Brain Of Albino Rats Research Articles

Evaluating the possible genotoxicity of nanoaluminum incorporated in human vaccines and the potential protective role of nanocurcumin: an in vivo study

For nearly 90 years, aluminum (Al) salts have been utilized as vaccination adjuvants. Nevertheless, there is a risk of adverse effects associated with the amount of nanoaluminum used in various national pediatric immunization regimens. This study aimed to investigate the possible genotoxic effects of nanoaluminum incorporated in human vaccines on the brains of newborn albino rats and whether nanocurcumin has a potential protective effect against this toxicity. Fifty newborn albino rats were randomly assigned to 5 groups, with 10 in each group. Groups 1 and 2 received "high" and "low" Al injections corresponding to either the American or Scandinavian pediatric immunization schedules, respectively, as opposed to the control rats (group 5) that received saline injections. Groups 3 and 4 received the same regimens as groups 1 and 2 in addition to oral nanocurcumin. The expression of both the cell breakdown gene tumor protein (P53) and the cell stress gene uncoupling protein 2 (UCP2) was significantly greater in groups 1 and 2 than in group 5. Groups 1 and 2 exhibited severe DNA fragmentation, which was observed as DNA laddering. Nanocurcumin significantly reduced the expression of the P53 and UCP2 genes in groups 3 and 4, with very low or undetectable DNA laddering in both groups. Vaccination with nanoaluminum adjuvants can cause genotoxic effects, which can be mediated by the inflammatory response and oxidative stress, and nanocurcumin can protect against these toxic effects through the modulation of oxidative stress regulators and gene expression.

Neuroprotective Assessment of Betaine against Copper Oxide Nanoparticle-Induced Neurotoxicity in the Brains of Albino Rats: A Histopathological, Neurochemical, and Molecular Investigation.

Copper oxide nanoparticles (CuO-NPs) are commonly used metal oxides. Betaine possesses antioxidant and neuroprotective activities. The current study aimed to investigate the neurotoxic effect of CuO-NPs on rats and the capability of betaine to mitigate neurotoxicity. Forty rats; 4 groups: group I a control, group II intraperitoneally CuO-NPs (0.5 mg/kg/day), group III orally betaine (250 mg/kg/day) and CuO-NPs, group IV orally betaine for 28 days. Rats were subjected to neurobehavioral assessments. Brain samples were processed for biochemical, molecular, histopathological, and immunohistochemical analyses. Behavioral performance of betaine demonstrated increasing locomotion and cognitive abilities. Group II exhibited significantly elevated malondialdehyde (MDA), overexpression of interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). Significant decrease in glutathione (GSH), and downregulation of acetylcholine esterase (AChE), nuclear factor erythroid 2-like protein 2 (Nrf-2), and superoxide dismutase (SOD). Histopathological alterations; neuronal degeneration, pericellular spaces, and neuropillar vacuolation. Immunohistochemically, an intense immunoreactivity is observed against IL-1β and glial fibrillary acidic protein (GFAP). Betaine partially neuroprotected against CuO-NPs associated alterations. A significant decrease at MDA, downregulation of IL-1β, and TNF-α, a significant increase at GSH, and upregulation of AChE, Nrf-2, and SOD. Histopathological alterations partially ameliorated. Immunohistochemical intensity of IL-1β and GFAP reduced. It is concluded that betaine neuroprotected against most of CuO-NP neurotoxic effects through antioxidant and cell redox system stimulating efficacy.

Ameliorative Effect of Taurine on Nandrolone Decanoate Induced Toxicity on Brain, Heart and Testis in Adult Male Albino Rats

Ameliorative Effect of Taurine on Nandrolone Decanoate Induced Toxicity on Brain, Heart and Testis in Adult Male Albino Rats

Hesperidin Attenuates Titanium Dioxide Nanoparticle-Induced Neurotoxicity in Rats by Regulating Nrf-2/TNF-α Signaling Pathway, the Suppression of Oxidative Stress, and Inflammation.

Background: Titanium dioxide nanoparticles (TiO2NPs) are widely utilized and consumed mainly as food additives. Oxidative stress is considered to be the basic effect of TiO2NPs through biological interactions. Hesperidin (HSP) is a bioflavonoid (flavanone glycoside) with lipid-lowering, inflammation, oxidative stress suppression, antihypertensive, cancer-fighting, and antiedema effects. Objective: This study was to investigate the possible protective influences of HSP of subchronic oral TiO2NP exposure on the brains of rats, including neurotransmitters, oxidative stress/antioxidant parameters, inflammatory markers, and histological changes in the brains of adult male albino rats. Methodology: The experiment was executed on 80 albino rats. The animals were randomly divided into 4 equal groups. The first group served as a control; the second group was treated with oral doses of HSP (100 mg/kg Bw daily); the third group received TiO2NPs (200 mg/kg Bw orally daily); and the fourth group was treated with TiO2NPs and an oral dose of HSP daily for 8 weeks. Blood samples were obtained for biochemical analysis. Neurotransmitters, oxidative stress biomarker levels, and inflammatory markers were measured in brain homogenates. Histological examination of the brain was performed through H&E staining. Results: Coadministration of hesperidin with TiO2NPs orally for 8 weeks decreased the levels of MDA, TNF-α, AChE, and dopamine in brain homogenates, which were increased in the TiO2NP group. It increased the other oxidative biomarkers (SOD, CAT, and GPx) and Nrf-2 expression levels. Brain histological sections of the TiO2NP-treated group show degeneration, necrosis, congestion, and inflammatory cell infiltration that decreased markedly in the coadministration of hesperidin with the TiO2NP group. Conclusion: Hesperidin cotreatment offers significant protection against TiO2NP-induced oxidative stress and biochemical and histological alteration in the brain.

The histostereological teratogenic effects of in-utero exposure to varied doses of lamotrigine on the developing fetal brain in albino rats (Rattus Norvegicus)

The histoqualitative teratogenic effects of lamotrigine, a second-line anticonvulsant medicine, on the developing fetal brain structures when exposed in utero in a time- and dose-dependent manner remain unclear. On the other hand, lamotrigine is currently being widely prescribed as a first-line medicine in the management of maternal conditions like epileptic seizures and bipolar disorders, among others. The preferential use of lamotrigine is attributed to the considerations of its efficacy, tolerability, and minimal teratogenic effects on fetal organs like the brain, among others, though with insufficient supportive data. The aim of this study was therefore to evaluate the histo-quantitative effects of lamotrigine on the developing fetal brain structures when exposed in utero at varying dosages during different trimesters. The study adopted a post-test only experimental study design where a sample size of 30 sexually mature albino rat dams of the species (Rattus norvegicus) weighing between 250 + 30 grams was used. The rats were divided into two broad groups: 3 control rats and 27 dosage rats. The data collected was coded in Excel spreadsheets and analyzed in SPSS. Results were expressed as the mean + standard error of the mean (SEM), and values with a P < 0.05 were considered to be significant. Study findings depicted a reduction in brain weights, length, width, volumes, and volume densities of cortical and subcortical layers in a dose- and time-dependent manner. High lamotrigine dosages, especially during the first and second trimesters, were observed to be associated with significant mean reductions in the brain weights, length, width, volumes, and volume densities of the developing fetal brain structures. Therefore, further studies with higher primates closer to the human species as well as clinical trials are recommended to rule out the safety index of lamotrigine during pregnancy.

GABA Administration Ameliorates the Toxicity of Doxorubicin on CSF and the Brain of Albino Rats.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain and is a non-proteinogenic amino acid. Doxorubcin (DOX) or adriamycin is one of the most potent chemotherapy drugs for breast cancer. This study focused on diminishing the brain injury and neurotoxicity of doxorubicin (DOX) by GABA administration. Rats were randomly divided into four groups (8 rats each), which were the control group, DOX group (3 mg/kg for 4 weeks, then 2 mg/kg for 2 weeks), GABA group (2 mg/kg for 21 days), and DOX + GABA group (treated as the second and third groups). Neurotoxicity and brain injury were assessed by determining CSF biomarkers, serum inflammatory markers, and histopathological evaluation of the cerebral cortex. DOX treatment significantly increased the levels of all CSF biomarkers (S100B, IL-1β, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), spectrin breakdown products (SBDP145), and C-C motif chemokine ligand 2 (CCL2) and all inflammatory markers (IL-6, TNF-α, and IFN-γ), causing extensive neutrophilic infiltration and great alteration in the cerebral cortex architecture as evidence of neurotoxicity. The oral administration of GABA significantly reduced the levels of all CSF biomarkers and inflammatory markers and restored the normal architecture of the cerebral cortex, with observed ameliorations in neutrophilic infiltration. GABA administration can ameliorate neurotoxicity and protect the brain against the negative effects of DOX treatment.

Coenzyme Q10 treatment and diazinon exposure in parental male rats: effects of the exposure on their neonatal brains.

Prenatal acute and chronic exposure to organophosphorus pesticides may evoke physical and behavioral impairments in offspring development. However, the mechanism of antioxidant consumption repair to cure these impairments remains unclear. This study aimed to investigate the protective effects of COQ10 against DZN toxicity by measuring Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, the expression of MH2A, DNMT1, H2AZ, and HDAC3, and the histopathology in the brain of neonatal Wistar albino rats whose male parents were exposed to DZN and COQ10. The results showed that COQ10 could significantly decrease MDA level, histopathological alteration, and expression of DNMT1 and HDAC3 in the neonatal brain (P<0.05). Also, an increase in SOD activity and expression of MH2A and H2AZ were observed in the neonatal brain of this group (P<0.05). These investigations suggest that COQ10 can reduce the effects of DZN on neuronal oxidative stress and its damage to the neonatal brain.

Cytotoxicity associated with acute and chronic administration of synthetic cannabinoids “Strox” in the brain, liver, heart, and testes of male albino rats: histological and immunohistochemical study

BackgroundSynthetic cannabinoids are one of the largest groups of new psychoactive substances that invaded Egypt’s drug abuse market over the past few years.AimRandomized controlled trial study to demonstrate the effects of acute and chronic toxicity by synthetic cannabinoid (Strox) on the brain, liver, heart, and testes in adult male albino rats through histopathological examination by light microscope and immunohistochemistry.MethodsTotal number of fifty male albino rats were divided into five different groups, two control and three treated groups. Negative and positive control groups received distilled water and dimethyl sulfoxide, respectively, acute group received LD50 (lethal dose 50) once and observed for 14 days, chronic group received 1/10 LD50 for 3 months, and finally chronic withdrawal groups received 1/10 LD50 for 3 months and then left 2 weeks without the substance to observe the withdrawal manifestations.ResultsThe current study revealed various histopathological changes in all organs with increased expression of cannabinoid receptor 1. The most important findings observed by light microscope examination were shrinkage and degenerative changes in Purkinje cells in brain sections, abnormalities in blood sinusoids and architecture in liver section, disruption in cardiac muscle fiber in heart sections, and finally testes showed irregularities in seminiferous tubules and germinal cells. Immunohistochemical staining for caspase-3 in the brain, liver, and heart showed weak-positive reaction in acute group and a strong reaction with chronic groups. Additionally, increase in collagen fiber was observed in sections of the liver and heart of chronic group.ConclusionsSynthetic cannabinoid sample (Strox) toxicity caused adverse effects on the brain, liver, heart, and testes as shown by increasing cannabinoid receptor 1 and caspase-3 expression.

The effects of hydrogen cyanamide (dormex) on the brain and lungs of albino rats and the potential protective impact of vitamin E

The effects of hydrogen cyanamide (dormex) on the brain and lungs of albino rats and the potential protective impact of vitamin E

Chronic atrazine exposure increases the expression of genes associated with GABAergic and glutamatergic systems in the brain of male albino rat.

The herbicide atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is widely used to destroy grasses and broadleaf weeds in crops and some fruits. Studies in rodents have shown that acute, repeated or chronic exposure to ATR is associated with alterations in the nigrostriatal dopaminergic pathway, whereas its effects on GABAergic and glutamatergic pathways have only recently been reported. Sprague-Dawley male rats were exposed daily to 1 or 10 mg ATR/kg of BW for 13 months to evaluate the ATR effects on GABAergic and glutamatergic systems. At the end of the ATR treatment, the levels of mRNA of several genes involved in the production, vesiculation, reuptake, and receptors of GABA and Glu in the striatum (STR), nucleus accumbens (NAcc), prefrontal cortex (PFC), ventral midbrain (vMID) and hippocampus (HIPP) were evaluated by absolute qPCR. For the GABAergic genes, increased expression of GAD67 and Slc32a1 in STR and/or vMID in rats exposed to 1 and/or 10 mg ATR were detected. With regard to the expression of genes involved in the glutamatergic system, Slc17a6 and Grin1 in HIPP of rats exposed to 1 and/or 10 mg ATR, increased as was Gria1 in STR and PFC in the group exposed to 1 mg ATR. In the same fashion, Slc1a3 expression and MGLUR1 increased in STR of rats exposed to 1 and 10 mg ATR groups. The expression of the glutaminases gls (variants 1 and 2) was greater in STR, NAcc, HIPP, and PFC of rats exposed to 1 and/or 10 mg ATR. These findings show that the GABAergic and, especially glutamatergic systems are targets of ATR exposure.

Potential Protective Role of Curcumin on the Toxic Effect of Food Azo Dye Tartrazine on the Brain of Young Albino Rats

The use of coloring agents in food industry has dramatically increased. Children are the main consumers of colored food products and beverages and are more vulnerable to the effects of synthetic colorants. Curcumin, an active constituent of turmeric plant, has been the subject of extensive studies assessing its antioxidant properties. The present study was conducted to evaluate the protective potentials of curcumin against neurotoxicity induced by the synthetic food colorant; tartrazine. Thirty-six young male albino rats were divided into six groups; negative control (Group I), distilled water (Group II), corn oil (Group III), curcumin (Group IV), tartrazine (Group V) and tartrazine+curcumin (Group VI). At the end of the study, the rats were subjected to biochemical, histological and immunohistochemical staining for GFAP. Our results showed that tartrazine induced a significant decrease in GSH, serotonin and GABA levels and a significant increase in MDA levels in the brain as compared to control groups. Tartrazine induced apoptosis, vacuolations, congestion and cellular infiltration in the brain tissue. An immunohistochemistry study showed astrogliosis with increased expression of GFAP. Curcumin ameliorated all these effects. In conclusion, tartrazine is neurotoxic. Increased brain oxidative stress and cellular damage are contributing factors. Curcumin can prevent tartrazine-induced neurotoxicity.

Analysis of Histological Features of the Cerebral Cortex and Hippocampus of Albino Rats Using Haematoxylin &amp; Eosin Stain- An Observational Study

Background: The study determined the histological layers of the cerebral cortex and hippocampus of the albino rat brain samples has been used in the study. The Cerebral cortex is composed of the Molecular layer, external granular, external pyramidal layer, internal granular layer and interior pyramidal layer. The layers of the hippocampus are alveus, stratum oriens, stratum pyramidale, stratum radiatum, stratum lacunosum and stratum moleculare. The aim of the study is to analyze the detailed histological features of the cerebral cortex and hippocampus layers of albino rats at the magnification of 10X,100X,40X. By using haematoxylin and eosin stain as an observational study.&#x0D; Materials and Methods: The samples were preserved and fixed with the formalin and stained by haematoxylin and eosin and observed with a light microscope.&#x0D; Results: The molecular layer is the superficial layer containing neurons. The outer granular layer of the cells are densely packed. Outer pyramidal layer contains rich pyramidal cells, Inner granular layer contains stellate cells, Inner pyramidal layer contains glial cells and the deeper multiform layer is composed of pyramidal cells. The hippocampus contains three layers of cornu Ammonia CA1, CA2, CA3. CA1 responds to memory and is covered by the choroid plexus. CA2 contains 3 major cell dentate gyrus, pyramidal cells, pyramidal neurons and CA3 composed of stratum lucidum.&#x0D; Conclusion: The study of brain analysis of histological features of the cerebral cortex and hippocampus of the brain adds a greater insight in understanding the histology of various types of layers in rat brain and morphology of brain cells.

Arsenic trioxide induced toxicity and assimilation assessment in vital organs of Rattus norvegicus

Arsenic is available in environment due to anthropogenic and natural activities. Arsenic trioxide is considered as neurotoxic, hepatotoxic, nephrotoxic, hemtoxic and carcinogenic. In present study Arsenic trioxide (As2O3) has been used as test chemical to evaluate its toxic potential in vital organs like brain, liver and kidney of male albino rat. 61 mature male Albino rats were used in present study. 36 were used for control, acute and sub-acute groups excluding 25 rats for the calculation of median lethal dose. Control group was unexposed to Arsenic trioxide whereas acute group includes 3 hrs, 6 hrs, 12 hrs and 1 day duration of exposure to As2O3. Likewise sub-acute group includes 7, 14, & 21 days treatment to Arsenic trioxide. Rats of acute and sub-acute groups were supplemented with As2O3 orally in mg/Kg body weight accordingly. Accumulation of Arsenic trioxide was higher in liver followed by kidney and brain. The aim of study is to extrapolate existing findings of retention potential of arsenic in vital organs and peripheral blood and consequently helpful in assessing the toxicity and hazardous effects of test chemical.

Neuroprotective Potentials of Cocculus hirsutus Leaf Extract Against 6,7-Epoxytropine Tropate-Induced Memory Impairment in Rats

Cocculus hirsutus, a tropical South Asian creeper,traditionally used as a diuretic, laxative, cardiotonic, anti-microbial, antidiabetic, anti-inflammatory and spermatogenic. However, the neuroprotective role was less explored; therefore, this researchwas conducted to investigate neuroprotective potentials of Cocculus hirsutus leaf hydroalcoholic extract in 6,7-Epoxytropine tropate (Scopolamine) induced cognitive impairment and oxidative lipid peroxidation in the brain of wistar albino rat. Scopolamine (1 mg/kg body weight, i.p.) was given in rats for 14 days to induce transient cognitive impairment. Donepezil (2 mg/kg body weight, orally) has been used for this research as a positive control. Behavioral studies were done using Morris water maze and elevated plus maze and neurobiochemical parameters such as acetylcholinesterase activity, reduced glutathione levels and activity of catalase were assessed in rats brain homogenate. Cocculus hirsutus leaf hydroalcoholic extract(200 mg/kg and 400 mg/kg) exhibited an improvement in spatial, exteroceptive learning and memory. The extract showed significant decline in the activity of acetylcholinesterase, enhancement of reduced glutathione levels and catalase activity (p&lt;0.001). All the outcomes were assessed by Bonferroni post hoc tests with ANOVA for multiple comparison studies. This study reveals that hydroalcoholic extract of Cocculus hirsutusleaf acts as neuroprotective against scopolamine induced behavioral and neurobiochemical changes.

Apoptosis is induced by sub-acute exposure to 3-MCPD and glycidol on Wistar Albino rat brain cells

3-chloropropane-1,2-diol (3-MCPD) and its toxic metabolite glycidol were classified by the International Agency for Research on Cancer (IARC) as belonging to group 2B and 2A for humans. This study aimed to determine the sub-acute toxicity of these agents. Rats were exposed to 3-MCPD at 0.87 and 10 mg/kg/bw and glycidol (2,4 and 37,5 mg/kg/bw) for 90 days. miR-21 gene expression levels significantly decreased in all group’s cerebellar tissues compared with control. Exposure to 10 mg/kg/bw 3-MCPD showed significant increases in PTEN in brain as compared to control group. The Akt gen expressions were significantly decreased in 3-MCPD and glycidol groups when compared to control group brains. Additionally, Caspase 3 and AIF immunopositivity significantly increased in 3-MCPD high dose and glycidol high dose groups in cerebellum granular layers compared to control. The results of the present study conclude that 3-MCPD and glycidol can induce apoptosis in rat brain tissue.

Some Kinetic Features of Na,K-ATPase and Sensitivity to Noradrenaline

A comparative kinetic analysis of albino rat brain synaptic and kidney plasma membrane fraction Na,K-ATPase was performed to comprehend the different levels of sensitivity of these fractions to the neurotransmitter noradrenaline. Noradrenaline (NA) inhibits the rat brain synaptic membrane Na,K-ATPase, changes the stoichiometry of Na+ and K+ and shifts the enzyme system from an MgATP to an Mg2+ dependent cycle. While the kidney plasma membrane fraction Na,K-ATPase is not sensitive to noradrenaline. To investigate the mechanism underlying this difference, we studied enzyme velocity dependence on the concentration of Mg2+. The 1/V = f(Mg2+) function has shown different kinetic features for the synaptic and kidney plasma membrane Na,K-ATPase. With the addition of ethylene glycol tetraacetic acid (EGTA) to the reaction medium the geometric form of 1/V = f(Mg2+) function is affected differently. We thereafter measured the essential activator number for Na+ and K+ with, in excess Mg2+. The results of these experiments reveal that, contrary to the synaptic membrane Na,K-ATPase, the kidney plasma membrane fraction Na,K-ATPase does not possess an Mg2+ dependent cycle and noradrenaline exhibits different modulatory effects on the enzyme system.

Sub-chronic Toxic Effects of Tartrazine on The Heart and Brain of Adult Male Albino Rats and The Protective Effect of Vitamin E

Sub-chronic Toxic Effects of Tartrazine on The Heart and Brain of Adult Male Albino Rats and The Protective Effect of Vitamin E

The ameliorative effect of nanoselenium on histopathological and biochemical alterations induced by melamine toxicity on the brain of adult male albino rats

Melamine is a chemical substance used as a food adulterant because of its high nitrogen content; it is known to induce neurotoxicity, thereby adversely affecting the central nervous system. The biocompatibility, bioavailability, lower toxicity, and the large surface area of nanosized selenium relative to its other forms indicate that selenium nanoparticles (SeNPs) have a potential ameliorative effect against melamine-induced neurotoxicity. In this study, we tested this hypothesis using 40 adult male albino rats that were randomly assigned into four groups (n = 10 per group): group I rats served as the untreated negative controls and were fed with standard diet and distilled water; group II rats were orally treated with melamine (300 mg/kg body weight/d); group III rats orally received melamine (300 mg/kg body weight/d) and SeNPs (2 mg/kg body weight/d); and group IV rats received SeNPs only (2 mg/kg body weight/d) for 28 days. Blood and brain samples were collected from all rats and processed for biochemical, histopathological, and immunohistochemical investigations. SeNPs were encapsulated in starch as a natural stabilizer and a size-controlling agent (SeNP@starch). The prepared SeNPs were characterized using different techniques. Inductively coupled plasma-optical emission spectrometry (ICP-OES) indicated that the percentage of selenium loaded in starch was 1.888 %. Powder x-ray diffractometer (XRD) was used to investigate the crystalline structure of the Se-NP@starch, to be tubular and composed of amorphous starch as well as metallic selenium. Thermogravimetric analysis confirmed the thermal stability of the product and determined the interactions among the different components. Transmission electron microscope demonstrated the spherical shape of SeNPs and their dispersion into starch surface as well as evaluating their size in nanoscale (range 20−140 nm). Our results revealed that the melamine- exposed rats had significantly elevated in malondialdehyde levels, significantly reduced in total antioxidant capacity, down-regulated expression of the antioxidant related genes Nrf2 (nuclear factor erythroid 2–related factor 2) and GPx (glutathione peroxidase), as well as up-regulated expression of the apoptosis-related gene Bax (B-cell lymphoma 2–associated X protein), with down regulation of Bcl-2 (B-cell lymphoma 2). Histopathological examination exhibited several alterations in the cerebrum, cerebellum, and hippocampus of the treated rats compared with the controls. Neuronal degeneration, vacuolation of the neuropils, and pericellular and perivascular spaces were observed. In addition, the pyramidal and granular cell layers of the hippocampus and cerebellum, respectively, were found to have significantly reduced thickness. Furthermore, a significant decrease in the percentage area of the glial fibrillary acidic protein and a significant increase in the percentage area of caspase-3 were noted. On the other hand, co-treatment with SeNPs partially ameliorated these alterations. A significant reduction in malondialdehyde levels; a non- significant elevation in total antioxidant capacity; up-regulation, upregulation of Nrf2, GPx, and Bcl-2 and downregulation of Bax were recorded. Neuronal degeneration, vacuolation of neuropils, and pericellular spaces were reduced. The pyramidal and granular cell layers restored their normal thickness. The percentage area of the glial fibrillary acidic protein significantly increased, whereas that of caspase-3 significantly decreased. In conclusion, SeNPs have an ameliorative effect against melamine-induced neurotoxicity in albino rats.

Destructive effect of iron overload in brain tissue of albino rats: Ameliorative role of silver immobilized organo-modified casein nanocomposite as co-treating agent with Deferasirox

BackgroundIron (Fe) is one of the most essential trace elements in the body that play crucial role in organisms’ survival, however, excess deposition of it puts patients at higher risk of iron overload and tissue injury through production of reactive oxygen species (ROS), elevation of oxidative stress, development of endocrine disorders among which hypogonadism, and increased incidence of cells damage in vital organs. As deferasirox (DFX) is an approved Fe chelator drug, its inability to cross blood brain barrier (BBB) remains a definite obstacle against its use as Fe chelator in the brain. Lately, attention to nanoparticles usage in researches has been widely grown since their role in improving drug therapeutic effects and scavenging free radicals make them good candidates as chelating and antioxidant agents. AimsHerein, after induction of iron overload, organo-modified casein immobilized silver nanocomposite (Ag@Tr-CA) was designed and explored as combined therapy with DFX drug to develop its penetrating efficiency toward BBB and its Fe chelating affinity. Moreover, to distinguish the advanced antioxidant character as well as the beneficial impact of it on lowering brain’s oxidative stress. Meanwhile, its capability in regulating serum pituitary hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone (T), ameliorating DNA damage, and improving brain’s histopathological alterations was also assessed. MethodsThe physicochemical characteristics of Ag@Tr-CA was carried out using X-ray powder diffractometry (XRD), Fourier transform infrared (FTIR), dynamic light scattering (DLS), field emission scanning electron microscope (FE-SEM), and high-resolution transmission electron microscope (HR-TEM) analyses. Effect of iron overload and subsequent treatment with DFX + Ag@Tr-CA on brain of adult male albino rats were evaluated using colorimetric methods to determine brain Fe concentration and brain oxidative stress biomarkers. Assessment of serum Fe indices and serum pituitary hormones (FSH, LH, PRL) and T were estimated by ELISA technique. Determination of DNA damage in cerebral cortex cells was accomplished using the alkaline version of comet assay, while detection of brain’s histopathological alterations was performed by examination of H&E sections under light microscope. ResultsThe physicochemical characteristics of Ag@Tr-CA showing the proficiency of Ag nanoparticles (∼35 nm) in creating highly-ordered negatively charged micro-sized casein particles (∼450 μm). After induction of iron overload, DFX + Ag@Tr-CA combination efficiently down brain Fe concentration, brain oxidative stress markers, and DNA damage in cerebral cortex cells linked with improvements in brain histopathological alterations. Comparing DFX therapeutic action alone to its combination to whether Ag@Tr-CA or Tr-CA (organo-modified cross-linked casein nanoparticles) as co-treating agents revealed no significant effect on serum Fe indices, FSH, LH, PRL, and T against iron overload disease. ConclusionThe present results showed that combination of Ag@Tr-CA nanocomposite with DFX makes it a promising co-treating agent against iron overload through improving the physiological, molecular, and histological structure of the brain in iron overloaded rats.

Toxic Effects of Food azo dye Tartrazine on the Brain of Young Male Albino Rats: Role of Oxidative Stress

Background: Tartrazine is a synthetic colorant that is extensively used in food and pharmaceutical products all around the world. Children usually consume large amount of colored food products. The purpose of the current study was to evaluate the possible toxic effects of tartrazine on the brain of young albino rats. Material and methods: Eighteen young male albino rats were randomly divided into 3 equal groups; Group I (negative control group), Group II (positive control group): each rat received 1 ml distilled water once daily and Group III (tartrazine group): each rat received 320 mg/kg tartrazine dissolved in 1 ml distilled water once daily by oral gavage. After 4 weeks of daily administration, rats of all groups were sacrificed, and the brains were harvested and prepared for evaluation of oxidative stress markers; glutathione peroxidase (GPx) and malondialdehyde (MDA) as well as histopathological examination by light microscope. Results: The results of the study revealed significant decrease in GPx activity and significant increase in MDA level in tartrazine group as compared to control groups. This was associated with significant histopathological changes in the brain including neuronal apoptosis, cellular infiltration, vacuolations and congested vasculature. Conclusion: Tartrazine toxicity induced severe brain damage in young male albino rats in the form of affection of the general architecture of the brain associated with increased oxidative stress. Recommendations: It is recommended that consumption of foods containing food colorant tartrazine should be restricted especially for children.