Oxidative stress and inflammatory responses of rat following acute inhalation exposure to iron oxide nanoparticles.

In this research, we investigated the toxicity responses of rat following a continuous 4 h inhalation exposure of only the head and nose to iron oxide nanoparticles (Fe(3)O(4) NPs, size = 15-20 nm). The rats for the investigation were exposed to a concentration of 640 mg/m(3) Fe(3)O(4) NPs. Markers of lung injury and proinflammatory cytokines (interleukin-1ß, tumor necrosis factor-α, and interleukin-6) in bronchoalveolar lavage fluid (BALF) and blood, oxidative stress in lungs, and histopathology were assessed on 24 h, 48 h, and 14 days of postexposure periods. Our results showed a significant decrease in the cell viability, with the increase in the levels of lactate dehydrogenase, total protein, and alkaline phosphatase in the BALF. Total leukocyte count and the percentage of neutrophils in BALF increased within 24 h of postexposure. Immediately following acute exposure, rats showed increased inflammation with significantly higher levels of lavage and blood proinflammatory cytokines and were consistent throughout the observation period. Fe(3)O(4) NPs exposure markedly increased malondialdehyde concentration, while intracellular reduced glutathione and antioxidant enzyme activities were significantly decreased in lung tissue within 24-h postexposure period. On histological observation, the lung showed an early activation of pulmonary clearance and a size-dependant biphasic nature of the Fe(3)O(4) NPs in causing the structural alteration. Collectively, our data illustrate that Fe(3)O(4) NPs inhalation exposure may induce cytotoxicity via oxidative stress and lead to biphasic inflammatory responses in Wistar rat.

Repeated dose dermal toxicity study of nano zinc oxide with Sprague-Dawley rats.

CONTEXT: In light of the increased use of zinc oxide nanoparticles in cosumer products such as sunscreens, there is a need for screening the potential dermal toxicity of these nanoparticles. OBJECTIVE: The aim of this study is to identify the risk associated with the nano zinc oxide at realistic exposure levels through dermal route. This study is to understand the toxic potential of nano zinc oxide through repeated dermal exposure for a period of 28 days. MATERIALS AND METHODS: Six- to 8-week-old Sprague-Dawley rats were applied with three different doses (75, 180, and 360 mg/kg body weight) of nano zinc oxide (20 nm) at 5 days/week basis for a period of 28 days. The dose levels were calculated taking into consideration the percentage of nanomaterial in the sunscreen, number of application times, and average weight of the consumer in order to assess the realistic risk related to it. Control group animals were applied with distilled water alone. The collagen content was estimated in skin and tail of all the treated and control animals. RESULTS: The content was significantly decreased in all the nano zinc oxide-treated groups with an inverse dose relationship. DISCUSSION AND CONCLUSION: The percentage collagen loss was high in skin when compared with tail. This may be due to the site of application where in the nano zinc oxide may be passed through skin due to their small size and may induce oxidative stress. Hence, we suggest that regulators and industry need to address the toxicity of nanomaterials with a realistic exposure assessment rather following conventional dose measurements following existing protocols.

Nanoemulsified ethanolic extract of Pyllanthus amarus Schum & Thonn ameliorates CCl4 induced hepatotoxicity in Wistar rats.

Phyllanthus amarus (PA) is commonly used in traditional medicine for hepatoprotectivity. The major limitation is that, treatment requires a large quantity of herbal extract for a longer duration. Aim of the present study was to encapsulate ethanolic plant extract for sustained release of constituents in intestine and facilitate maximum absorption. The efficacy was compared for the hepatoprotective activity of nanoencapsulated ethanolic extract of P. amarus (NPA) and PA in carbon tetrachloride (CCl4) induced hepatotoxic male rats. Based on total phenol content (TPC), the loading efficiency of nanocapsules was 89% (pH 7.0) and optimum concentration was 2:18 (mg/mL) for plant extract: olive oil. Scanning electron microscopy (SEM) showed a spherical morphology, photon correlation spectroscopy (PCS) identified mean particle diameter as 213 nm and Fourier transform infrared spectroscopy (FT-IR) revealed that the phytoconstituents were stable. An oral dose of NPA (20 mg/kg body wt.) showed a better hepatoprotective activity than PA (100 mg/kg body wt.) and also repeated dose oral toxicity proved to be safe. These biochemical assessments were supported by rat biopsy examinations. In conclusion, the nanoemulsification method may be applied for poor water-soluble ethanolic herbal extracts to reduce the dosage and time.

Toxicity Assessment of Expired Pesticides to Green Algae Pseudokirchneriella subcapitata.

In order to investigate the effect of expired pesticides on the yield and growth rate of green algae Pseudokirchneriella subcapitata, a study was conducted as per the Organisation for Economic Cooperation and Development (OECD) guideline number 201. Fifteen expired pesticide formulations, most commonly used in Indian agriculture, were tested in comparison with their unexpired counterparts. The expired pesticide formulations studied belonged to various class and functional groups: organophosphate, pyrethroid-based insecticides; azole-based fungicides; acetamide, propionate, acetic acid-based herbicides; fungicides mixtures containing two actives-azole and dithiocarbamate. The toxicity endpoints of yield (EyC50: 0-72 h) and growth rate (ErC50: 0-72 h) of Pseudokirchneriella subcapitata for each pesticide formulation (both expired and unexpired pesticides) were determined statistically using TOXSTAT 3.5 version software. The results pointed out that some expired pesticide formulations exhibited higher toxicity to tested algal species, as compared to the corresponding unexpired pesticides. These data thus stress the need for greater care to dispose expired pesticides to water bodies, to avoid the effects on aquatic ecospecies tested.

Sub acute toxicity assessment of glipizide engineered polymeric nanoparticles.

To our knowledge, no such polymeric nanoparticle formulation toxicity study has been reported for oral use. The oral route of drug administration is generally preferred because of its versatility, safety and relative patient comfort. Hence, there is an outstanding need of research for polymeric nanoparticles to find whether they are stable for prolonged shelf life, and yet have no toxicity when administered orally. The main objective of this study is to assess the safety of Glipizide (GZ) loaded polymeric nanoparticle systematically and to observe the toxic effects of nanoparticles on the functions of various tissues and organs in rats. The rats were randomly divided into 7 groups (6 in each group); viz. one normal control group (received saline), two groups (1:2 and 1:5 ratio of GZ-Chitosan nanoparticle), two groups (1:2 and 1:5 ratio of GZ-Poly(methyl methacrylate) nanoparticle) and two groups (1:2 and 1:5 ratio of GZ-Ethyl Cellulose nanoparticle). After 30 days of nanoparticle administration, the blood haematology and biochemistry were investigated, along with the histopathological examination. The rats did not show any significant changes in all the parameters studied and the results clearly evidenced its safety. All formulations showed in vitro haemolytic activity less than 5%. Conclusion drawn from the present study is that the polymeric nanoparticles may be a suitable device for safe oral administration. A rigorous safety of these nanoparticles would enable their use in the field of diabetic therapy.

Acute inhalation toxicity of cerium oxide nanoparticles in rats.

The aim of the present study was to assess the acute toxic potential of cerium oxide nanoparticles (CeO(2) NPs) in rats when exposed through the head and nose inhalation route. The rats were exposed to CeO(2) NPs and the resultant effects if any, to cause cytotoxicity, oxidative stress and inflammation in the lungs were evaluated on a 24h, 48h and 14 day post exposure period. Our results showed a significant decrease in the cell viability, with the increase of lactate dehydogenase, total protein and alkaline phosphatase levels in the bronchoalveolar lavage fluid (BALF) of the exposed rats. Total leukocyte count and the percentage of neutrophils in BALF were elevated within 24h of post exposure. The concentrations of pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) were significantly increased in the BALF and in the blood throughout the observation period. The level of malondialdehyde was elevated with the decreased levels of intracellular reduced glutathione (GSH) in the lung after exposure. The alveolar macrophages (AMs) and neutrophils overloaded with phagocytosed CeO(2) NPs were observed along with non-phagocytosed free CeO(2) NPs that were deposited over the epithelial surfaces of the bronchi, bronchiole and alveolar regions of lungs within 24h of post exposure and were consistent throughout the observation period. A well distributed, multifocal pulmonary microgranulomas due to impairment of clearance mechanism leading to biopersistence of CeO(2) NPs for an extended period of time were observed at the end of the 14 day post exposure period. These results suggest that acute exposure of CeO(2) NPs through inhalation route may induce cytotoxicity via oxidative stress and may lead to a chronic inflammatory response.

In vitro characterization and invivo toxicity study of repaglinide loaded poly (methyl methacrylate) nanoparticles.

With the objective to achieve prolonged drug release, especially for the treatment of diabetes mellitus, and thereby to reduce the side effects of administration of conventional dosage form, repaglinide loaded PMMA nanoparticles have been formulated. These nanoparticles have been developed by solvent evaporation method and were subjected to various studies for characterization including photon correlation spectroscopy (PCS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). These studies favorably revealed that the mean particle diameter of optimized formulation was 108.3nm and had spherical morphology with amorphous nature. Moreover, these particles were also subjected to Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) for compatibility analysis between drug and polymer. The results were positive and showed that, there were no interaction between drug and polymer. The optimized formulation demonstrated favorable in vitro prolonged release characteristics. Experimental in vitro release data were substituted with available mathematical models to establish the mechanism of release of repaglinide and was found to follow zero order, diffusion and erosion mechanisms. The in vivo toxicity study in albino rats showed no significant change in biochemical and pathological examinations. Hence, the designed system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance of repaglinide.

Poly(D,L-lactic-co-glycolic acid) nanoencapsulation reduces Erlotinib-induced subacute toxicity in rat.

Erlotinib-HCl is a quinazoline derivative used as a drug in the therapy of non-small-cell lung cancer. The present study was conducted to compare the subacute toxicity induced by Erlotinib-HCl delivered to rats as nanoparticles and as free drug. Wistar rats were orally administered with a daily dosage of 200 mg kg(-1) Erlotinib-HCl either as free drug or as Poly(D,L-lactic-co-glycolic acid) (PLGA) encapsulated nanoparticles. After four weeks of treatment, the animals were analyzed for toxicological changes. Although nanoparticulate form of the drug did not induce any toxicity, free drug significantly reduced the levels of white blood cells (WBC), red blood cells (RBC) and haemoglobin, while increasing the levels of neutrophils and corpuscular haemoglobin. Moreover, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly increased in the animals administered with free drug. Histopathological studies confirmed significant damage to the internal organs of animals treated with free drug. Whereas, the internal organs of animals treated with the drug encapsulated in PLGA nanoparticles were more or less similar to the healthy organs. Our results show that Erlotinib-HCl delivered in the form of nanoparticles has less toxic effect than the free drug in experimental rats.