Novel insights on the probable mechanism associated with histamine oral model-inducing neuropathological and behavioral toxicity in rats.

Histamine (HIS) is an important chemical mediator that causes vasodilation and contributes to anaphylactic reactions. Recently, HIS is an understudied neurotransmitter in the central nervous system, and its potential role in neuroinflammation and neurodegeneration is a critical area of research. So, the study's goal is to investigate the consequences of repeated oral intake of HIS on the rat's brain and explore the mechanistic way of its neurotoxicity. Thirty male rats were divided into three groups (n = 10). The following treatments were administered orally to all rats every day for 14 days. Group (1) was given distilled water, whereas groups (2 & 3) were given HIS at dosage levels 250 and 500 mg/kg body weight (BWT), respectively. Brain tissue samples were collected at 7- and 14-days from the beginning of the experiment. Our results revealed that continuous oral administration of HIS at both doses for 14 days significantly reduced the BWT and induced severe neurobehavioral changes, including depression, dullness, lethargy, tremors, abnormal walking, and loss of spatial learning and memory in rats. In all HIS receiving groups, HPLC data showed a considerable raise in the HIS contents of the brain. Additionally, the daily consumption of HIS causes oxidative stress that is dose- and time-dependent which is characterized by elevation of malondialdehyde levels along with reduction of catalase activity and reduced glutathione levels. The neuropathological lesions were commonly observed in the cerebrum, striatum, and cerebellum and confirmed by the immunohistochemistry staining that demonstrating moderate to strong caspase-3 and inducible nitric oxide synthase expressions in all HIS receiving groups, mainly those receiving 500 mg/kg HIS. NF-κB, TNF-α, and IL-1ß gene levels were also upregulated at 7- and 14-days in all HIS groups, particularly in those getting 500 mg/kg. We concluded that ROS-induced apoptosis and inflammation was the essential mechanism involved in HIS-mediated neurobehavioral toxicity and histopathology.

Macro, Micro, and Nano-Inspired Bioactive Polymeric Biomaterials in Therapeutic, and Regenerative Orofacial Applications.

Introducing dental polymers has accelerated biotechnological research, advancing tissue engineering, biomaterials development, and drug delivery. Polymers have been utilized effectively in dentistry to build dentures and orthodontic equipment and are key components in the composition of numerous restorative materials. Furthermore, dental polymers have the potential to be employed for medication administration and tissue regeneration. To analyze the influence of polymer-based investigations on practical medical trials, it is required to evaluate the research undertaken in this sector. The present review aims to gather evidence on polymer applications in dental, oral, and maxillofacial reconstruction.

Silica Nanoparticle-Induced Reproductive Toxicity in Male Albino Rats via Testicular Apoptosis and Oxidative Stress.

Amorphous silica nanoparticles (SiNPs) are being utilized in different fields such as medicine, cosmetics, and foods. However, the causes and mechanisms underlying SiNP testicular damage remain largely unclear. In the present study, we aimed to investigate this issue. Thirty male rats were randomly divided into three groups: control group (n = 10), 500 ppm SiNP-treated group (n = 10), and 1000 ppm SiNP-treated group (n = 10). SiNPs were given orally in drinking water for 30 days. Micronucleus assay was performed on blood RBCs. The concentrations of testicular malondialdehyde (MDA) and glutathione (GSH) and catalase (CAT) activity were measured. Moreover, the histopathological alterations and the expression of apoptotic (caspase-3) and pro-inflammatory and oxidative stress markers (iNOS) in testes and epididymis were analyzed and compared between the three groups. The results showed an increased level of micronucleus frequencies in the 1000 ppm-treated group, as well as increased levels of MDA and decreased activity of CAT and GSH content in testicular tissues in the 1000 ppm-treated group, suggesting DNA damage and oxidative stress mechanisms. Also, there were significant testicular histopathological alterations in this group. Furthermore, 1000-ppm SiNPs could enhance testicular apoptosis, inflammation, and oxidative stress by increasing the expression of apoptotic, pro-inflammatory, and oxidative stress genes including caspase 3 and iNOS in the examined tissue. The lower concentration of SiNPs did not produce any significant biochemical, histopathological, or immunohistochemical alterations whereas 1000-ppm SiNPs resulted in significant testicular changes by exacerbating apoptotic, inflammatory, and oxidative stress-mediated testicular damage.

Selenium nanoparticles impart robust neuroprotection against deltamethrin-induced neurotoxicity in male rats by reversing behavioral alterations, oxidative damage, apoptosis, and neuronal loss.

This study investigated the neuroprotective role of selenium nanoparticles (SeNPs) on deltamethrin-induced neurotoxicity in rats. A total of 32 adult male Wister rats were allocated into the following four groups: 1) control, 2) deltamethrin (0.6 mg/kg), 3) SeNPs (0.5 mg/kg), and 4) deltamethrin + SeNPs. All agents were administered orally three times per week for 2 months. Locomotor behavior, anxiety-like behavior, biochemical parameters, including brain oxidative damage biomarkers (Malondialdehyde (MDA) and reduced glutathione (GSH)), brain acetylcholinesterase (AChE), and brain genotoxicity were evaluated. The gene expression levels of IGF-1 and Bcl2 were also determined. Moreover, a brain histopathological examination associated with the immunohistochemical determination of Bax in brain tissue was performed. Deltamethrin-intoxicated rats showed a reduction in the locomotor activity associated with a highly anxious state. They also displayed a disturbance in the brain redox state with a decrease in the brain AChE levels and a high DNA fragmentation percentage. Furthermore, they showed a decrement in the immunohistochemical GFAP levels as well as IGF-1 and Bcl2 gene expression levels with an increase in the immunohistochemical Bax levels. All these changes were confirmed by brain histopathology. Interestingly, SeNPs ameliorated all these changes and restored the normal brain architecture. In conclusion. SeNPs possess a potent medicinal activity due to their antioxidant and anti-inflammatory activity. Therefore, SeNPs can be a potential agent in ameliorating deltamethrin-induced neurotoxicity.

Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats.

Emamectin Benzoate (EMB) is an avermectin insecticide widely used in agriculture and veterinary medicine. Hesperidin (HSP) is a flavanone glycoside predominantly found in citrus fruits and has various beneficial health effects. The current research was conducted to study the neurobehavioral toxic effects of EMB in rats and also to evaluate the protective effect of HSP against these toxic effects. Sixty Sprague-Dawley rats were randomly divided into 4 equal groups: control group, EMB group, HSP group, and EMB + HSP group. EMB (8.8. mg/kg) and/or HSP (100 mg/kg) were administered daily by gavage for 8 weeks. The behavioral assessment demonstrated the adverse effects of EMB on the behavioral, motor, and cognitive brain functions. Exposure to EMB also decreased the activity of antioxidants (catalase and reduced glutathione) and increased the malondialdehyde level in nervous tissue. Moreover, EMB increased the level of inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) and decreased brain-derived neurotrophic factor (BDNF) levels in rats' brains. On the other hand, concurrent administration of HSP ameliorated the toxic effects of EMB as indicated by improvements in neural functions and reduction of oxidative stress and inflammation. The study concluded that exposure to EMB induces toxic effects in the brain of rats and that HSP has a protective effect against these toxic effects.

Ameliorative effect of ZnO-NPs against bioaggregation and systemic toxicity of lead oxide in some organs of albino rats.

Lead is one of the major environmental pollutions worldwide, particularly in developing countries. Though, various occupational and public health measures have been undertaken to control lead exposure. The present study is designed to investigate the role of zinc oxide nanoparticles (ZnO-NPs) to reduce the bioaggregation of lead in the brain, liver, and kidneys and prevent these organ oxidative damage and apoptosis. Twenty male Wistar rats were grouped into 4 gatherings and exposed to the following materials daily on the skin for 2 weeks: 1-normal saline, 2-ZnO-NPs, 3-PbO, and 4-ZnO-NPs+ PbO. Topical application of PbO to rats increased lead contents in blood and different organs causing remarkable oxidative stress damage, apoptosis, and histopathological alterations in these organs. Moreover, PbO-receiving group showed strong positive caspase-3 protein expression with up-regulation of mRNA levels of BAX and COX-2. Co-treatment of ZnO-NPs with PbO could diminish the toxicologic parameters and the above-mentioned immune marker and gene expression levels. Our data suggest the role of ZnO-NPs cream to reduce the risk of lead dermal exposure via preventing absorption and accumulation of it in the internal organs so that it protects these organs from further damage.

Toxic Impacts of Amorphous Silica Nanoparticles on Liver and Kidney of Male Adult Rats: an In Vivo Study.

The toxic effects of the amorphous silica nanoparticles have not been thoroughly studied. Moreover, the majority of the in vivo investigations were performed using an inhalation exposure method. The current study aimed to explore the potential toxic effects of silica nanoparticles (SiNPs) after the treatment of adult male rats with two different concentrations (500 and 1000 ppm) via drinking water for 28 days. The genotoxicity, antioxidant status, and liver and kidney functions were assessed. Besides, histopathological and immunohistochemical evaluations were performed. The results showed a significant elevation in the malondialdehyde (MDA) level concurrent with a reduction in total reduced glutathione (GSH) concentration and catalase activity in the 1000-ppm SiNP-exposed rats as well as increase in ALT and AST activity confirmed by various histopathological alterations detected in liver. Also, in the 1000-ppm SiNP-exposed animals, there was an elevation in urea and creatinine levels confirmed by histopathological alterations detected in kidneys. Immunohistochemical findings in both liver and kidneys indicated strong expression of caspase-3 in the 1000-ppm SiNP-treated rats compared with the control and 500-ppm SiNP-treated groups. Such findings indicated that the 1000-ppm SiNPs exerted severe hepato-renal toxic impacts when compared with the control and 500-ppm SiNP-exposed rats.

Nano selenium protects against deltamethrin-induced reproductive toxicity in male rats.

Greater understanding of the efficiency of nanoparticles will assist future research related to male reproductive performance. The current study was performed to assess the potency of selenium nanoparticles (SeNPs) in alleviating deltamethrin (DLM)-induced detrimental effects on sperm characteristics, oxidative status, sexual behavior, and the histological structure of the testes and epididymis in male rats. Thirty-two male Wister rats were divided into four groups according to treatment received orally by gavage 3 times/week for 60 days; control, DLM (0.6 mg/kg bwt), SeNPs (0.5 mg/kg bwt), and DLM-SeNPs groups. DLM caused a significant reduction in sperm count, motility, and viability percent, as well as in body weight and serum testosterone level, blood total antioxidant capacity (TAC), and glutathione peroxidase (GPx) activity. The DLM-treated group showed a significant increase in blood malondialdehyde (MDA) concentration and sperm abnormalities (%), as well as a significant reduction in sexual activity, manifested as an increase in mount, intromission, or ejaculation latency and a reduction in mount or intromission frequency. These toxic effects were confirmed by histological alterations, represented by a significant reduction in the diameter of the seminiferous tubules and spermatogenesis. Conversely, treatment with SeNPs improved DLM-induced negative effects on sperm characteristics, testosterone, and antioxidant biomarkers, as well as behavioral and histopathological alterations. The SeNPs treated group showed improved semen parameters, antioxidant status, and sexual performance. In conclusion, SeNPs may represent an effective treatment for reducing the detrimental effects of DLM on male fertility, and lead to enhanced male reproductive performance.

Ameliorative Effect Of Zinc Oxide Nanoparticles Against Dermal Toxicity Induced By Lead Oxide In Rats.

BACKGROUND: Recently, several studies demonstrate the possible role of zinc oxide (ZnO) in the protection of several skin diseases, but less is known about the role of ZnO nanoparticles in the inflammatory skin disease. So, this study was designed to confirm the pivotal role of the nano zinc oxide cream in the alleviation of lead oxide (PbO) induced-allergic dermatitis in rats. MATERIALS AND METHODS: Two concentrations (1% and 6%) of ZnONPs creams were prepared and characterized prior to being used in the study. A total number of 30 male Wistar rats were randomly divided into six groups. Group 1 (negative control), groups 2&3 (either 1% or 6% ZnONPs control groups), group 4 (PbO), groups 5&6 (co-treatment of each ZnONPs concentration+PbO). All rats in different groups were observed daily to determine the severity of dermal gross lesions. Histopathological studies, mRNA analysis, and oxidative stress evaluations were performed on the affected skin tissue. Immunohistochemical studies were performed to evaluate the expression of cluster of differentiation CD4, CD8 and intercellular adhesion molecules ICAM-1 in different groups. RESULTS: PbO caused extensive skin oxidative damage manifested by a significant increase in MDA level with a decrease in GSH content and CAT activity. The results of histopathological and immunohistochemical examinations revealed that topical application of PbO for 14 days led to severe allergic dermatitis with remarkable elevations in the number of CD4+ T-helper, CD8+ T-cytotoxic lymphocytes, and ICAM-1 expression. On the other hand, noticeable improvements were recorded in all the previous toxicopathological parameters among the groups treated by either 1% or 6% ZnO-NPs cream. However, the best results were observed in the group treated with 1% ZnO-NPs cream. CONCLUSION: Our findings suggest that 1% of ZnO-NPs cream is safe when applied topically on the inflamed skin. Moreover, it had anti-inflammatory and antioxidant effects so that, it is recommended to use the 1% ZnO-NPs cream to avert the dermal toxicity-induced by PbO.

Histopathological, biochemical and molecular studies on the toxic effect of used engine oil on the health status of Oreochromis niloticus.

The accidental spilling of petroleum oils into natural water resources expose fishes in the effluent area to serious problems.. Oreochromis niloticus were used in the current study as a model to investigate the toxicity of used engine oil and to evaluate the protective role of vitamin C against this toxicity. The oil concentration used in this study was previously determined to be 0.25 ml/l by 96 h-LC50. After 21 days of engine oil exposure, haematological and biochemical analyses revealed significant reduction in RBCs counts, haemoglobin concentrations and total proteins. However, ALT, AST and glucose levels were significantly increased by the end of the experiment indicating the damaging effects of the oil on fish tissues. Oxidative stress biomarkers were also measured; liver CAT activity was significantly decreased in the oil exposed group compared to control group, while MDA levels were significantly elevated. Histopathological examination showed the presence of several alterations in hepatic and branchial tissues in exposed group compared to the control group. Significant elevations in CYP1 A1 mRNA expression levels in hepatic tissue were also detected in the group exposed to used engine oil compared to the control group. However, supplementation of fishexposed to used engine oil with vitamin Csignificantly enhance the biochemical, oxidative and histological parameters.