Different Tissues Of Rat Research Articles

The effects of some antibiotics from cephalosporin groups on the acetylcholinesterase and butyrylcholinesterase enzymes activities in different tissues of rats

In our study, it was aimed to investigate the effects of cefazolin, cefuroxime, and cefoperazon injected to rats on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activities in the heart, brain, eye, liver, and kidney tissues of rats. Liver AChE activity at the 1st and 3rd hours of cefuroxime groups was higher than the control group at the same time (p <.05). The AChE activity of the heart tissue decreased in the cefazolin group compared to the control group at the same hour, whereas it increased in the cefuroxime group (p <.05). AChE activities of kidney tissue of cefazolin and cefuroxime groups were lower than those of the same control group on the 3rd and started to increase on the next hours (p <.05). BChE activity is measured in tissues increased within the first three hours and decreased significantly within the first hour in the cefoperazone group (p <.05).

The Quantum-Mechanical Sensitivity of Cell Hydration in Mammals

The elucidation of the mechanism on the biological effects of weak chemical and physical factors on cells and organism is one of the modern problems in life sciences. According to the Receptor Theory of Prof. Bernard Katz the impact of the biological substances on cells is realized through the activation of ligand-gated ion channels in the membrane. However, this theory doesn’t provide a satisfactory explanation on the similar biological effects of extremely low concentrations of different chemical substances, which are unable to activate the ionic channels in the membrane and have non-linear dose-dependent effect on cells. Previously we have suggested that the metabolic control of cell hydration serves as a universal quantum-mechanical sensor for different weak physical and chemical signals. For supporting this hypothesis, in this article the comparative study of the effects of low concentrations of both cold (non-radioactive) and [3H]-ouabain (specific inhibitor for Na+/K+-ATPase) on the hydration in different tissues of rats has been performed. The obtained data have shown that cold and [3H]-ouabain have different effects on cell hydration and such a difference depends on the initial metabolic state of tissues. On the basis of our previous and present results it is suggested that such a quantum-mechanical sensitivity of cell hydration is realized through the cyclic-nucleotides-dependent Na+/Ca2+ exchange, having a crucial role in the metabolic regulation of cell hydration.

Impact of selenium status on Aroclor 1254-induced DNA damage in sperm and different tissues of rats

Aroclor 1254 is a commercial mixture of polychlorinated biphenyls (PCBs), which are widespread environmental pollutants. It is used as non-flammable heat transfer agent and plasticizer. Animal studies have reported that Aroclor 1254 exerted toxic effects in different organs and systems. Although the evidences are limited, it seems reasonable that Aroclor 1254 may have a potential for similar adverse effects in humans. Selenium (Se) is a trace element and an important component of cellular antioxidant defense. This study was designed to investigate the effects of different Se status on the genotoxicity of Aroclor 1254 in sperm and different organs of Sprague-Dawley rats using Comet assay. Se deficiency (SeD) was generated by feeding 3-week old Sprague-Dawley rats with <0.05 Se mg/kg diet for 5 weeks. Se supplementation groups (SeS) were fed with 1 mg Se/kg diet. Aroclor 1254-treated rats received 10 mg/kg dose by gavage during the last 15 d of feeding period. SeD increased DNA damage in all of the organs as well as in lymphocytes and sperm. Aroclor 1254 treatment caused pronounced changes in liver, kidney and brain cells along with marked increases in lymphocytes and sperm. Se supplementation provided full or partial protection decreases in Aroclor 1254-induced DNA damage in sperm and all of tissues. Se deficiency aggravated the toxicity by increasing DNA damage caused by Aroclor 1254. Further studies should be performed to clarify the mechanism(s) underlying the protective role of Se status against Aroclor 1254 genotoxicity.

Protective effect of aqueous and ethanolic extracts of Tamarindusindica L. leaf on oxidative stress induced by sodium fluoride in different tissues of rat

Protective effect of aqueous and ethanolic extracts of Tamarindusindica L. leaf on oxidative stress induced by sodium fluoride in different tissues of rat

Highly sensitive determination of fatty acid esters of hydroxyl fatty acids by liquid chromatography-mass spectrometry.

Recently, a new class of endogenous lipids, branched fatty acid esters of hydroxy fatty acids (FAHFAs), was discovered with anti-diabetic and anti-inflammatory effects in mammals. FAHFAs attracted increasing attention because of their critical physiological function. However, accurate quantitation of FAHFAs is still a challenge due to their high structure similarity and low abundance in biological samples. Herein, we developed a highly sensitive method for the determination of 16 FAHFAs (PAHSAs, OAHSAs, SAHSAs and POHSAs) in biological samples by coupling strong anion exchange solid phase extraction (SAX-SPE) with chemical labeling assisted ultra-high performance liquid chromatography/mass spectrometry (SAX-SPE-CL-UHPLC/MS). In the developed method, SAX-SPE was employed to selectively enrich and purify FAHFAs from biological samples. And then a pair of isotope labeling reagents, 2-dimethylaminoethylamine (DMED) and d4-DMED were used to label the purified samples and standard FAHFAs, respectively. The labeled samples were mixed and further subjected to UHPLC/MS analysis. Our results demonstrated that the detection sensitivities of FAHFAs increased by 7-72 folds upon DMED labeling and the limits of detections (LODs) of labeled FAHFAs ranged from 0.01 to 0.14pg. Moreover, a good separation of FAHFAs isomers was achieved on C18 column in a UHPLC system and all FAHFAs could be analyzed in 20min with sharp peak shape. The established method provided substantial sensitivity, high specificity, and broad linear dynamic range (3 orders of magnitude). Using this method, we successfully measured the contents and distribution of FAHFAs in rat white adipose, lung, kidney, thymus, liver and heart tissues. The results showed that 7 FAHFAs (13-, 12-, 9-, 5-PAHSA, 13-, 12- and 9-SAHSA) were observed in different tissues of rat. In addition, we successfully detected the above 7 FAHFAs in human serum samples; and among the 7 FAHFAs, 13-, 9-PAHSA, 13- and 12-SAHSA were found remarkably decreased in human breast cancer serum. The proposed method could be successfully applied for the detection of FAHFAs in various biological samples, which will facilitate the understanding of the physiological functions of FAHFAs.

HPTLC: A Tool for Determination of Curcumin in Mammalian Samples

Curcumin, an important phytoconstituent obtained from Curcuma longa L. (turmeric) is used traditionally in the treatment of various inflammatory diseases like arthritis, stroke and bowel diseases, etc. Despite its many health benefits, instability of curcumin in plasma is a major issue. The retention of curcumin in plasma must be properly evaluated in order to establish its stability in biological systems. The current study presents an HPTLC method undertaken for detection of curcumin and determination of its stability in plasma and different tissues of rats. The plasma and tissue samples were appropriately processed to render them suitable for HPTLC analysis. The method employed HPTLC glass plates precoated with silica gel 60F254 as the stationary phase. The mobile phase developed consisted of chloroform, methanol and glacial acetic acid which successfully gave distinct bands for curcumin with a Rf value of 0.95. This newly developed HPTLC method was found to be reproducible and accurate in quantifying curcumin in mammalian samples. This method was further utilized to efficiently estimate the time for which curcumin is retained in its native form in mammalian tissues and plasma alike.

Relationship between Tissue Distributions of Modified Wuzi Yanzong Prescription () in Rats and Meridian Tropism Theory.

To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription (, MWP) in rats and meridian tropism theory. A high-performance liquid chromatography with Fourier transform-mass spectrometry (HPLC-FT) method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature. Nineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine. The tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.

Evaluation of the Protective Effect of Ethanolic Extract of Plantago major Plant Against CCl4 Induced Genotoxicity and Biochemical Disturbance in Rat

This study was carried out through 2010-2014, seasons on on …fresh herbs of Plantago major plant, which was collected from a private nurseries of El Qanater el Khayreyya, Al- Qaluobia Governorate, Egypt. The aim of this study was to investigate the protective potential of ethanolic crud extract of Plantago major against oxidative stress induced by carbon tetrachloride (CCl4) in different tissues in rats. Our results observed that CCl4 exhibited a significant increase in the levels of serum glucose and lipid profile i.e. total cholesterol, triglyceride and low density lipoprotein cholesterol (LDL) with a significant decrease in the level of high density lipoprotein cholesterol (HDL). Also, CCl4 increase liver function including serum aminotransferases (AST and ALT), alkaline phosphatase (ALPh), total protein, albumin (ALB) and total bilirubin activities and kidney function including the levels of serum urea, uric acid and creatinine amounts. Treatment with ethanolic P. major extract at 100mg/kg b.wt before, with and after treatment with CCl4 significantly prevented all of these typically observed changes . Also, P. major extract statistically significant (P<0.01) inhibit DNA damage induced by CCl4 in bone marrow and sperms of rats. Our findings indicate that P. major has a significant protective effect against CCl4 induced genotoxicity and biochemical changes in rat, which may be due to its antioxidant properties.

Toxicity of chlorpyrifos on protease and glutamate dehydrogenase enzyme activities in albino rats

Present study was aimed to elucidate the pesticide toxicity in rats involves induced abnormalities of the intracellular protein catabolic process by the effect of one of the commonly used organophosphate compound chlorpyrifos on the activities of representative protein catabolising proteases and Glutamate dehydrogenase (GDH) is a one of the regulatory enzyme known to check the deamination process to minimize the ammonia level and plays a significant role in the catabolism of amino acids. The sub lethal stress of chlorpyrifos on important metabolites and enzymes of protein metabolism was investigated in most important tissues like liver, kidney, heart and intestine of albino rats. Sub lethal concentration (1/10th LD50 i.e., 20mg/kg body weight) of chlorpyrifos (Organophosphate) on the enzyme parameters of albino rats were analysed after single, double and multiple dose of exposure. The increased protease activities in the different tissues of rat indicate the damage caused due to impairment of energy supply and proteases activity indicates higher protein degradation. Therefore, the proteins are denatured leading to more activation of proteases. The elevated GDH activity levels indicate its contribution to ammonia production and glutamate oxidation during chlorpyrifos toxicity.

Analysis of the distribution of organic compounds and drugs between biological tissues in the framework of solute partitioning in aqueous two-phase systems.

Partition coefficients of non-ionic essentially nonpolar compounds between air and rat biological tissues and between blood and other tissues were examined and found to be linearly interrelated according to the previously established equation for partition coefficients of solutes in aqueous two-phase systems: log Kblood-tissue-1 = k0 + k1 log Kblood-tissue-2 + k2 log Kblood-tissue-3, where k0, k1, and k2 are constants. Analysis of partition coefficients of amphiphilic and ionizable drugs between blood and different tissues in rats in vivo showed that the above relationship holds for the blood-tissue partition coefficients of these compounds as well. The data obtained indicate that distribution of organic compounds between different biological tissues may be considered in the framework of solute partitioning in aqueous two-phase systems, and imply that aqueous media in different tissues have different solvent properties, and compound-water interactions in these media may respond to different environments governed by the tissue composition.

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum.

Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted N-glycans with terminal mannose residues, Galβ1-4GlcNAc (LacNAc) and Galβ1-4(Fucα1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAcβ1-4(GlcNAcβ1)n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAcβ1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage- and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection.

English

Genetically modified (GM) food crops are considered to have the potential of providing food security especially in developing countries. Scientists have raised concern over the hazards associated with the consumption of genetically modified organisms (GMOs). One of these hazards, which have great controversy reports, is the possible horizontal gene transfer from GM-food or feed to human or animal tissues. Many researches were conducted to investigate the presence of some transgenic sequences in animal tissues fed on GM- crops. Many of the inserted genes in the GM-crops are under the control of the promoter of the Cauliflower mosaic virus (CaMVP35S) and produce insecticidal proteins. Health hazards are suggested to accompany the ingestion of this promoter. CaMVP35S can function in a wide range of organisms (plants and animals). It has also been demonstrated that the CaMV-P35S promoter sequence can convert an adjacent tissue- and organ-specific gene promoter into a globally active promoter. The present work was conducted to evaluate the possibility of horizontal gene transfer from a diet containing DNA segments from Cauliflower mosaic virus -35S promoter (CaMVP-35S) to the cells of different organs of rats fed for three months on diets containing genetically modified components. Analysis of the results revealed that: 1) ingested fragments from the CaMV-35S promoter incorporated into blood, liver, and brain tissues of experimental rats, 2) The total mean of transfer of GM target sequences increased significantly by increasing the feeding durations, and 3) The affinity of different transgenic fragments from the ingested GM-diet, to be incorporated into the different tissues of rats varied from one target sequence to the other.&nbsp; &nbsp; Key words: Genetic modification, transgenic sequences, GM-crops, gene flow, CaMV P-35S.&nbsp; &nbsp

Synergistic effect of Se-methylselenocysteine and vitamin E in ameliorating the acute ethanol-induced oxidative damage in rat

The present study was conduced to investigate the synergistic effects of combined treatments with Se-methylselenocysteine (SeMSC) and vitamin E (Vit E) in reversing oxidative stress induced by ethanol in serum and different tissues of rats. Sixty female rats were randomly divided into six groups for 30 days’ consecutive pretreatments as followed: control (I), physiological saline (II), 2.8μgkg−1 Se as SeMSC (III), 2.8μgkg−1 Se as sodium selenite (Na2SeO3, IV), 5mgkg−1 α-tocopherol as α-tocopherol acetate (Vit E, V), 5mgkg−1 α-tocopherol as α-tocopherol acetate and 2.8μgkg−1 Se as SeMSC (VI). All animals in groups II–VI were treated by ethanol treatment to cause oxidative stress. After 6h of ethanol treatment, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), the contents of total antioxidant capacity (T-AOC), malondialdehyde (MDA), glutathione (GSH) and carbonyl protein (CP) in the serum, liver, heart and kidney were measured. The result showed that the individual SeSMC, Na2SeO3 and vitamin E could effectively increase the SOD, T-AOC, GSH-Px and GSH contents as well as significantly decrease the MDA and CP concentrations in the tissues of ethanol-induced rats. At the same dose on different forms of Se, SeMSC showed greater antioxidant activity than Na2SeO3. Moreover, group VI (SeMSC and α-tocopherol acetate) showed much better antioxidant activity than individual group III (SeMSC) and V (α-tocopherol acetate) due to the synergistic effect.

Effects of creatine supplementation associated with resistance training on oxidative stress in different tissues of rats

BackgroundCreatine supplementation is known to exert an effect by increasing strength in high intensity and short duration exercises. There is a hypothesis which suggests that creatine supplementation may provide antioxidant activity by scavenging Reactive Oxygen Species. However, the antioxidant effect of creatine supplementation associated with resistance training has not yet been described in the literature. Therefore, we investigated the effect of creatine monohydrate supplementation associated with resistance training over maximum strength gain and oxidative stress in rats.MethodsForty male Wistar rats (250-300 g, 90 days old) were randomly allocated into 4 groups: Sedentary (SED, n = 10), Sedentary + Creatine (SED-Cr, n = 10), Resistance Training (RT, n = 10) and Resistance Training + Creatine (RT-Cr, n = 10). Trained animals were submitted to the RT protocol (4 series of 10–12 repetitions, 90 second interval, 4 times per week, 65% to 75% of 1MR, for 8 weeks).ResultsIn this study, greater strength gain was observed in the SED-Cr, RT and RT-Cr groups compared to the SED group (P < 0.001). The RT-Cr group showed a higher maximum strength gain when compared to other groups (P < 0.001). Creatine supplementation associated with resistance training was able to reduce lipoperoxidation in the plasma (P < 0.05), the heart (P < 0.05), the liver (P < 0.05) and the gastrocnemius (P < 0.05) when compared to control groups. However, the supplementation had no influence on catalase activity (CAT) in the analyzed organs. Only in the heart was the CAT activity higher in the RT-Cr group (P < 0.05). The activity of superoxide dismutase (SOD) was lower in all of the analyzed organs in the SED-Cr group (P < 0.05), while SOD activity was lower in the trained group and sedentary supplemented group (P < 0.05).ConclusionsCreatine was shown to be an effective non-enzymatic antioxidant with supplementation alone and also when it was associated with resistance training in rats.

Differences in metabolic and mitogenic signalling of insulin glargine and insulin aspart B10 in rats

Aims/hypothesisIn vitro, insulin glargine (A21Gly,B31Arg,B32Arg human insulin) has an insulin receptor (IR) profile similar to that of human insulin, but a slightly higher affinity for the IGF-1 receptor (IGF1R). Insulin aspart B10 (B10Asp human insulin) (AspB10), the only insulin analogue with proven carcinogenic activity, has a greater affinity for IGF1R and IR, and a prolonged IR occupancy time. The pharmacological and signalling profile of therapeutic and suprapharmacological doses of glargine were analysed in different tissues of rats, and compared with human insulin and AspB10.MethodsMale Wistar rats were injected s.c. with human insulin or insulin analogue at doses of 1 to 200 U/kg, and the effects on blood glucose and the phosphorylation status of IR, IGF1R, Akt and extracellular signal-regulated protein kinase 1/2 in muscle, fat, liver and heart samples were investigated.ResultsGlargine, AspB10 and human insulin lowered blood glucose, with the onset of action delayed with glargine. Glargine treatment resulted in phosphorylation levels of IR and Akt that were comparable with those achieved with human insulin, although delayed in time in some tissues. AspB10 treatment resulted in at least twofold higher phosphorylation levels and significantly longer duration of IR and Akt phosphorylation in most tissues. None of the insulin treatments resulted in detectable IGF1R phosphorylation in muscle or heart tissue, whereas intravenous injection of IGF-1 increased IGF1R phosphorylation.Conclusions/interpretationThe IR signalling pattern of AspB10 in vivo is distinctly different from that of human insulin and insulin glargine, and might challenge the notion that activation of IGF1R plays a role in the observed carcinogenic effect of AspB10.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-2923-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Effect of long term administration of resveratrol on lipid concentration in selected organs and liver’s histology in rats fed high fructose diet

The aim of this study was to evaluate the effect of long term administration (4months) of resveratrol (RSV) with high fructose (HF) diet (63%) on selected biochemical parameters and lipids content in different tissues of rats. Lipid profile in serum of rats was not affected by the addition of resveratrol to the experimental diets. The concentration of tiobarbituric acid reactive substances (TBARS; expressed as the melanodialdehyde – MDA equivalents) was significantly lower in the serum of rats fed HF diet with the addition of 0.04% and 0.06% of resveratrol. Crude lipids content in hearts was lower in rats fed with HF diet with the addition of 0.06% RSV. The concentration of lipids was also significantly lower in the liver of animals fed with HF diet with the addition of 0.04% or 0.06%. These results indicated that resveratrol significantly decreased fat accumulation and oxidative stress in rats fed with a high fructose diet.

Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

We report strong somatic and germ line expression of LINE RNAs in eight different tissues of rat by using a novel ~2.8 kb genomic PstI-LINE DNA (P1-LINE) isolated from the rat brain. P1-LINE is present in a 93 kb LINE-SINE-cluster in sub-telomeric region of chromosome 12 (12p12) and as multiple truncated copies interspersed in all rat chromosomes. P1-LINEs occur as inverted repeats at multiple genomic loci in tissue-specific and mosaic patterns. P1-LINE RNAs are strongly expressed in brain, liver, lungs, heart, kidney, testes, spleen and thymus into large to small heterogeneous RNAs (~5.0 to 0.2 kb) in tissue-specific and dynamic patterns in individual rats. P1-LINE DNA is strongly methylated at CpG-dinucleotides in most genomic copies in all the tissues and weakly hypomethylated in few copies in some tissues. Small (700–75 nt) P1-LINE RNAs expressed in all tissues may be possible precursors for small regulatory RNAs (PIWI-interacting/piRNAs) bioinformatically derived from P1-LINE. The strong and dynamic expression of LINE RNAs from multiple chromosomal loci and the putative piRNAs in somatic tissues of rat under normal physiological conditions may define functional chromosomal domains marked by LINE RNAs as long noncoding RNAs (lncRNAs) unrestricted by DNA methylation. The tissue-specific, dynamic RNA expression and mosaic genomic distribution of LINEs representing a steady-state genomic flux of retrotransposon RNAs suggest for biological role of LINE RNAs as long ncRNAs and small piRNAs in mammalian tissues independent of their cellular fate for translation, reverse-transcription and retrotransposition. This may provide evolutionary advantages to LINEs and mammalian genomes.

Pharmacokinetics and Tissue Distribution Study of Tryptanthrin in Rats by RP-HPLC with DAD Detector

A simple RP-LC-UV method was established for the determination of tryptanthrin in plasma and different tissues of rats. The separation was achieved by HPLC on a C18 column with a mobile phases composed of acetonitrile–water (47:53, v/v), UV detection was used at 251 nm. Good linearity was found between 0.0183–1.1712 μg mL−1 (r 2 = 0.999) for plasma and 0.0937–1.7568 μg mL−1 for the tissue samples, respectively (r 2 ≥ 0.9932). The intra- and inter-day precisions expressed as the relative standard deviation for the method were 0.92–6.01 and 1.06–9.11 %, respectively. The relative recoveries of tryptanthrin ranged from 95.26 to 97.89 % for plasma and 82.55 to 114.99 % for tissue homogenates (except heart). The developed method was successfully applied to the pharmacokinetics and tissue distribution research after orally administration of a 56-mg kg−1 dose of tryptanthrin to healthy SD rats. The main pharmacokinetics distribution results showed that liver, lung, small intestine, and large intestine were the major distribution tissues of tryptanthrin in rats, and that tryptanthrin had difficulty in crossing the blood–brain barrier.

Size effect of gold nanoparticles on various trace elements levels in different tissues of rats

Despite the many benefits of nanotechnology, some studies have indicated that nanoparticles (NPs) may cause adverse effects, which may be attributed to size, shape, particles number, surface area and unique properties. Very little information exists on gold nanoparticles (GNPs) toxicity in vivo and other biochemical effects. The aim of the present study was to elucidate the size effect of GNPs on various trace elements levels in several tissues of rats. The experimental rats were divided into control and 3 groups (G1A, G2A and G3A; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion of 0.05 ml of GNPs for 3 days). To investigate the size effect of 10, 20 and 50 nm GNPs on Calcium (Ca), Copper (Cu), Iron (Fe) and Zinc (Zn) elements in several tissues of rats, 0.05 ml dose of GNPs was intraperitonealy injected into rats for period of 3 days to identify the toxicity and tissue distribution of various trace elements levels in vivo. All the sizes of GNPs used in this study caused a significant decrease in Ca and Zn concentrations in liver, lung, heart, kidney tissues and blood compared with the control. The 10 and 20 nm GNPs caused a significant increase in Cu concentration in liver, lung, heart, kidney and blood compared with the control. The 50 nm GNPs caused a significant increase in Cu concentration in liver, lung, heart and kidney tissues compared with the control while 50 nm GNPs did not cause significant change in blood Cu concentration compared with the control. The 10 and 20 nm GNPs caused a significant increase in Fe concentration in liver, lung, heart and kidney tissues of rats. The 50 nm GNPs caused a significant increase in Fe concentrations in liver, heart, kidney tissues and blood of rats while it decreased in lung tissue compared with the control. 10 and 20 nm GNPs may be an effective inducer of oxidative stress which was evident by the fact that they caused a decrease in the cellular Ca and Zn concentrations coupled with the increase in the concentrations of Fe and Cu. Key words: Gold nanoparticles, size, several tissues, trace elements, rats.

Repeated Oral Dose Toxicity of Iron Oxide Nanoparticles: Biochemical and Histopathological Alterations in Different Tissues of Rats

Iron oxide (Fe2O3) nanoparticles are widely used in different fields of nanotechnology. However, studies on its toxicological effects in humans and the environment are scarce. Therefore in this investigation 28 days repeated dose oral toxicity studies were conducted on Fe2O3-30 nanoparticles and its counterpart Fe2O3-Bulk with special reference to target biochemical enzymes and histopathological changes in different tissues of female albino Wistar rats. The alterations observed after Fe2O3-30 treatment in various tissues of exposed rats were dose dependent. Low dose was less effective than medium and high doses with low dose demonstrating "no observed adverse effect" (NOAEL). Further, high dose treated rats showed toxic sign and symptoms but no mortality. Due to the repeated doses of Fe2O3-30 nanoparticles, significant inhibition was observed in total, Na(+)-K+, Mg2+ and Ca(2+)-ATPases in brain of exposed rats. Similarly, significant inhibition was recorded in RBC and brain acetylcholinesterase indicating that both synaptic transmission and nerve conduction were affected by this compound. Fe2O3-30 significantly increased aspartate amino transferase, alanine amino transferase and lactate dehydrogenase in serum and liver, whereas, these enzymes were significantly decreased in kidney indicating tissue necrosis and possible leakage of these enzymes into the blood stream. Increased levels of these enzymes in liver as well as in serum might be an adaptive mechanism due to the stress of iron nanoparticles. High dose treated rats of Fe2O3-30 showed dilated central vein, perivascular round cell collections in liver along with focal areas of necrosis, whereas kidney showed focal tubular damage and red pulp congestion, whereas prominent white pulp indices were observed in spleen. However, histopathological analysis of heart and brain tissues failed to show any adverse changes in their architecture exposed to repeated doses of Fe2O3-30 when compared with controls. Fe2O3-Bulk did not induce any adverse effects in either biochemical parameters or histopathology in the treated rats and the changes observed were near to controls and mostly insignificant, indicating that the counter part of nanoparticles i.e., bulk material is less potent than the nanoparticles in causing toxicity in the exposed animals. These results suggested that as particle size decreases, this iron nanoparticle showed increased toxicity, even though the same material is relatively inert in bulk form. The changes observed in these target enzyme activities could be useful as biomarkers of exposure to nanoparticles.