peripheral blood leukocytes. The rosemary extract appears to have a significant protective effect by lowering glucose level properties, restoring the lipid profile and showing an antioxidative, anti-inflammatory, and antigenotoxic properties against TiO2 NPs toxicity. In conclusion, this study gives an encouraging scientific basis for consumers of rosemary leaves to keep on with this culinary habit.

The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity in several applications such as food colorants, drug additives, biomedical ceramic, and implanted biomaterials. Research on the neurobiological response to orally administered TiO2 NPs is still limited. In our study, we investigate the effects of anatase TiO2 NPs on the brain of Wistar rats after oral intake. After daily intragastric administration of anatase TiO2 NPs (5-10 nm) at 0, 50, 100, and 200 mg/kg body weight (BW) for 60 days, the coefficient of the brain, acethylcholinesterase (AChE) activities, the level of interleukin 6 (IL-6), and the expression of glial fibrillary acidic protein (GFAP) were assessed to quantify the brain damage. The results showed that high-dose anatase TiO2 NPs could induce a downregulated level of AChE activities and showed an increase in plasmatic IL-6 level as compared to the control group accompanied by a dose-dependent decrease inter-doses, associated to an increase in the cerebral IL-6 level as a response to a local inflammation in brain. Furthermore, we observed elevated levels of immunoreactivity to GFAP in rat cerebral cortex. We concluded that oral intake of anatase TiO2 NPs can induce neuroinflammation and could be neurotoxic and hazardous to health.

Hematological, biochemical, and toxicopathic effects of subchronic acetamiprid toxicity in Wistar rats.

Acetamiprid is one of the most widely used neonicotinoids. This study investigates toxic effects of repeated oral administration of three doses of acetamiprid (1/20, 1/10, and 1/5 of LD50) during 60 days. For this, male Wistar rats were divided into four different groups. Hematological, biochemical, and toxicopathic effects of acetamiprid were evaluated. According to the results, a significant decrease in the body weight gain at the highest dose 1/5 of LD50 of acetamiprid was noticed. An increase in the relative liver weight was also observed at this dose level. The hematological constituents were affected. A significant decrease in RBC, HGB, and HCT in rats treated with higher doses of acetamiprid (1/10 and 1/5 of LD50) was noted. However, a significant increase in WBC and PLT were observed at the same doses. Furthermore, acetamiprid induced liver toxicity measured by the increased activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphates (ALPs), and lactate dehydrogenase (LDH) which may be due to the loss of hepatic membrane architecture and hepatocellular damage. In addition, exposure to acetamiprid resulted in a significant decrease in the levels of superoxide dismutase and catalase activities (p ≤ 0.01) with concomitant increase in lipid peroxidation in rat liver. These findings highlight the subchronic hepatotoxicity of acetamiprid.

Histopathological and genotoxic effects of chlorpyrifos in rats.

This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

Circadian variation of cytotoxicity and genotoxicity induced by an immunosuppressive agent "Mycophenolate Mofetil" in rats.

Immunosuppressive drugs such as Mycophenolate Mofetil (MMF) are used to suppress the immune system activity in transplant patients and reduce the risk of organ rejection. The present study investigates whether the potential cytotoxicity and genotoxicity varied according to MMF dosing-time in Wistar Rat. A potentially toxic MMF dose (300 mg/kg) was acutely administered by the i.p. route in rats at four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO). Rats were sacrificed 3 days following injection, blood and bone marrow were removed for determination of cytotoxicity and genotoxicity analysis. The genotoxic effect of this pro-drug was investigated using the comet assay and the micronucleus test. Hematological changes were also evaluated according to circadian dosing time. MMF treatment induced a significant decrease at 7 HALO in red blood cells, in the hemoglobin rate and in white blood cells. These parameters followed a circadian rhythm in controls or in treated rats with an acrophase located at the end of the light-rest phase. A significant, thrombocytopenia was observed according to MMF circadian dosing time. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, poikilocytotic in red cells and hypersegmented neutrophil nuclei were observed with MMF treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow; the comet assay showed significant DNA damage. This damage varied according to circadian MMF dosing time. The injection of MMF in the middle of the dark-activity phase produced a very mild hematological toxicity and low genotoxicity. Conversely, it induced maximum hematological toxicity and genotoxicity when the administration occurred in the middle of the light-rest phase, which is physiologically analogous to the end of the activity of the diurnal phase in human patients.

Toxicopathic changes and genotoxic effects in liver of rat following exposure to diazinon.

In general, people may come in contact with mixtures of insecticides through domestic use, consumption of contaminated food or drinks, and/or living close to treated areas. We analyzed the toxic effects of diazinon on histological structure of liver and hematological parameters in male rats. DNA-damaging potential of diazinon was also investigated using the comet assay in blood cells and the micronucleus test in bone marrow. Two groups of six male rats orally received different amounts of diazinon: 1/50 and 1/25 LD 50 for 4 weeks (5 day/week). The present study showed that diazinon caused hypertrophy of sinusoids, central vein, and portal triad, in addition to the formation of oedema, vacuoles, hemorrhage, necrosis, and lymphoid infiltration in rats' liver. A significant decrease in red blood cells, hemoglobin, hematocrite levels, and platelet counts was observed in the treated groups. However, the white blood cell count increased. Micronucleus test results revealed aneugenic effects of diazinon. Furthermore, we noticed an increase in comet tail length in treated groups. So, the comet assay confirmed the genotoxic potential of diazinon in vivo. On the assumption that all alterations observed in rats could be observed in human, it is necessary to raise the awareness about the health risk posed by this insecticide.

Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity. We investigated the hematological effects and genotoxicity of anatase TiO2 NPs following sub-chronic oral gavage treatment. TiO2-NPs were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Wistar rats were treated with anatase TiO2 NPs by intragastric administration for 60 days. Hematological analysis showed a significant decrease in RBC and HCT and a significant increase in MCV, PLT, MPV and WBC at higher doses. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, and hyper-segmented neutrophil nuclei were observed with TiO2 NPs treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow at 100 and 200mg/kg bw; the comet assay showed significant DNA damage at the same doses.

Antiproliferative, antioxidant, and antimutagenic activities of flavonoid-enriched extracts from (Tunisian) Rhamnus alaternus L.: combination with the phytochemical composition.

A pronounced antiproliferative effect on human leukemia K562 cells was shown with flavonoid-enriched extracts from Rhamnus alaternus roots and leaves, with, respectively, IC(50) values of 165 and 210.73 microg/mL. High DPPH radical-scavenging activity (7.21 and 18.84 microg/mL, respectively) and antioxidative effects using the xanthine oxidase assay (IC(50) values of 83.33 and 103.96 microg/mL, respectively) were detected in the presence of the two tested extracts. Although no mutagenic effect was observed when using the Salmonella typhimurium assay system with TA1535 and TA100 strains, the two tested extracts exhibited a high-level protection toward the direct mutagen, sodium azide-induced response.