RESUMEN
Titanium dioxide (TiO2) nanoparticles (NPs) are produced abundantly and are frequently used as a white pigment in the manufacture of paints, foods, paper, and toothpaste. Despite the wide ranges of uses, there is a lack of information on the impact of NPs on animal and human health. In the present study, rats were exposed to different doses of TiO2 nanoparticles and sacrificed, respectively, 4 days, 1 month, and 2 months after treatment. Dosage of TiO2 in tissues was performed by ICP-AES and revealed an important accumulation of TiO2 in the liver. The nanoparticles induced morphological and physiological alterations in liver and kidney. In the liver, these alterations mainly affect the hepatocytes located around the centrilobular veins. These cells were the site of an oxidative stress evidenced by immunocytochemical detection of 4-hydroxynonenal (4-HNE). Kupffer cells are also the site of an important oxidative stress following the massive internalization of TiO2 nanoparticles. Enzymatic markers of liver and kidney functions (such as AST and uric acid) are also disrupted only in animals exposed to highest doses. The metabonomic approach allowed us to detect modifications in urine samples already detectable after 4 days in animals treated at the lowest dose. This metabonomic pattern testifies an oxidative stress as well as renal and hepatic alterations.
RESUMEN
Nowadays, nanoparticles (NPs) of titanium dioxide (TiO2) are abundantly produced. TiO2 NPs are present in various food products, in paints, cosmetics, sunscreens and toothpastes. However, the toxicity of TiO2 NPs on the central nervous system has been poorly investigated until now. The aim of this study was to evaluate the toxicity of TiO2 NPs on the central nervous system in vitro and in vivo. In cell cultures derived from embryonic cortical brain of rats, a significant decrease in neuroblasts was observed after 24 to 96 h of incubation with TiO2 NPs (5 to 20 µg/ml). This phenomenon resulted from an inhibition of neuroblast proliferation and a concomitant increase in apoptosis. In the same time, a gliosis, characterized by an increase in proliferation of astrocytes and the hypertrophy of microglial cells, occurred. The phagocytosis of TiO2 NPs by microgliocytes was also observed. In vivo, after intraperitoneal injection, the TiO2 NPs reached the brain through the blood brain barrier and the nanoparticles promoted various histological injuries such as cellular lysis, neuronal apoptosis, and inflammation. A reduction of astrocyte population was observed in some brain area such as plexiform zone, cerebellum and subependymal area. An oxidative stress was also detected by immunohistochemistry in neurons of hippocampus, cerebellum and in subependymal area. In conclusion, our study demonstrated clearly the toxic impact of TiO2 NPs on rat brain and neuronal cells and pointed about not yet referenced toxicity impacts of TiO2 such as the reduction of neuroblast proliferation both in vitro and in vivo.
RESUMEN
AIMS: We used a rat model of renal ischemia (35 min) to test the potential involvement of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in the process of S3 tubule regeneration. METHODS: A monoclonal antibody specific for murine PECAM-1 was injected i.p. immediately after kidney reperfusion or 48 h post-ischemia. One day before ischemia, each animal received an i.p. injection of 80 mg/kg 5-bromo-2'-deoxyuridine (BrdU). Experimental animals were sacrificed 1, 2, 3, 7 and 14 days post-ischemia. Renal sections were processed to characterize the histopathological alterations and the distribution of BrdU-immunopositive cells. RESULTS: Our observations showed that anti-PECAM-1 administration was associated with an inhibition of S3 tubule regeneration along with a progressive cystic dilatation of renal tubules that was particularly prominent 2 weeks post-ischemia. Interestingly, injection of anti-PECAM-1 48 h post-ischemia failed to block renal regeneration and was followed by a normal re-epithelialization of S3 tubules. CONCLUSION: Our data showed that the blockade of PECAM-1 immediately after kidney reperfusion inhibits tubular regeneration. These observations suggest that transendothelial migration of extrarenal cells could be a precocious and pivotal step in kidney reparation, but also suggest that these extrarenal cells could be essential to the process of tubular regeneration.
