Alterations In Different Tissues Research Articles

Data-dependent and -independent acquisition lipidomics analysis reveals the tissue-dependent effect of metformin on lipid metabolism.

Despite the well-recognized health benefits, the mechanisms and site of action of metformin remains elusive. Metformin-induced global lipidomic changes in plasma of animal models and human subjects have been reported. However, there is a lack of systemic evaluation of metformin-induced lipidomic changes in different tissues. Metformin uptake requires active transporters such as organic cation transporters (OCTs), and hence, it is anticipated that metformin actions are tissue-dependent. In this study, we aim to characterize metformin effects in non-diabetic male mice with a special focus on lipidomics analysis. The findings from this study will help us to better understand the cell-autonomous (direct actions in target cells) or non-cell-autonomous (indirect actions in target cells) mechanisms of metformin and provide insights into the development of more potent yet safe drugs targeting a particular organ instead of systemic metabolism for metabolic regulations without major side effects. To characterize metformin-induced lipidomic alterations in different tissues of non-diabetic male mice and further identify lipids affected by metformin through cell-autonomous or systemic mechanisms based on the correlation between lipid alterations in tissues and the corresponding in-tissue metformin concentrations. A dual extraction method involving 80% methanol followed by MTBE (methyl tert-butyl ether) extraction enables the analysis of free fatty acids, polar metabolites, and lipids. Extracts from tissues and plasma of male mice treated with or without metformin in drinking water for 12days were analyzed using HILIC chromatography coupled to Q Exactive Plus mass spectrometer or reversed-phase liquid chromatography coupled to MS/MS scan workflow (hybrid mode) on LC-Orbitrap Exploris 480 mass spectrometer using biologically relevant lipids-containing inclusion list for data-independent acquisition (DIA), named as BRI-DIA workflow followed by data-dependent acquisition (DDA), to maximum the coverage of lipids and minimize the negative effect of stochasticity of precursor selection on experimental consistency and reproducibility. Lipidomics analysis of 6 mouse tissues and plasma allowed a systemic evaluation of lipidomic changes induced by metformin in different tissues. We observed that (1) the degrees of lipidomic changes induced by metformin treatment overly correlated with tissue concentrations of metformin; (2) the impact on lysophosphatidylcholine (lysoPC) and cardiolipins was positively correlated with tissue concentrations of metformin, while neutral lipids such as triglycerides did not correlate with the corresponding tissue metformin concentrations; (3) increase of intestinal tricarboxylic acid (TCA) cycle intermediates after metformin treatment. The data collected in this study from non-diabetic mice with 12-day metformin treatment suggest that the overall metabolic effect of metformin is positively correlated with tissue concentrations and the effect on individual lipid subclass is via both cell-autonomous mechanisms (cardiolipins and lysoPC) and non-cell-autonomous mechanisms (triglycerides).

Increased Cardiovascular Disease Risk in Adult Offspring with Prenatal Opioid Exposure Is Associated with Endogenous Opioid Peptide Dysregulation

Parental drug abuse and dysfunctional households during childhood increase the risk for cardiovascular disease (CVD) later in life. Chronic opioid exposure and opioid use disorder (OUD) are associated with a 2-fold increased risk of CVD and a 16% increase in coronary artery disease. OUD among pregnant women is an understudied area related to the opioid epidemic, causing a 5-fold increase in neonatal opioid withdrawal syndrome (NOWS) incidence. In former studies, we subjected female rats to two models of maternal opioid exposure: 1) morphine sulfate during gestation or 2) fentanyl citrate during preconception and gestation. At birth, female and male opioid-exposed offspring showed normal birth weight compared with vehicle-exposed offspring while displaying NOWS-like somatic withdrawal signs after parturition. As adults, in utero opioid-exposed offspring displayed increased mean arterial pressure, sympathetic activation, and CVD risk factors. Prenatal exposure to opioids has been shown to dysregulate the endogenous opioid peptides (EOPs) and alter behavioral outcomes later in life, but the transplacental effects of opioids on blood pressure regulation remain understudied. Therefore, this study aimed to assess whether adult offspring with prenatal opioid exposure display changes in 1) the expression of the EOP proenkephalin (PENK) in brain regions known to control the sympathetic outflow (Paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM)), heart, kidneys, and liver; 2) the plasma levels of EOPs (PENK, enkephalin, prodynorphin and dynorphin); and 3) the fentanyl plasma clearance (pharmacokinetics). Protein was extracted from tissues for western blot analysis using the primary antibody for PENK (1:1000, Invitrogen). In opioid-exposed offspring, PENK protein expression was reduced in RVLM (0.55±0.06 vs. 0.36±0.01, AU) and PVN (1.56±0.09 vs. 1.08±0.08, AU), showing a ~35% and ~31% reduction, respectively (n=4-5, p<0.05). In the heart, PENK protein expression was not statistically different in opioid-exposed offspring compared with vehicle-exposed offspring. However, in the kidneys (0.72±0.09 vs. 1.16±0.10, AU) and liver (0.40±0.06 vs. 0.60±0.05, AU), PENK protein expression showed a 61% and 50% increase only in male opioid-exposed offspring compared to vehicle-exposed offspring (n=6-8, p<0.05). None of the plasma circulating EOP levels measured by ELISA were affected by prenatal opioid exposure. Fentanyl clearance in plasma (0, 15, 30, 60, 120, 360,1440 mins) following a fentanyl injection (20ug/kg, sc.) was not different between adult vehicle and opioid-exposed offspring, indicating potential pharmacodynamic alterations secondary to prenatal opioid exposure. As EOPs exert inhibitory effects on adrenergic signaling, our data indicate that prenatal exposure to opioids may induce a permanent downregulation of EOPs in the central nervous system and thus contributing to increasing the sympathetic tone and desensitize the acute depressor responses to opioid peptides, suggesting that EOPs may be critical for blood pressure regulation. However, peripheral expression of PENK seems to reflect pathophysiological alterations in different tissues since elevated PENK level is used in clinical settings as a marker to assess the severity of tissue damage in the liver and kidneys. This study was funded by 1013177615 (NRPA-UK), 1013400001 (SUGAR-UK) and 1013171360 (DPNS-UK). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

LIF spectroscopy of epithelial tissues: Assay of structural changeover due to the cancer progression.

Most of the human cancers occur in epithelial tissues containing basic cells with different shapes, and not only do the spectral properties of the tissue pigments alter due to cancer, but the cellular architecture also change. However, in optical diagnosis of the cancerous tissues, attention has been paid to the spectral changeover of native chromophores as bio-markers. Here, we have attempted to assay the structural alterations of the epithelial tissues during the cancer progression utilizing Laser induced fluorescence (LIF) spectroscopy as a fast, sensitive and easy-to-use method. In this regard, angular dependence of the LIF spectral features of the healthy and cancerous epithelial tissues (soaked in Rhodamine 6G solution) from three different human organs i. e. uterus, colon and kidney with distinct microstructures have been examined. In general, both wavelength and intensity at the peak of the LIF spectra depend on the tissue orientation and the angle of detection respect to the laser beam direction. Those optical parameters also demonstrate distinctive alterations in different tissues that is explicated based on the morphological alteration of the epithelial cells in each carcinoma type provided by pathology data.

Assessment toxic effects of exposure to 3-indoleacetic acid via hemato-biochemical, hormonal, and histopathological screening in rats

The current study purposed to investigate the 3-indoleacetic acid (IAA) possible adverse impacts on hematological parameters, hepatorenal function, cardiac, and skeletal muscles as well as testes of rats and histopathological alterations of respective organs and to determine the extent of reversing any adverse impacts occurred in animals after IAA withdrawal. Rats were exposed orally to 500 mg/kg BW by gastric intubation once daily for 14 days, after which one-half was sacrificed and the remaining half left for a further 14 days without IAA exposure. The exposure of rats to IAA produced anemia, leukopenia, neutrophilia, lymphopenia, and a significant increase in activities of serum transaminase, gamma-glutamyl transferase, creatine kinase-myocardial band, creatine kinase-muscle type, and levels of serum creatinine, sodium, chloride, and potassium. Furthermore, serum levels of testosterone, gonadotropins, and leptin significantly declined. The changes in most of measured parameters continued after IAA withdrawal. Histopathological alterations in different tissues supported these changes. In conclusion, subacute exposure to IAA at a high concentration could exert hematotoxicity and toxic effects on many soft organs and its withdrawal led to incomplete recovery of animals. Thus, IAA should be used cautiously as extensive use of it at high concentrations can cause harmful effects on the environment, animals and human beings.

Low salinity induced challenges in the hardy fish Heteropneustes fossilis; future prospective of aquaculture in near coastal zones

The groundwater in coastal and abiding zones is experiencing alarmingly growing levels of salinity that might be small in absolute terms. Several reasons may contribute for retrogression of groundwater quality and the most concerning issue is they can critically distress the inhabitants. This notion encouraged us to comprehensively investigate the salinity tolerance range and effects of sub-lethal salinity on various attributes such as the growth pattern (morphometric and feed intake), haematology, histo-architecture and generation of oxidative stress in different tissues of Heteropneustes fossilis, a coastal zone hardy fish that has high market demand. The fish were exposed to sub-lethal salinity i.e. 3, 6 and 9 ppt for 45 days against a control set (tap water, ~0 ppt) under constantly monitored pH, temperature, dissolved oxygen and alkalinity. The fish can tolerate a narrow salinity range although correlation and discriminant function analyses among the computed parameters indicate that sub-lethal low salinity strongly modulates the fish physiology. Decline in the body weight, feed intake, specific growth rate and changes in morphometry coupled with histological alterations in different tissues were observed with the increase in level of sub-lethal salinity. The significant alterations in the measured parameters substantiated an overall decline in growth of the fish at 9 ppt. Significant loss in haemoglobin content, RBC and eosinophil counts accompanied by a rise in neutrophil count was also observed at higher salinities. The lipid peroxide level under higher salinities was comparatively higher than the control. Disruption in the typical histo-architecture in its muscle, gill and liver tissues was observed at higher salinities, possibly due to the generation of oxidative stress and/or osmotic imbalances in the respective tissues. In conclusion, the H. fossilis can satisfactorily grow in low salinities up to 6 ppt and critically beyond the range till 9 ppt. Therefore, the study of compromised physiology due to the toxic effects of altered salinity under changing climatic conditions and anthropogenic activities in the inhabitants especially in lower vertebrate hardy fish models is a major concern in aquaculture prospect. The development of this study on the transcriptional and translational level could provide access to unsolved problems related to aquaculture. Further it also suggests that a) it is indispensable to maintain optimal freshwater quality in coastal and allied zone globally in coming decades, b) introduction of saline tolerant hardy fish species and development of appropriate aquaculture practices based upon the altered physiology in the concerned regions.

Tissue Bioaccumulation and Toxicopathological Effects of Cadmium and Its Dietary Amelioration in Poultry-a Review.

Cadmium (Cd) has been recognized as one of the most toxic heavy metals, which is continuously discharged into environments through anthropogenic (industrial activities, fertilizer production, and waste disposal) and natural sources with anthropogenic sources contributing greater than the natural sources. Therefore, Cd concentration sometimes increases in feeds, fodders, water bodies, and tissues of livestock including poultry in the vicinity of the industrial areas, which causes metabolic, structural, and functional changes of different organs of all animals. In poultry, bioaccumulation of Cd occurs in several organs mainly in the liver, kidney, lung, and reproductive organs due to its continuous exposure. Intake of Cd reduces growth and egg laying performance and feed conversion efficiency in poultry. Chronic exposure of Cd at low doses can also alter the microscopic structures of tissues, particularly in the liver, kidney, brain, pancreas, intestine, and reproductive organs due to increased content of Cd in these tissues. Continuous Cd exposure causes increased oxidative stress at cellular levels due to over-production of reactive oxygen species, exhausting antioxidant defense mechanisms. This leads to disruption of biologically relevant molecules, particularly nucleic acid, protein and lipid, and subsequently apoptosis, cell damage, and necrotic cell death. The histopatholocal changes in the liver, kidneys, and other organs are adversely reflected in hemogram and serum biochemical and enzyme activities. The present review discusses about Cd bioaccumulation and histopathological alterations in different tissues, pathogenesis of Cd toxicity, blood-biochemical changes, and its different ameliorative measures in poultry.

Biochemical and Histopathological Alterations in Different Tissues of Rats Due to Repeated Oral Dose Toxicity of Cymoxanil.

Simple SummaryCymoxanil is a broad-spectrum fungicide used to protect many fruits, vegetables, and field crops against several fungal diseases. Investigating the potential hazards and toxicological effects of this fungicide is very important as cymoxanil can be a major human health concern. The present study investigated the effect of repeated oral doses of cymoxanil on different tissues of treated rats by measuring different biochemical parameters and investigating the histopathological changes. Interestingly, our study reported a dose-dependent effect of cymoxanil that was combined with marked alteration on biochemical enzymes. Moreover, the alteration was combined with marked histopathological changes in various tissues of treated rats, mainly liver, brain, and kidney tissues. Our study collectively reveals that cymoxanil can be a source of major concern for human health with respect to long-term and low dose exposure.Evaluating potential adverse health impacts caused by pesticides is an important parameter in human toxicity. This study focuses on the importance of subchronic toxicity assessment of cymoxanil fungicide in rats with special reference to target biochemical enzymes and histopathological changes in different tissues. In this regard, a 21-day toxicity study with repeated cymoxanil oral doses was conducted. It has been shown that low doses (0.5 mg/kg) were less effective than medium (1 mg/kg) and high (2 mg/kg) doses. Moreover, high dose dose-treated rats showed piecemeal necrosis in the liver, interstitial nephritis and tubular degeneration in the kidneys, interstitial pneumonia and type II pneumocyte hyperplasia in the lungs, gliosis, spongiosis, and malacia in the brain, and testicular edema and degeneration in the testes. Cymoxanil significantly increased AST, ALT, and ALP in serum and liver, indicating tissue necrosis and possible leakage of these enzymes into the bloodstream. Creatinine levels increased, indicating renal damage. Similarly, significant inhibition was recorded in brain acetylcholinesterase, indicating that both synaptic transmission and nerve conduction were affected. Importantly, these histopathological and biochemical alterations were dose-dependent. Taken together, our study reported interesting biochemical and histopathological alterations in different rat tissues following repeated toxicity with oral doses of cymoxanil. Our study suggests future studies on different pesticides at different concentrations that would help urge governments to create more restrictive regulations concerning these compounds’ levels.

S-Methylcysteine (SMC) Ameliorates Intestinal, Hepatic, and Splenic Damage Induced by Cryptosporidium parvum Infection Via Targeting Inflammatory Modulators and Oxidative Stress in Swiss Albino Mice.

Cryptosporidiosis has been proposed to be one of the major causes of diarrhoeal disease in humans worldwide that possesses zoonotic concern. Thereby, this study investigated the potential effects of s-Methylcysteine (SMC) on the parasite in vivo followed by the measurement of cytokines, oxidative stress parameters, and an investigation of the major histopathological changes. Sixty male Swiss albino mice weighing 20–25 g were allocated equally into five groups and orally administered saline only (control), SMC only (SMC50) (50 mg/kg b.w.), and 104 Cryptosporidium parvum oocysts per mouse via an esophageal tube (C + ve untreated). The fourth and fifth groups (C + SMC25, C + SMC50) administrated 104 C. parvum oocysts combined with SMC25 (low dose) and 50 (high dose) mg/kg b.w., respectively. At days 7 and 14 post-infection (PI), the feces was collected from each group in order to count C. parvum oocysts. After two weeks of treatment, the animals were euthanized and the serum was collected for biochemical analysis. Next, the intestinal, spleen, and liver sections were dissected for histopathological examination. The results revealed lower oocyst numbers in the C + SMC25 and C + SMC50 groups compared to the infected untreated group. Moreover, higher doses of SMC treatment significantly reduced the enteritis induced by C. parvum in a dose-dependent manner. The hepatic lesions were also mitigated as demonstrated in C + SMC25 and C + SMC50 groups unlike the infected group via lowering the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes and increasing albumin and globulin serum levels. SMC administration also reduced cytokines production (SAP, TNF-α, IL-6, and IFN-γ) mediated by Cryptosporidium infection in contrast to the infected untreated group. There were marked lymphoid depletion and amyloidosis observed in the infected untreated group, while the treated groups showed obvious increase in the lymphoid elements. Moreover, the scoring of intestinal parasites, hepatic, and splenic lesions in the SMC-treated groups exhibited significantly lower pathological lesions in different organs in a dose-dependent manner, compared to the infected untreated group. Our results also revealed a significant change in the malondialdehyde content with an elevation of glutathione and superoxide dismutase in the intestines collected from C + SMC25 and C + SMC50 mice relative to the untreated group. Taken together, our results indicated that SMC could be a promising effective compound for treating and declining C. parvum infestation via restoring structural alterations in different tissues, enhancing antioxidant enzymes, and suppressing the cytokines liberation.

MATERNAL AND FETAL TOXICITY-INDUCED BY NICKEL OXIDE NANOPARTICLES ADMINISTRATION IN ALBINO RATS DURING GESTATION

Objective: Despite the widespread of nickel oxide nanoparticles (NiO NPs) and their benefits in all fields, they have many negative effects on human life, especially expectant mothers and their fetus. The purpose of this study was to investigate the possible maternal and developmental toxicity-induced by NiO NPs administration during gestation.
 Methods: Three groups of pregnant rats were administered orally during days 5–19 of gestation, the pregnant rats were haphazardly designed into three groups (six rat/group), as follows: Control group and NiO NPs administered groups, low (4 mg/kg), and high (8 mg/kg) doses.
 Results: NiO NPs administration resulted in severe maternal and developmental toxicity which included reduction in uterine weight, mother weight gain, the average weight of placenta, the number corpora lutea, implantation sites, and the number of live fetuses. Furthermore, high pre/ postimplantation, fetal growth retardation, and morphological and skeletal anomalies, an elevation in liver and brain DNA damage in both mother and fetus, and histopathological alterations in different tissues (placenta, liver, kidney, and brain) of pregnant rats and fetuses. Lipid peroxidation showed a significant elevation in maternal, fetal liver, and brain tissues of NiO NPs ‐administered rats. Furthermore, glutathione content and catalase activity were decreased in both tissues of NiO NPs‐administered rats.
 Conclusion: Finally, the detrimental impacts of NiO NPs in dams and fetuses probably through its potential generation of reactive oxygen species.

Experimental mummification-In the tracks of the ancient Egyptians.

Understanding natural and artificial postmortem alterations in different tissues of the human body is essential for bioarchaeology, paleogenetics, physical anthropology, forensic medicine, and many related disciplines. With this study, we tried to gain a better understanding of tissue alterations associated with the artificial mummification techniques of ancient Egypt, in particular for mummified visceral organs. We used several entire porcine organs and organ sections (liver, lung, stomach, ileum, and colon), which provided a close approximation to human organs. First, we dehydrated the specimens in artificial natron, before applying natural ointments, according to the ancient literary sources and recent publications. We periodically monitored the temperature, pH value, and weight of the specimens, in addition to radiodensity and volumetric measurements by clinical computed tomography and sampling for histological, bacteriological, and molecular analyses. After seven weeks, mummification was seen completed in all specimens. We observed a considerable loss of weight and volume, as well as similar courses in the decay of tissue architecture but varying levels of DNA degradation. Bacteriologically we did not detect any of the initially identified taxa in the samples by the end of the mummification process, nor any fungi. This feasibility study established an experimental protocol for future experiments modeling ancient Egyptian mummification of visceral organs using human specimens. Understanding desiccation and mummification processes in non-pathological tissues of specific visceral organs may help to identify and interpret disease-specific alterations in mummified tissues in ancient Egyptian canopic jars and organ packages contained in whole mummies.

Oral toxicity of arjunolic acid on hematological, biochemical and histopathological investigations in female Sprague Dawley rats.

BackgroundArjunolic acid (AA) is a potent phytochemical with wider pharmacological activities. Despite potential medicinal properties on various in vitro and in vivo studies, there is still a dearth of scientific data related to its safety profile and toxicological parameters. The current study aimed to investigate acute toxicity of AA in normal female Sprague Dawley rats.MethodsIn this study, AA was administered orally at an individual dose of 300 and 2000 mg/kg body weight to group 1 and 2 respectively, while group 3 served as normal control. All the animals were observed for 2 weeks to determine any behavioral and physical changes. On day 15, blood was collected for hematological and biochemical investigation, later animals from all the three groups were euthanized to harvest and store essential organs for histopathological analysis. Four different staining techniques; hematoxylin and eosin, Masson trichrome, Periodic acid Schiff and Oil O Red were used to investigate any alterations in different tissues through microscopical observation.ResultsThe results of the study showed no morbidity and mortality at two different dosage of AA treatment. Daily food & water intake, body weight, relative organ weight, hematological and biochemical parameters were detected to be normal with no severe alteration seen through microscopical investigation in the structure of harvested tissues. Our findings support the safety profile of AA, which was well tolerated at higher dose. Thus, an in-detail study on the subacute disease model is warranted.

The Perennial Use of the Green Fluorescent Protein Marker in a Live Vaccinia Virus Ankara Recombinant Platform Shows No Acute Adverse Effects in Mice.

Recombinant virus vectors represent a promising strategy for vaccine research. Among available viral vectors, members of the Poxviridae family-especially the modified Vaccinia virus Ankara (MVA)-stand out as immunogenic and safe vaccine platforms. Because MVA usually does not produce plaques in cell culture, visible selection markers such as the green fluorescent protein (GFP) are frequently incorporated into the constructions in order to facilitate the recognition of recombinants. However, these genetic markers have to be removed before any clinical trial. Here, we evaluated the acute responses generated in mice immunized with a MVA vector in which the GFP marker was not removed. We observed no differences in neutrophil, monocyte, or total leucocyte recruitment among animals inoculated with MVA or MVA-GFP. Likewise, there were no differences in neutrophil activation between mice groups. Hepatic functions were not altered in either MVA or MVA-GFP-inoculated mice, and we observed no histopathological alterations in different tissues from virus-inoculated animals. In conclusion, the presence of GFP is innocuous to immunized animals and do not alter acute physiopathological responses to the MVA vector. We suggest that keeping the GFP marker may be a good strategy for vaccine development, production, and evaluation.

Mitochondrial activity in different regions of the brain at the onset of streptozotocin-induced diabetes in rats.

Diabetes affects a variety of tissues including the central nervous system; moreover, some evidence indicates that memory and learning processes are disrupted. Also, oxidative stress triggers alterations in different tissues including the brain. Recent studies indicate mitochondria dysfunction is a pivotal factor for neuron damage. Therefore, we studied mitochondrial activity in three brain regions at early type I-diabetes induction. Isolated mitochondria from normal hippocampus, cortex and cerebellum revealed different rates of oxygen consumption, but similar respiratory controls. Oxygen consumption in basal state 4 significantly increased in the mitochondria from all three brain regions from diabetic rats. No relevant differences were observed in the activity of respiratory complexes, but hippocampal mitochondrial membrane potential was reduced. However, ATP content, mitochondrial cytochrome c, and protein levels of β-tubulin III, synaptophysin, and glutamine synthase were similar in brain regions from normal and diabetic rats. In addition, no differences in total glutathione levels were observed between normal and diabetic rat brain regions. Our results indicated that different regions of the brain have specific metabolic responses. The changes in mitochondrial activity we observed at early diabetes induction did not appear to cause metabolic alterations, but they might appear at later stages. Longer-term streptozotocin treatment studies must be done to elucidate the impact of hyperglycemia in brain metabolism and the function of specific brain regions.

Shared and distinct lipid-lipid interactions in plasma and affected tissues in a diabetic mouse model

Lipids are ubiquitous metabolites with diverse functions; abnormalities in lipid metabolism appear to be related to complications from multiple diseases, including type 2 diabetes. Through technological advances, the entire lipidome has been characterized and researchers now need computational approaches to better understand lipid network perturbations in different diseases. Using a mouse model of type 2 diabetes with microvascular complications, we examined lipid levels in plasma and in renal, neural, and retinal tissues to identify shared and distinct lipid abnormalities. We used correlation analysis to construct interaction networks in each tissue, to associate changes in lipids with changes in enzymes of lipid metabolism, and to identify overlap of coregulated lipid subclasses between plasma and each tissue to define subclasses of plasma lipids to use as surrogates of tissue lipid metabolism. Lipid metabolism alterations were mostly tissue specific in the kidney, nerve, and retina; no lipid changes correlated between the plasma and all three tissue types. However, alterations in diacylglycerol and in lipids containing arachidonic acid, an inflammatory mediator, were shared among the tissue types, and the highly saturated cholesterol esters were similarly coregulated between plasma and each tissue type in the diabetic mouse. Our results identified several patterns of altered lipid metabolism that may help to identify pathogenic alterations in different tissues and could be used as biomarkers in future research into diabetic microvascular tissue damage.

In vivo nanotoxicological profile of graphene oxide

Graphene oxide, a widely studied nano materials, exhibits numerous beneficial effects in medical devices. The graphene sample Graphene oxide (GO):Single-layer graphene oxide, purity 99%, thickness 0.7-1.2 nm (AFM); ~300-800nm X&Y dimensions is the standard size <450 nm & 1-20 µm lateral dimensions from Cheap Tubes Inc., Bratleboro, USA was selected for this study. Characterization of GO and stability were previously studied. All the assays were carried out at a concentration of 1 mg/mL (stock suspension by ultrasonication)(stable 10 days). In this study the first parameter evaluated was in animal toxicity in acute and chronic responses. The second one was to observe the morphology and histological changes on major organs, like signs of inflammatory areas. A total of 25 rats (Fischer 344) were divide in 5 groups (n = 5 animals): negative control group (NCT); Positive cancer control group (PCCT); GO group-1 (GO 1); GO group-2 (GO 2) and GO group-3 (GO 3), with different concentrations of graphene oxide. All the groups were treated by via intra peritoneal (i.p) administration. Biochemical and histopathology results of acute toxicity showed no alterations. In the chronic toxicity was found deposit sections and morphology alterations in different tissues (inflammations). Genotoxicity was dose dependent of GO. This study gave us the limit concentrations of GO free for any biological study.

Molecular Analysis and Histopathological Alterations During the Evolution of Trypanosoma evansi Infection in Experimentally Infected Mice Original

The aim of the current study is to follow up Trypanosoma evansi infection in experimentally infected mice by the parasitological and molecular assays. Also, the pathological alterations in different tissues associated with the infection throughout the course of disease were investigated. Forty two male and forty two female Swiss mice were injected I/P by 102 trypanosomes and five mice for each group were kept as non infected control. The course of infection was followed up by direct microscopic examination and PCR assay for T. evansi RoTat 1.2 VSG gene. Pathological changes were also estimated through the disease progression by examination of thin sections from formalin fixed tissues and staining with haematoxylin and eosin. Results revealed earlier detection of T. evansi in mice blood by PCR at 24 h post-infection while direct microscopic examination revealed that the pre-patent period was five days. During the chronic course of the disease, when the parasite disappeared from the blood by direct microscopic examination, PCR assay gave positive signals for the parasitic DNA in the blood. Histopathological examination revealed that T. evansi induced destructive irreversible damage of the mice vital organs (kidneys, liver, spleen, brain and testes) especially in chronic infection and lead to death of the animals with progression of the disease. It also affects animals’ fertility. It induces degenerative changes in the testes and seminiferous tubules.

Effect of Fractionated Doses of Cerastes Cerastes Crude Venom on Tissues of Irradiated Mice

) crude venom (CCV) on physiological alterations in different tissues of 5.5 Gy γ-irradiated mice. Male mice were grouped into: Control group. CCV group; mice received via inter peritoneum (i.p.) ⅓LD50 CCV in fractionated doses over a period of 2 weeks. Irradiated group; mice whole body exposed to 5.5 Gy γ-rays. Irradiated+ CCV; mice received via i.p ⅓LD50 CCV in fractionated doses over a period of 2 weeks starting 1 h post irradiation. Exposure to 5.5 Gy γ-rays elevated advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content of liver, spleen and kidney. Moreover, γ-irradiation significantly decreased calcium (Ca) and elevated zinc (Zn), and cupper (Cu) in liver, spleen and kidney tissues compared to the control, whereas, iron (Fe) was significantly elevated in liver and spleen and decreased in kidney. In addition, serum urea and creatinine and their ratio were significantly increased. Irradiated mice treated with fractionated CCV showed significant amelioration of oxidative stress and element alterations in the different tissues. It could be concluded that the fractionated doses of CCV (⅓LD50) might have favourable potential against irradiation induced-biochemical injuries.

Long Term Expression of Drosophila melanogaster Nucleoside Kinase in Thymidine Kinase 2-deficient Mice with No Lethal Effects Caused by Nucleotide Pool Imbalances

Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2(-/-)) mice extended the life span of Tk2(-/-) mice from 3 weeks to at least 20 months. The Dm-dNK(+/-)Tk2(-/-) mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK(+/-)Tk2(-/-) mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK(+/-) mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues.

Toxicity of sodium fluoride (NaF) to juvenile catfish, Clarias batrachus

Effects of sodium fluoride (NaF) on Clarias batrachus in the aquarium at a sub lethal dose of 0, 15, 30, 40, 50 and 60 mg/l for a chronic exposure period of 120 days were evaluated. The histopathological alterations in different tissues from brain, gill and liver were examined in fishes showed abnormal behaviors. Such as rupture of hepatocytes, congestion, necrosis pyknosis, cellular infiltration, and degenerative changes. In case of liver, individualization of hepetocytes, mild necrosis, vacuolation, pyknosis and hemorrhage were observed. These results suggest that NaF affects severely on the tissues of the internal organs leading to threat of life and survival.&#x0D; Dhaka Univ. J. Biol. Sci. 22(1): 1-7, 2013 (January)

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.