scholarly journals Analysis of toxicity of iron oxide nanocomposite encapsulated in a polymer matrix of arabinogalactan

2021 ◽  
Vol 100 (3) ◽  
pp. 285-289
Author(s):  
Eugeny A. Titov ◽  
Larisa M. Sosedova ◽  
Mkhail A. Novikov

Introduction. The article presents a toxicity analysis of the Fe3O4 nanocomposite encapsulated in the natural polymer matrix of arabinogalactan (AG). A study was devoted to forming and developing the biological response of organisms to subacute administration of this nanocomposite. Materials and methods. White outbred male rats weighing 200-220 gr. were used in this study. For ten days, a test drug solution was administered orally to animals with a probe at a dose of 500 μg of iron per kilogram of body weight. Then, using histological and immunohistochemical analysis methods, the severity of the biological response of the organism to the introduction of this nanocomposite was evaluated. An analysis was made of the state of tissue of the liver, kidneys, and sensorimotor cortex. The number of neurons with the proapoptotic caspase three protein expression, anti-apoptotic bcl-2 protein, and HSP 70 stress protein was determined in the sensorimotor cortex tissue. Results. With intragastric administration to experimental animals, there was a violation of normal blood rheology in liver and kidney tissue, protein dystrophy of hepatocytes, expansion of perivascular spaces of brain tissue, and a decrease in the total number of sensorimotor cortex neurons per unit area. Immunohistochemical analysis of tissue of the sensorimotor cortex for expression of pro-and anti-apoptotic proteins and the expression of HSP 70 protein showed a sharp increase in the number of neurons with the expression of HSP 70 stress protein. Discussion. The nature of the detected changes indicates the occurrence of compensatory-adaptive reactions in the organism in response to the effect of FeAG. The lack of expression of caspase 3 protein eliminates the development of apoptosis.

2021 ◽  
Vol 6 (5) ◽  
pp. 92-99
Author(s):  
E. A. Titov ◽  
V. S. Rukavishnikov ◽  
L. M. Sosedova ◽  
M. A. Novikov ◽  
E. V. Buynova

Introduction. Due to their high biocompatibility, substances based on nanosized selenium particles, encapsulated in natural or synthetic polymer matrices, are promising materials for the creation of biomedical preparations of diagnostic and therapeutic value. Selenium nanoparticles are successfully used in the diagnosis of various types of cancer. In addition to the diagnostic value, selenium nanoparticles have their own prophylactic and oncological effect. This paper presents the results of a study of the toxicity of the Se nanocomposite encapsulated in the polymer matrix of arabinogalactan (SeAG). The emergence and development of the pathological process in the tissue of the brain, liver and kidneys during subacute administration of this nanocomposite was studied.Materials and methods. Twenty white outbred male rats weighing 200–220 g were used in the work. Animals were orally administered a solution of the selenium nanocomposite at a dose of 500 μg per kilogram of animal body weight for 10 days. Then, using the methods of histological analysis, the severity of the biological response of the organism to the introduction of this nanocomposite was assessed. An analysis of the state of the tissue of the liver, kidneys and the sensorimotor cortex of the brain was carried out.Results. With the intragastric administration of this drug, there is stasis of blood in the portal tracts, a pronounced macrophage reaction and diapedesis of leukocytes in the liver tissue. There is a decrease in the number of normal neurons per unit area, a decrease in the number of astroglia cells and an increase in the number of  degeneratively altered neurons in the tissue of the sensorimotor cortex. There is also an increase in connective tissue in the cortex of the kidney, with the formation of fibrosis and a decrease in the area of the Shumlyansky – Bowman capsule.Conclusion. The effect of the investigated nanocomposite is characterized by the development of a pronounced pathological process in the central nervous and hepatorenal systems of the body. 


2017 ◽  
Vol 21 (1) ◽  
pp. 57-67
Author(s):  
S. I. Dolomatov ◽  
V. G. Sipovski ◽  
N. Y. Novikov ◽  
I. N. Kasich ◽  
I. V. Myshko ◽  
...  

THE AIM: to study of the dynamics of structural changes in renal parenchyma of rats exposed to long-term combined effects of thyroxine and propylthiouracilum (PTU). MATHERIAL AND METHODS – studies were performed on mongrel white male rats weighing 250-300g. Hyperthyroidism was caused by daily intragastric administration of thyroxine (T4) in amount of 50g per 100g of body weight over 30 days. On the first day of the experiment animals were divided into 2 groups. Animals of the first group (n = 25) received only T4. The rats of the second group (n = 25) were administrated propylthiouracilum and T4 daily. PTU was administered intragastric in amount of 1 mg per 100g of body weight. Kidney tissue samples were collected on the 10th, 20th and 30th days of the experiment. In addition, there were collected kidney tissue samples of the animals treated with only T4 after 20 days after cessation of hormone. Obtained tissue samples were fixed and treated by the usual method, followed by filling in paraffin. Sections were stained with hematoxylin and eosin. RESULTS – it was established that course of experimental hyperthyroidism leads to significant structural abnormalities of the renal parenchyma. Leading features of kidneys pathology at a hyperthyroidism are rough structural damages of the nephron tubular epithelium. CONCLUSIONS – combined administration in rats of thyroxin and propylthiouracilum has weakly expressed beneficial effect by limiting the development of structural damages to the renal parenchyma and clot formation. 


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 784
Author(s):  
Sandra Minic ◽  
Marion Florimond ◽  
Jérémy Sadoine ◽  
Anne Valot-Salengro ◽  
Catherine Chaussain ◽  
...  

Dental pulp is a dynamic tissue able to heal after injury under moderate inflammatory conditions. Our study aimed to evaluate pulp repair under inflammatory conditions in rats. For this purpose, we developed a rat model of controlled pulpitis followed by pulpotomy with a tricalcium silicate-based cement. Fifty-four cavities were prepared on the occlusal face of the maxillary upper first molar of 27 eight-week-old male rats. E. coli lipopolysaccharides at 10 mg/mL or phosphate-buffered saline PBS was injected after pulp injury. Non-inflamed molars were used as controls. Levels of inflammation-related molecules were measured 6 and 24 h after induction by enzyme-linked immunosorbent assay of coronal pulp samples. Pulp capping and coronal obturation after pulpotomy were performed with tricalcium silicate-based cement. Four and fifteen days after pulpotomy, histological and immunohistochemical analysis was performed to assess pulp inflammation and repair processes. Our results showed significantly higher levels of innate inflammatory proteins (IL-1β, IL-6, TNF-α and CXCL-1) compared with those in controls. Moderate residual inflammation near the capping material was demonstrated by histology and immunohistochemistry, with the presence of few CD68-positive cells. We showed that, in this model of controlled pulpitis, pulpotomy with BiodentineTM allowed the synthesis at the injury site of a mineralized bridge formed from mineralized tissue secreted by cells displaying odontoblastic characteristics. Analysis of these data suggests overall that, with the limitations inherent to findings in animal models, pulpotomy with a silicate-based cement is a good treatment for controlling inflammation and enhancing repair in cases of controlled pulpitis.


2011 ◽  
Vol 1 (1) ◽  
pp. 9
Author(s):  
Ipseeta Ray Mohanty ◽  
Ujjwala Maheswari ◽  
Daniel Joseph ◽  
Yeshwant Deshmukh

The present study was undertaken to evaluate the cardioprotective activity of Tribulus terrestris (Tt), a medicinal herb following isoproterenol (ISP)-induced myocardial injury. The contribution of heat shock protein (HSP) 70, key anti-stress protein, endogenous antioxidants and oxidant -antioxidant balance in attenuating myocardial injury was further studied. Hydroalcoholic extract of Tt {1, 2.5, 5 & 10 mg/kg} were orally fed once a daily to Wistar rats for 21 days. On the 20th and 21st day, both control (ISP control) and Tt fed rats were challenged with ISP (85 mg/ kg, s. c. two doses at 24h intervals) induced myocardial necrosis. Histopathological evaluation, cardiac marker enzyme: Creatinine phospho - kinase(CPK) and antioxidative parameters: Glutathione (GSH), Thiobarbituric acid reactive substances (TBARS), Catalase (CAT), Glutathione peroxidase (GSHPx) and Superoxide dismutase (SOD) levels were estimated. Tt (2.5 mg/kg) intake per se upregulated HSP 70; increased basal SOD, CAT activity (P<0.05) and caused a marked fall in basal TBARS levels (P<0.05) in comparison to sham. Following ISP challenge, significant oxidative stress with evidence of myocardial necrosis was observed in the ISP control group. ISPinduced changes in myocardial SOD, GSHPx and GSH were prevented by both the 2.5 and 10 mg/kg doses of Tt, though cellular injury was minimal with 2.5 mg/kg dose. The results emphasize that pre-treatment with Tt offered significant protection against ISP-induced myocardial necrosis through a unique property of enhancement of endogenous antioxidants, stabilization of cytoskeleton structure which in turn is attributed to HSP 70 expression along with fortified antioxidant defense system.


1995 ◽  
Vol 309 (2) ◽  
pp. 453-459 ◽  
Author(s):  
L Tacchini ◽  
G Pogliaghi ◽  
L Radice ◽  
E Anzon ◽  
A Bernelli-Zazzera

Post-ischaemic reperfusion increases the level of the major heat-shock (stress) protein hsp 70 and of its mRNA by transcriptional mechanisms, and activates the binding of the heat-shock factor HSF to the consensus sequence HSE. In common with CoCl2 treatment, post-ischaemic reperfusion increases the level of haem oxygenase mRNA, an indicator of oxidative stress, but CoCl2 does not seem to induce the expression of the hsp 70 gene [Tacchini, Schiaffonati, Pappalardo, Gatti and Bernelli-Zazzera (1993) Lab. Invest. 68, 465-471]. Starting from these observations, we have now studied the expression of two genes of the hsp 70 family and of other possibly related genes under conditions of oxidative stress. Three different chemicals, which cause oxidative stress by various mechanisms and induce haem oxygenase, enhance the expression of the cognate hsc 73 gene, but do not activate the inducible hsp 70 gene. Expression of the other genes that have been studied seems to vary in intensity and/or time course, in relation to the particular mechanism of action of any single agent. The pattern of induction of the early-immediate response genes c-fos and c-jun observed during oxidative stress differs from that found in post-ischaemic reperfused livers. Oxidative-stress-inducing agents do not promote the binding of HSF to its consensus sequence HSE, such as occurs in heat-shock and post-ischaemic reperfusion, and fail to activate AP-1 (activator protein 1). With the possible exception of Phorone, the oxidative stress chemically induced in rat liver activates NFkB (nuclear factor kB) and AP-2 (activator protein 2) transcription factors.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad-Sedigh Khosravi ◽  
Alireza Samimiat ◽  
Bahar Mazaheri ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
...  

Backgrounds. Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods. Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results. Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly ( P < 0.05 ) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% ( P < 0.05 ). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion. Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.


2008 ◽  
Vol 60 (4) ◽  
pp. 581-591
Author(s):  
Sanja Dacic ◽  
Sanja Pekovic ◽  
Maja Stojiljkovic ◽  
Irena Lavrnja ◽  
Danijela Stojkov ◽  
...  

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.


2018 ◽  
Vol 37 (4) ◽  
pp. 285-295 ◽  
Author(s):  
Gabriel A. Dedeke ◽  
Folarin O. Owagboriaye ◽  
Kehinde O. Ademolu ◽  
Olanrewaju O. Olujimi ◽  
Adeyinka A. Aladesida

There have been major concerns that the nephrotoxicity of commercial formulations of Roundup herbicide is due to the active ingredient glyphosate. We therefore investigated and compared the mechanisms underlining the nephrotoxicity of Roundup herbicide and glyphosate alone in rat. Fifty-six adult male rats randomized into 7 groups of 8 rats per group were exposed to Roundup formulation and glyphosate alone daily by gavage at 3.6, 50.4, and 248.4 mg/kg body weight (bw) of glyphosate concentrations for 12 weeks with distilled water administered to the control group. Kidney biomarker (serum urea and creatinine, plasma cystatin-C, and neutrophil gelatinase-associated lipocalin), oxidative stress indices in the kidney tissue, activities of kidney membrane-bound enzymes (Mg-adenosine triphosphatase [ATPase], Ca-ATPase, Na/K-ATPase, and total ATPase), and histopathological changes in the kidney were monitored. Glyphosate concentration in the kidney was quantified by high-performance liquid chromatography with ultraviolet detection. Significant ( P < 0.05) alterations in the levels of the kidney biomarker, oxidative stress markers, and membrane-bound enzymes were observed in the rats exposed to Roundup compared to the rats exposed to glyphosate alone. Rats exposed to Roundup accumulated more glyphosate residue in their kidney tissue. Severe histopathological lesions were only seen in the kidneys of rats exposed to Roundup. The nephrotoxicity observed cannot be due to the active ingredient in the Roundup formulation, as glyphosate alone has virtually no effect on the renal function of the exposed animals. Therefore, the general claim attributing nephrotoxicity of a glyphosate-based herbicide to its active ingredient should be discouraged.


2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable


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