Wistar Rats In Doses Research Articles

Acute Oral Toxicity Study of Povidone-Iodine in Wistar Rats Using Up-and-Down Procedure

This study was conducted to assess the acute oral toxicity of Povidone iodine in Wistar rats and determine its safety profile. The up and down method as per Organization for Economic Co-operation and Development guidelines using 15 adult male Wistar rats. They were randomly divided into three groups, given varying amounts of distilled water, 2000 and 5000 mg/kg to determine the median lethal dose (LD50). Clinical signs and mortality were observed for 48 hours and 14 days for immediate and delayed toxicity. Blood samples were collected at the end of the experiment for haematological and serum biochemical analysis for kidney and liver functions. Also, the kidney and liver were harvested, preserved, and processed for histomorphological evaluation. The result from this study indicates that Mortality (60 %) was observed in the group administered with 5000 mg/kg of PV-I within 3 h of administration. In contrast, the group served with 2000 mg/kg of PV-I, and the control remained viable up to 14 d of the experiment, the median lethal (LD50) dose of PV-I is less than 5000 mg/kg in Wistar rats. No significant (P> 0.05) difference was observed in the haematological parameters and serum biochemical markers for the kidney and liver function tests between the treatment and the control group. Furthermore, a histomorphological examination of the kidneys and liver shows normal kidneys with slight hepatic necrosis in the group administered with 2000 mg/ kg BW of PV-I. In conclusion, PV-I is safe for Wistar rats in doses below 2000 mg/kg.

Evaluation of Neuroprotective effect of Cassia occidentalis L. against Colchicine Induced Memory Impairment in Wistar Rats

Background: Alzheimer’s disease (AD) is a progressive neurological disorder that develops with aging. Objective: In this research, we have examined the anti - Alzheimer’s effect of ethanolic extract from roots of Cassia occidentalis L. on colchicine-induced Alzheimer’s in Wistar rats Methods: Ethanolic extract was obtained and spectroscopic, chromatography analysis was performed. Acute toxicity studies using Organization of Economic Co-operation and Development (OECD) Guidelines 423 were performed to examine and make sure that there were no signs of toxic effects. The induction of AD was done using colchicine which leads to symptoms like neurotoxicity, neuroinflammation, and neurodegeneration. In this experiment, a thorough analysis of body weight, behavioral parameters, locomotor activity, and biochemical evaluation was performed to estimate the medicinal properties of Cassia occidentalis L in treating Alzheimer’s disease. Results: Pharmacognostic analysis showed the presence of vascular bundles, starch grains, fibers, calcium oxalate crystals, elongated parenchyma, and collenchyma mucilage as shown in the supplementary files. Locomotor activity, Escape latency time, Conditioned avoidance response, and Transfer latency were improved with treatment. Interleukin- 6 (IL - 6) levels were reduced significantly in the Colchicine + 200 Cassia mg/kg group (739.2 ± 0.37 pg/ml) than in the Colchicine Group (850.6±0.40 pg/ml). Tumor necrosis factor (TNF-α) was decreased in the Colchicine + 200 Cassia mg/kg Group (1030.93±0.51 pg/ml) than in the Colchicine Group (1455.06±1.25 pg/ml). A significant decrease in total protein level was observed in the Colchicine Group (2.52±0.10 mg/ml), (3.33±0.90 mg/ml) as compared to Colchicine + 200 Cassia mg/kg Group (5.27±0.09 mg/ml, (5.01±0.10 mg/ml) respectively, in the Hippocampus and Entorhinal cortex. The levels of antioxidant enzymes such as Catalase (CAT), Serum superoxide dismutase (SOD), Reduced glutathione (GSH) and Malondialdehyde (MDA) were measured. When compared to the Colchicine Group (7.33±0.16 nM/ mg, the MDA level was lower in the Colchicine + 100 Cassia mg/kg Group (3.20±0.01 nM/ mg). The level of CAT in Colchicine + 200 Cassia mg/kg Group (7.01±0.03 μmoles of H2O2/mg of protein) was seen to be increased when compared to Colchicine Group (3.32 ± 0.17 μmoles of H2O2/mg of protein). The level of SOD in Colchicine + 200 Cassia mg/kg Group (7.43±0.02 U mg -1 of protein) was seen to be increased when compared with Colchicine Group (4.55±0.03 U mg -1 of protein). The level of GSH in Colchicine + 200 Cassia mg/kg Group (10.07±0.19 nM/mg -1 of protein) was increased when compared with the Colchicine Group (5.82±0.11nM/mg -1 of protein). Histopathology of the Hippocampus and Entorhinal cortex showed diminished amyloid plaques, and neurodegeneration in the treatment groups Conclusion: The present study showed that ethanolic extract from the roots of Cassia occidentalis L. At 100 and 200 mg/kg doses in Wistar rats improved memory damage, by reducing oxidative stress. Levels of the antioxidant enzymes as CAT, and SOD, GSH were increased and MDA was decreased. The cytokine levels in the serum of Wistar rats of IL-6 level and TNF-α level were reduced significantly. Estimation of total protein level was found to be increased. It restored neuronal degeneration in the Hippocampus, and Entorhinal cortex and reduced oxidative stress. This suggests that the ethanolic extract of Cassia occidentalis L. could be an effective therapeutic treatment for neurodegenerative diseases like AD.

Toxicological Characteristics of Bacterial Nanocellulose in an In Vivo Experiment-Part 1: The Systemic Effects.

This study aims to perform a toxicological and hygienic assessment of the safety of BNC in a subacute 8-week administration in rats. BNC was administered to male Wistar rats in doses of 0, 1.0, 10.0, and 100 mg/kg body weight for 8 weeks. Various parameters such as anxiety levels, cognitive function, organ masses, blood serum and liver biochemistry, oxidative stress markers, vitamin levels, antioxidant gene expression, and liver and kidney histology were evaluated. Low and medium doses of BNC increased anxiety levels and liver glutathione, while high doses led to elevated LDL cholesterol, creatinine, and uric acid levels. Liver tissue showed signs of degeneration at high doses. BNC did not significantly affect vitamin levels. The adverse effects of BNC are either not dose-dependent or fall within normal physiological ranges. Any effects on rats are likely due to micronutrient deficiencies or impacts on intestinal microbiota.

Effects of Acute and Repeated Dose Toxicity Profiling of Chelidonic Acid in Rats: in Silico and in Vivo Evidence.

Chelidonic acid is a phytoconstituent found in rhizomes of the perennial plant celandine. The current study aims to evaluate the acute and repeated dose oral toxicity study of chelidonic acid as per the OECD guidelines 425 and 407. The pharmacokinetic and toxicity profile of chelidonic acid was predicted using online servers and tools. A single dose of chelidonic acid (2000 mg/kg) was administered to female Wistar rats in an acute toxicity study, and the animals were monitored for 14 days. We studied the toxicity profile of chelidonic acid at 10, 20, and 40 mg/kg doses in Wistar rats for repeated dose toxicity (28 days). Clinical biochemistry, haematological, and urine parameters were estimated. A gross necropsy and histopathology were performed. A single oral dose of chelidonic acid (2000 mg/kg) showed no signs of toxicity or mortality. The Administration of chelidonic acid showed no significant alterations in haematological, biochemical, and urine parameters. The histopathology showed normal structure and architecture in all the vital organs. A gross necropsy of vital organs showed no signs of toxicity. The chelidonic acid was found to be safe at all selected dose levels in the acute and repeated dose toxicity study in rats.

Phytochemical profile, antioxidant activity, and acute toxicity of methanolic extracts of Annickia affinis (Exell) Versteegh & Sosef leaves stem bark and roots

This study aimed to determine the phytochemical profile, acute toxicity, and antioxidant activity of leaves, stem bark, and roots of methanolic extracts of Annickia affinis. Phytochemical screening was done to highlight the secondary metabolites present in the plant. The <em>in vitro</em> antioxidant activity was carried out using the DPPH free radical trapping method based on our extracts' reduction of the DPPH radical. This was evaluated by measuring the absorbance of all concentrations of extracts tested at 517 nm. Whereas the total phenol content was quantified using the reagent of “Folin-Ciocalteu,” measurable using a spectrophotometer at 765 nm.<strong> </strong>The in vivo acute toxicity study was conducted according to guideline 423 of the Organisation for Economic Co-operation and Development (OECD) protocol at a fixed dose in Wistar rats. Phytochemical screening of the different extracts revealed the presence of alkaloids, saponins, triterpenoids, anthraquinones, anthocyanins, and coumarins. The extracts of the leaves, stem bark, and roots showed good DPPH radical scavenging activity with IC<sub>50</sub> values of 0.34 µg/mL, 0.37 µg/mL, and 0.22 µg/mL, respectively; these values were very close to that recorded for the standard, Butyl hydroxytoluène (BHT) (0.14 µg/mL). The total phenolic contents were 122.11 <strong>µ</strong>gEqGA/g for the leaves, 47.11 <strong>µ</strong>gEqGA/g for the stem bark, and 109.95 <strong>µ</strong>gEqGA/g for the roots.<strong> </strong>An oral administration of all extracts did not cause an abnormal variation of the physiological parameters in female Wistar laboratory rats at doses of 2000 and 5000 mg/kg body weight up to 14 days after administration. The methanolic extracts of the leaves, stem bark, and roots of <em>A. affinis</em> are thus non-toxic at a dose as high as 5000 mg/kg body weight. They all have good antioxidant activity, the best activity recorded for the roots. It would be beneficial to suggest <em>A. affinis</em> to local populations against pathologies linked to oxidative stress after the preclinical and clinical tests.

Preclinical study of pharmacokinetic ADME processes of phenosanic acid <i>in vitro</i> and <i>in vivo</i>

BACKGROUND: Phenosanic acid is a synthetic antioxidant, the active ingredient of the original domestic drug recommended for the treatment of epilepsy. To improve the effectiveness and safety of the use of phenosanoic acid, additional study of its pharmacokinetic properties is necessary.
 AIM: To study the pharmacokinetic parameters of the active ingredient of the drug Dibufelon, capsule 200 mg (LLC Piq-Pharma, Russia) in vitro and in vivo systems in rats after single administration in one dose.
 MATERIALS AND METHODS: Phenosanic acid binding to blood plasma proteins, microsomal stability and permeability through the monolayer of Caco-2 cells were evaluated in in vitro tests. The pharmacokinetics parameters were studied after a single intragastric administration in Wistar rats in dose of 80 mg/kg. The samples were analyzed by HPLC-UV.
 RESULTS: A high variability in the degree of binding of phenosanic acid to blood plasma proteins by 2065% depending on the concentration was revealed, relatively high microsomal stability (half-life 1106 789 min, internal clearance 2.05 0.86 l/min/mg protein of liver microsome; residual content after 60 min incubation 87.9 7.8%) and the ability to penetrate through the monolayer of cells Caco-2. The rapid absorbtion of the substance into the systemic bloodstream was established its maximum concentration in blood plasma was observed already 3.6 1.2 hours after administration, and its slow removal from the systemic bloodstream the half-life was about 19 h, the average retention time was about 29 h. Phenosanic acid with different degrees of intensity was distributed to all the examined organs and tissues: kidneys liver brain omentum muscle, and invariably excreted in a small amount with urine and feces, about 0.04% and 5.5%, respectively.
 CONCLUSIONS: As a result of the study, it was found that phenosanic acid is characterized by rapid absorbtion into the systemic bloodstream and a long stay in it invariably, which may be due to the peculiarities of its binding to blood plasma proteins and relatively high metabolic stability, revealed during the corresponding in vitro tests. The study of the permeability and transport of phenosanic acid showed that it can presumably be attributed to compounds with medium permeability and is not a substrate for the transport protein P-glycoprotein (P-gp). The study of tissue availability of phenosanic acid confirmed its entry into peripheral tissues, including the brain, which is the area of implementation of the anticonvulsant effect.

Acute Oral Toxicity Study of Indigofera Tinctoria L. Aqueous Extract, a Substitute for Synthetic Food Colorants: Fourier Transform Infrared Spectroscopy, Biochemical, and Histopathological Investigation

Background and Purpose: This research aimed to investigate the in vivo acute oral toxicity of aqueous extract of Indigofera tinctoria L. in different doses in Wistar rats. Materials and Methods: Twenty-five male rats were divided into five groups (n=5 for each group). Group I served as the control, and the other four groups received I. tinctoria (100, 250, 500, and 1000mg/kg body weight) for 14 days. At the end of the experiment, all animals were killed, and the blood samples were collected for biochemical assay. The fourier transform infrared spectroscopy (FTIR), and histopathological analyses were done on different tissues. Results: According to the results, rats who received I. tinctoria (100mg) had lower triglyceride than the control group. Moreover, I. tinctoria administration in all groups did not change the serum glucose, creatinine, urea, and high-density lipoprotein amounts. In addition, using 100mg of the extract resulted in a lower alanine transaminase level than the control. Also, histopathology data indicated no signs of tissue toxicity and degeneration in all experimental groups. Furthermore, FTIR indicated that I. tinctoria had not changed the tissues’ protein structure. Conclusion: It can be concluded that I. tinctoria can be used as colorant food up to 1000mg/kg body weight.

Brain response to intraperitoneal and oral administration of monosodium glutamate in wistar rats

Background: It has been reported that at high concentration monosodium glutamate (MSG) administration induces neurological toxicity caused by increased concentration of glutamate that promotes the production of free radicals and apoptosis. The blood–brain barrier is used by the brain to protect itself against the effect of glutamate and other neurotoxins but its level of protection varies with age. Aim and Objective: In this present study, we examined brain responses to combined intraperitoneal and oral administration of MSG at different doses in Wistar rats. Material and Method: 4 mg/g MSG was administered intraperitoneally to neonates in postnatal days 2, 4, 6, 8, and 10–2 groups and one of the groups was further administered 10 mg/g MSG orally as adult, while the last group received 10 mg/g MSG as adults only for 21 days. At the end of the 21 days, brain tissue was collected and used to determine MSG effect. Results: In the brain tissue, MSG administration caused a significant increase (P

Antihyperglycaemic activity of ethylacetate extract of Chlorophytum alismifolium in type 2 diabetes: The involvement of peroxisome proliferator-activated receptor-γ and dipeptidyl peptidase-4

ObjectiveThis research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium (EACA) tubers in a type 2 diabetes model. MethodsThe tubers were processed and sequentially extracted in hexane followed by ethylacetate, using a Soxhlet apparatus, and subjected to gas chromatography-mass spectrometry (GC–MS). The acute toxicity of EACA was investigated in albino Wistar rats. An antihyperglycaemic study was carried out using high-fat diet (pelletized diet and margarine in the ratio of 10:1 and 20% fructose solution) and streptozotocin-induced hyperglycaemic Wistar rats. The effects of the extract (150, 300 and 600 mg/kg) on blood glucose level, insulin, peroxisome proliferator-activated receptor-γ (PPAR-γ) and dipeptidyl peptidase-4 (DPP-4) were evaluated using enzyme-linked immunosorbent assay. ResultsThe oral median lethal dose in Wistar rats was estimated to be > 5000 mg/kg. Treatment with EACA at all doses significantly reduced the fasting blood glucose levels, compared to the hyperglycaemic control, and over time. Administration of EACA increased the serum insulin and PPAR-γ levels while decreasing DPP-4 levels. GC–MS analysis revealed the presence of 13 compounds, with isothiazole and isoxazolidine covering total area of 24.6% and 22.69%, respectively. ConclusionThe findings from this study showed that EACA has important compounds with beneficial effect in type 2 diabetes and acts by increasing insulin secretion and PPAR-γ level and decreasing DPP-4 activity.

Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury.

The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC–ESI-Q-TOF–MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.

Anti-hyperglycemic and genotoxic studies of 1-O-methyl chrysophanol, a new anthraquinone isolated from Amycolatopsis thermoflava strain SFMA-103

The compound 1-O-methyl chrysophanol (OMC) which belongs to a class of hydroxyanthraquinones was isolated from Amycolatopsis thermoflava strain SFMA-103 and studied for their anti-diabetic properties. OMC was evaluated as an anti-diabetic agent based on in silico studies which initially predicted the binding energy with α-amylase (−188.81 KJ mol−1) and with α-glucosidase (70.53 KJ mol−1). Further, these results were validated based on enzyme inhibition assays where OMC demonstrated enzyme inhibitory activity towards α-amylase (IC50 3.4 mg mL−1) and α-glucosidase (IC50 38.49 μg mL−1). To confirm the anti-diabetic activity, in vivo studies (oral dose in Wistar rats) revealed that OMC inhibited significantly the increase in glucose concentration at 100 mg/kg as compared to starch control (p < 0.05). Further, to understand the safety of OMC as a therapeutic agent, the genotoxic analysis was performed in both in vitro Chinese Hamster Ovary cells (250, 500, and 1000 µM/mL) and in vivo Swiss albino mice (250, 500, and 1000 mg/kg). In vitro results showed that OMC concentration of up to 250 µM/mL did not elicit significant changes in CAs, MI, and MN counts in CHO cells. Similarly, in mice experiments (i.p. injection), no significant changes in CAs, MI, and MN induction were observed till 500 mg/kg of OMC when compared with chrysophanic acid (Cy) (200 mg/kg). In addition, mice that received the lowest dose of OMC (250 mg/kg) did not show any histological changes in liver, kidney, and heart. The study concluded that five times higher therapeutic dose (100 mg/kg) of OMC can be utilized against hyperglycemia with no genotoxic effects.

Dose comparative evaluation of analgesic activity of simvastatin in wistar rats

Background: Pain is defined as an unpleasant sensation and emotional experience associated with or without tissue damage. Analgesics are the drugs that relieve pain. Statins are mainly employed in the treatment of hyperlipidaemias. Simvastatin belongs to HMG-CoA reductase inhibitors, which is the rate limiting step in the cholesterol synthesis. Analgesic effect of Simvastatin is a pleotropic effect, but the exact mechanism is not known. During our literature search we came across limited number of studies that evaluated the analgesic activity of simvastatin at different doses; however, the results were controversial at lower doses. Hence this study was under taken to evaluate analgesic activity Simvastatin at different doses in Wistar rats and also to compare its analgesic activity with Tramadol. Aims and Objectives: (i) To evaluate analgesic activity Simvastatin at different doses in Wistar rats; (ii) To compare the analgesic activity of Simvastatin with Tramadol. Materials and Methods: Analgesic activity of simvastatin was evaluated wistar rats using Tail Flick Model and Eddy’s Hot Plate Model. Normal saline with Polyethylene glycol (2 ml/kg), Tramadol (10 mg/kg), Simvastatin (5 mg/kg, 10 mg/kg and 30 mg/kg) dissolved in Polyethylene glycol, were given orally to the randomly divided 5 groups of 6 animals each. Maximum possible analgesia was calculated at 30, 60 and 90 min in both the models and compared between the 5 groups. Observations were analysed using ANOVA and post hoc Tukey’s test. Results: Simvastatin at doses 5 mg/kg and 10 mg/kg body weight produced significant Maximal possible analgesia at 30 and 60 min in both the models (

Alterations of Antioxidant Status and Mitochondrial Succinate Dehydrogenase Activity in the Liver of Wistar Strain Albino Rats Treated with by Ethanol Extracts of Annona senegalensis Pers (Annonaceae) Stem Bark

Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub- acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The LD50 value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.

Influence of ACTG4-7-PGP (Semax) on Morphofunctional State of Hepatocytes in Chronic Emotional and Painful Stress.

We studied the effect of intraperitoneal administration of peptide ACTG4-7-PGP to male Wistar rats in doses of 5, 50, 150, and 450 μg/kg on the morphofunctional state of hepatocytes in chronic emotional and painful stress. A dose-dependent stress-limiting effect of the peptide was observed: it normalized the protein synthesis function of the liver and serum activity of ALT. The anticytolytic effect of the peptide increased with increasing its dose against the background of the increase in the relative number of multinucleated and multinucleolated cells and deceleration of the recovery of serum protein concentration. The decrease of hepatocyte cytolysis against the background of more intense morphological signs of protein synthesis processes attests to activation of reparative processes in the liver parenchyma via enhanced constitutional synthesis of protein.

Effects of controlled doses of Oxyelite Pro on physical performance in rats.

BackgroundOxyElite Pro (OEP) is a dietary supplement to increase metabolism which contains as key stimulant the ingredient 1,3-dimethylamylamine (DMAA). Serious adverse effects have been reported after OEP consumption however, these effects are related to poisoning or overdose. To our knowledge, no one studied the effects of OEP at controlled doses. Thus, the aim of this study was to evaluate acute and chronic OEP affects, at controlled doses in Wistar rats, on physical performance, metabolic parameters, liver injury markers and oxidative stress markers and mitochondrial biogenesis in skeletal muscle.MethodsRats were divided in control, 4.3 mg OEP/kg, 12.9 mg OEP/kg and 25.8 mg OEP/kg. All groups were submitted to supplementation with OEP for 4 weeks and the experimental protocols were performed 30 min after the first OEP administration (acute response) and 30 min after the last OEP administration at the end of the forth week (chronic response).ResultsRunning distance and running time increased after acute administration of 12.9 mg OEP/kg (2.6-fold) and 25.8 mg OEP/kg (2.8-fold). Since no effect on the exercise tolerance test was observed at the lower OEP dose (4.3 mg OEP/kg), this group was removed from further analyzes. On other hand, running distance and running time decreased after daily supplementation for 4 weeks also in both groups (64% in 12.9 mg OEP/kg and 72% in 25.8 mg OEP/kg). Chronic supplementation at both 12.9 and 25.8 mg OEP/kg decreased TBARS levels in soleus muscle (36 and 31%) and liver (43 and 25%). AOPP was also decreased by both doses in the liver (39 and 45%). Chronic administration of the highest dose, 25.8 mg OEP/kg, was able to reduce mRNA expression of PGC-1α in soleus muscle (25%). No effect was found in other analyses such as spontaneous physical activity, body weight, food and water intake, hepatic toxicity, cardiac oxidative stress and mitochondrial DNA amount.ConclusionMaximum and not recommended doses of OEP ingested acutely presented stimulating effect on the ability to exercise. However, its daily consumption for 4 weeks showed antioxidant effects in soleus muscle and liver which may have decreased the PGC-1α mRNA expression on soleus muscle and contributed to the impaired performance in the exercise tolerance test.

Influence of orally introduced silver nanoparticles on content of essential and toxic trace elements in organism

Nanoscale colloidal silver (NCS) is one of the most popular products of nanotechnology and is widely used in cosmetics, food supplements, and other types of consumer products. The aim of this work is to study the influence of NCSs orally introduced into rats during an experiment lasting 92 days on some indicators of homeostasis of essential and toxic trace elements. The Argovit-C NCSs produced by Vector Vita LTD, Novosibirsk, Russia with silver (Ag) nanoparticles of the diameter in the range of 5-80 nm according to transmission electron microscopy and dynamic laser light scattering. The drug is introduced into growing male Wistar rats in doses ranging from 0.1 to 10 mg/kg body weight (b.w.) for 1 month by gavage and then with a diet consumed for 62 days. The control animals receive deionized water or an aqueous solution of the stabilizer polyvinylpyrrolidone. The content of Ag, cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) in the liver, kidneys, and spleen is determined by mass spectrometry with inductively coupled plasma; selenium (Se) in serum and urine is measured by spectrofluorimetric method and glutathione peroxidase activity by the enzymatic spectrophotometric method. The dose-dependent accumulation of Ag in the animal liver at a dosage ranging 0.1–10 mg/kg b.w. and kidney and spleen in the range of 0.1–1 mg/kg b.w. is revealed. A significant decrease in the content of Cu in the kidneys; a decrease in Zn and Co content and increase in Mn content in the liver; and an increase in Cd, Cr, and Ni in spleen of animals receiving NCS at various doses are found. A significant positive correlation is found between the levels of Ag and Cd, Ni, Cr in the spleen, and a negative one is found between Ag and Cu in the kidneys. Indicators of Se provision (urinary excretion, the content in the blood plasma, the activity of glutathione peroxidase) are significantly lower in rats receiving NCS at a dose of 1.0–10 mg/kg b.w. Thus, NCSs, entering the body through the gastrointestinal tract at a dose of silver of at least 1 mg/kg b.w. may affect the homeostasis of essential and toxic trace elements. The antagonism of Ag (as part of the NCS) and Se in the composition of the diet should be taken into account in assessing the safety of widely used food supplements–sources of colloidal Ag.

Effect of cadmium chloride exposure during the induction of collagen induced arthritis

The precise cause of autoimmune diseases such as rheumatoid arthritis remains uncertain. Collagen induced arthritis (CIA) in animals is the most commonly used model of human rheumatoid arthritis (RA). Exposure of humans and animals to toxic metals is widespread. Cadmium is one of the most prevalent nephrotoxic heavy metal, but it may cause other systemic toxicity as well. Cadmium may cause adverse health effects by impairment of the immune systems and induction of reactive oxygen species. Since rheumatoid arthritis pathogenesis involve immune system disorder and chronic inflammation, the present study has been designed to find out the effect of cadmium chloride exposure on clinical manifestation of development of collagen induced rheumatoid arthritis. Arthritis was induced in rats by intradermal injection of emulsion of type II collagen in Complete Freund’s Adjuvant. Rats were treated with cadmium chloride dissolved in drinking water at concentrations of 5ppm and 50ppm for 21days from day of immunization. The effects of cadmium in the rats were assessed by biochemical parameters (articular elastase, articular nitrite, lipid peroxidation, reduced glutathione, catalase and superoxide dismutase) histopathological analysis and immunohistochemical expression of pro-inflammatory cytokines in rat joint tissue. Histopathological changes further confirmed the biochemical and immunohistochemical results. Our results suggest that exposure to cadmium chloride during the induction phase of collagen induced arthritis abrogate disease development at lower dose whereas exacerbates at higher dose in Wistar rats.

Reduction of Locomotor and Brain Activity of Wistar Rats after Serial Administration of Titanium Dioxide

Nanoparticles of titanium dioxide (TiO2) are widely used nanomaterial with particle size below 100 nanometers TiO2 is applied as a pigment to provide whiteness to such products as paints, paper, foodstuffs, medicines, toothpastes, etc. However, neurotropic properties of titanium dioxide remains unclear. This work aimed evaluation of neurotoxic effects of titanium dioxide nanoparticles (12 nm particle size) serially administered to Wistar rats in dose of 250 mg/kg for 7 days. Behavioral and physiological observations were registered immediately after treatment. Results showed that nanoTiO2 particles caused reducing of general motor activity in rats and a shift of the electroencephalogram (EEG) power toward low frequencies of (EEG), while aggressive behavior, and open field behavior did not change. The depressive effect of titanium dioxide nanoparticles on the central nervous system (CNS) observed in our study might be related to neuronal damage caused by an increase in reactive oxygen species (ROS) as well as the impairment of synaptic transmission.

Antinociceptive and Anti-edematous Activities of the Essential Oils of Two Balkan EndemicLaserpitium Species

In this paper antinociceptive and anti-edematous effects are examined of the essential oils of the underground parts of two Balkan endemic Laserpitium species (Apiaceae), L. zernyi and L. ochridanum. Furthermore, the essential oil of the underground parts of L. ochridanum is chemically characterised by GC and GC-MS. Antinociceptive and anti-edematous effects were measured in a rat model of localized inflammation, induced by carrageenan, using apparatus for the modified paw-pressure test, and plethysmometer, respectively. The effects of both Laserpitium essential oils were measured after oral gavage administration to male Wistar rats in doses of 25, 50 and 100 mg/kg. The main constituents of L. ochridanum essential oil were: alpha-pinene (33.2%), alpha-bisabolol (10.3%) and chamazulene (14.9%). The essential oil of L. zernyi was previously shown to be rich in alpha-pinene (31.6%) and alpha-bisabolol (30.9%). Both examined essential oils produced a significant dose-dependent antinociceptive effect. The corresponding ED50 +/- SEM in producing antinociception were 45.9 +/- 4.9 mg/kg and 42.4 +/- 2.1 mg/kg for L. zernyi and L. ochridanum oil, respectively. Both essential oils also significantly reduced paw edema in a dose-dependent manner. The estimated ED50 +/- SEM values for the anti-edematous effect were 36.3 +/- 4.5 mg/kg for L. zernyi oil and 45.1 +/- 11.3 mg/kg for L. ochridanum oil. These results suggest that the essential oils of both investigated Laserpitium species may be effective against pain and edema present in various inflammatory conditions.

Acute oral toxicity and histopathological study of combination of endosulfan and cypermethrin in wistar rats

Background:Endosulfan, a neurotoxic organochlorine insecticide and cypermethrin, a synthetic pyrethroid insecticide used to control pests in domestic, industrial, and agricultural situations.Materials and Methods:The present study was carried out to investigate the acute oral toxicity, behavioral and histopathological changes of combination of endosulfan and cypermethrin in albino rats. According to Miller and Tainter analysis method, at 48 h, LD50 value of combination of endosulfan and cypermethrin (ratio 1:1) in rats was found to be 691.83 mg/kg bw by oral gavage.Results:When combination of both these pesticides was administered orally at concentration of 103.72 mg/kg bw, 172.95 mg/kg bw and 207.50 mg/kg bw, respectively, as a single dose, no significant changes in behavior of rats was observed, neither in dosed nor in control group of rats. Combination of endosulfan- and cypermethrin-treated rats showed mild histopathological changes in liver and kidney in group IV (207.50 mg/kg BW) as compared to the control. However, no significant changes were observed in brain and small intestine at either dose of combination of endosulfan and cypermethrin with respect to control.Conclusion:Thus, the present study, first of its kind in India, demonstrated the oral toxicity, behavioral, and histo-architectual alterations after induction of combination of endosulfan and cypermethrin at acute doses in Wistar rats.