Ameliorative effects of propolis and wheat germ oil on acute toxoplasmosis in experimentally infected mice are associated with reduction in parasite burden and restoration of histopathological changes in the brain, uterus, and kidney.

Toxoplasmosis continues to be a prevalent parasitic zoonosis with a global distribution. This disease is caused by an intracellular parasite known as Toxoplasma gondii, and the development of effective novel drug targets to combat it is imperative. There is limited information available on the potential advantages of wheat germ oil (WGO) and propolis, both individually and in combination, against the acute phase of toxoplasmosis. In this study, acute toxoplasmosis was induced in Swiss albino mice, followed by the treatment of infected animals with WGO and propolis, either separately or in combination. After 10 days of experimental infection and treatment, mice from all groups were sacrificed, and their brains, uteri, and kidneys were excised for histopathological assessment. Additionally, the average parasite load in the brain was determined through parasitological assessment, and quantification of the parasite was performed using Real-Time Polymerase Chain Reaction targeting gene amplification. Remarkably, the study found that treating infected animals with wheat germ oil and propolis significantly reduced the parasite load compared to the control group that was infected but not treated. Moreover, the group treated with a combination of wheat germ oil and propolis exhibited a markedly greater reduction in parasitic load compared to the other groups. Similarly, the combination treatment effectively restored the histopathological changes observed in the brain, uterus, and kidney, and the scoring of these reported lesions confirmed these findings. In summary, the present results reveal intriguing insights into the potential therapeutic benefits of wheat germ oil and propolis in the treatment of acute toxoplasmosis.

Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2).

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers' (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities.

Several negative outcomes are associated with current anti-epileptic medications. Epigallocatechin gallate (EGCG) is a plant-derived compound called catechin and has many medicinal activities, such as anti-inflammatory and antioxidant activities. Biosynthesized selenium nanoparticles are also showing their neuroprotective effect. The anti-epileptic effect of EGCG, alone or with SeNPs, is still debated. Here, we aimed to investigate the potential anti-seizure effect of biosynthesized SeNPs using EGCG (EGCG-SeNPs) against epileptic seizures and hippocampal damage, which is enhanced by pentylenetetrazole (PTZ) injection in mice. Mice were grouped as follows: control; PTZ-exposed group (epileptic model); EGCG + PTZ-treated group; sodium selenite (Na2SeO3) + PTZ-treated group; EGCG-SeNPs + PTZ-treated group; and valproic acid (VPA) + PTZ-treated group. EGCG-SeNPs administration showed anti-epileptic activity by increasing the latency time and reducing the seizure duration following the PTZ injection. Additionally, EGCG-SeNPs counteracted the PTZ-induced changes in oxidants and antioxidants. Moreover, EGCG-SeNPs inhibited the inflammatory response by suppressing the release of pro-inflammatory cytokines and decreasing the immunoreactivity of the glial fibrillary acidic protein and mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; Grin1), showing their inhibitory effect on epilepsy-associated inflammation. Moreover, EGCG-SeNPs reduced PTZ-induced neuronal apoptosis, as indicated by a reduction in the levels of pro-apoptotic proteins and an elevation of the anti-apoptotic protein. Moreover, EGCG-SeNPs administration significantly modulated the PTZ-induced changes in monoamine levels and acetylcholinesterase activity in the hippocampal tissue. The obtained findings suggest the anti-seizure activity of EGCG-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their neuromodulatory effect.

Biochemical and histopathological effects of copper oxide nanoparticles exposure on the bivalve Chambardia rubens (Lamarck, 1819).

Copper nanoparticles are widely incorporated into many applications, including air and liquid filters, wood preservatives, batteries, thermal and electrical conductivity, inks and skin products. Their potential toxicity and environmental fate, however, are poorly studied in the freshwater bivalves. The aim of the present study was to evaluate the different effects of copper oxide nanoparticles and ionic copper on the digestive glands and gills of the mussel Chambardia rubens. Mussels were treated with 100 and 1000 µg Cu L-1 of copper oxide nanoparticles (CuONPs) or ionic copper (Cu2+) for 3, 7, and 14 days. The Cu accumulation and markers of oxidative stress in the digestive glands and gills were evaluated. The results show that the digestive gland collected higher levels of the two forms of copper than the gills. Exposure to CuONPs or Cu2+ induced significant elevations in superoxide dismutase, glutathione peroxidase and lipid peroxidation. Notably, a significant decrease was observed in the glutathione levels after exposure to both copper forms. CuONPs only induced a significant increase in glutathione reductase and glutathione S-transferase. The ionic copper only induced a significant decrease in catalase activities in the gill tissues. Overall, CuONPs and Cu2+ provoked oxidative stress, and further research is needed to clarify their genotoxic and neurotoxic effects on freshwater mussels and other biota.

Comparative effects of finasteride and laser-irradiated silver nanoparticles on testicular function and histology in testosterone induced benign prostatic hyperplasia in rats.

AIMS: The objective of this study was to compare the effects of finasteride, a medication used to treat benign prostatic hyperplasia (BPH), and laser irradiated silver nanoparticles (AgNPs), a potential candidate for BPH therapy (Sanchez-Salas, 2017; Marghani et al., 2022) [1,2], on the sex hormone profiles, sperm quality, steroidogenesis, testicular oxidative stress, and histomorphology changes in BPH rats. MATERIALS AND METHODS: BPH was induced in male Sprague-Dawley (SD) rats via intramuscular (i.m.) injection of 5 mg/kg BW testosterone propionate (TP) for 14 days. Once the BPH model was induced, rats were divided into four groups (n = 6) as follows: the control group; the BPH group; the BPH/Fina group, which received 5 mg/kg BW finasteride by oral gavage daily for 14 days; and the BPH/AgNPs group, which received a daily intraperitoneal (i.p.) injection of 50 mg/kg BW AgNPs, followed by 5min of exposure to a 532 nm NIR laser in the prostatic area for the constitutive 14 days. KEY FINDINGS: On day 14, the BPH rats had a significant increase in prostate specific antigen (PSA), dihydrotestosterone, and prostate weights, while testicular weights and sperm quality were significantly lower than in the control rats. On day 28, laser irradiated AgNps treated BPH rats showed improved sex hormone balance, testicular weights, sperm quality, steroidogenesis, and an ameliorative effect on testicular histopathology compared to finasteride. SIGNIFICANCE: Surprisingly, these findings suggest that laser irradiated AgNPs can be used as an alternative therapy to finasteride for the treatment of BPH without causing negative effects on the testes.

Apigenin protects from hepatorenal damage caused by lead acetate in rats.

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects.

Photothermal therapeutic potency of plasmonic silver nanoparticles for apoptosis and anti-angiogenesis in testosterone induced benign prostate hyperplasia in rats.

AIMS: In this study, we used a near-infrared laser (NIR) to increase the potency of silver nanoparticles (AgNPs) to develop a novel, less invasive, and simple photothermal therapy technique for benign prostate hyperplasia (BPH). MATERIALS AND METHODS: The shape, particle size, and zeta-potential of polyvinylpyrrolidone coated-AgNPs (PVP-AgNPs) were determined using transmission electron microscopy (TEM), Zeta-potential, and Particle size analyzer (ELSZ). To induce BPH, thirty-six male Sprague-Dawley (SD) rats were given intramuscular (i.m) injections of testosterone propionate (TP) at 5 mg/kg body weight (b.w)/day suspended in 0.1 ml of olive oil for 14 days. Photothermal therapy with AgNPs-NIR for 14 days was carried out. Prostate size, prostate index (PI), dihydrotestosterone (DHT), prostate-specific antigen (PSA), gross, hepatic, and renal toxicity, as well as antioxidant activity, apoptosis, and angiogenesis markers in prostatic tissues were measured. Histological examinations of prostates and biocompatibility of NIR-AgNPs on vital organs were also performed. KEY FINDINGS: The aggregated spherical AgNPs with a mean size of 50-90 nm and a Zeta potential of -53.22 mV displayed high effectiveness in the NIR (532 nm-1 W) region by decreasing prostate size, PI, DHT, and PSA in BPH rats with no signs of gross, hepatic, or renal damage. As compared to alternative therapies, hyperthermia therapy increased antioxidant activities, induced apoptosis, inhibited angiogenesis, reduced histological alterations in the prostates of BPH rats, and improved biocompatibility of the vital organs. SIGNIFICANCE: The current study demonstrated the effectiveness of plasmonic AgNPs photothermal therapy in the treatment of BPH.

Potential Effects of Bisphenol A on the Heart and Coronary Artery of Adult Male Rats and the Possible Role of L-Carnitine.

Bisphenol A (BPA) is an environmental toxin utilized for the production of polycarbonate plastics and epoxy resins. Due to BPA's extensive production and environmental contamination, human exposure is unavoidable. The effects of low-dose of BPA on various body tissues and organs remain controversial. Our study investigated the potential of BPA to induce biochemical, histopathological, and immunohistochemical changes in the coronary artery and myocardium and the potential protective role of L-carnitine (LC). 24 adult Wistar albino male rats were divided equally into a control group, a BPA-treated group (40 mg/kg/d, by gavage for 4 weeks), and a BPA plus LC-treated group (received 40 mg/kg/d of BPA and 300 mg/kg/d of LC, by gavage for 4 weeks). BPA-exposed rats demonstrated structural anomalies in the coronary artery tissue including vacuolation of cells in the media and detachment of the endothelium of the intima. Congestion of blood vessels and infiltration by polynuclear cells were observed in the myocardium. There was an enhanced collagen deposition in both tissues indicating fibrosis. Immunohistochemical changes included enhanced eNOS and caspase-3 expression in the coronary artery and myocardium indicating vascular disease and apoptosis, respectively. Oxidative damage was evident in the coronary artery and the myocardium of BPA-treated rats, which was indicated by the reduced level of glutathione (GSH) and elevated malondydehyde (MDA) levels. The coadministration of LC significantly improved BPA-induced structural alterations and oxidative stress. In conclusion, BPA could potentially cause pathologic changes and oxidative damage in the coronary artery and myocardium, which could be improved by LC coadministration.

Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent.

OBJECTIVE: The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs). METHODS: SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na2SeO3 and characterized with Fourier transform infrared spectroscopy. Sixty male Swiss albino mice were then acclimatized for one week, injected with Ehrlich ascites tumor cells, and divided into four groups: EST, EST + cisplatin (5 mg/kg), EST + Ber (20 mg/kg), and EST + SeNPs-Ber (0.5 mg/kg). At the end of a 16-day observation period, 12 mice from each group were euthanized to analyze differences in the body weight, tumor size, gene expression, and oxidative stress markers in the four groups. Three mice from each group were kept alive to compare the survival rates. RESULTS: Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2 (Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group. CONCLUSION: Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.

S-Methylcysteine Ameliorates the Intestinal Damage Induced by Eimeria tenella Infection via Targeting Oxidative Stress and Inflammatory Modulators.

Avian coccidiosis is one of the major parasitic diseases in the poultry industry. The infection is caused by Eimeria species, and its treatment relies mainly on the administration of anticoccidial drugs, which can result in drug resistance and side effects. The recent trends in avian coccidiosis treatment is directed to the development of a new therapy using herbal compounds. S-Methylcysteine (SMC) is considered one of the organosulfur compounds in garlic that showed promising activity in the treatment of different pathological conditions via a wide range of anti-inflammatory and antioxidant mechanisms. In this study, the anticoccidial activity of SMC was investigated in Eimeria tenella-infected chickens compared to diclazuril as a widely used anticoccidial drug. In this regard, 14-day-old broilers were divided into six groups (n = 18). The first group (G1) was the healthy control group, while the second group (G2) was the non-infected SMC group treated at a dose of 50 mg/kg b.w. (high dose). Moreover, the third group (G3) was the positive control group (infected and non-treated). The fourth group (G4) was the infected group treated with SMC of 25 mg/kg b.w. (low dose), while the fifth group (G5) was the infected group treated with SMC of 50 mg/kg b.w. (high dose). Conversely, the sixth group (G6) was the diclazuril-treated group. The anticoccidial effects of SMC and diclazuril were evaluated by counting oocysts and recording the body weight gain, feed conversion ratio, clinical signs, lesions, and mortality rate. Interestingly, SMC showed potent anticoccidial activity, which was exemplified by reduction of oocyst count. Furthermore, the biochemical, antioxidant, and anti-inflammatory parameters in the cecal tissues were restored toward their control levels in G4, G5, and G6. Histopathological observation of cecal tissues was consistent with the aforementioned results revealing the ameliorative effect of SMC against E. tenella infection. This study concluded novel findings in relation to the anticoccidial role of SMC as a plant-based compound against the E. tenella-induced coccidiosis in broiler chickens combined with its antioxidative and anti-inflammatory properties. Further studies for exploring the mechanistic pathways involved in this activity and the potential benefits from its use in association with conventional anticoccidial drugs are warranted.

Size-Dependent Effect of Silver Nanoparticles on the Tumor Necrosis Factor α-Induced DNA Damage Response.

Silver nanoparticles (AgNPs) are widely used in many consumer products due to their anti-inflammatory properties. Therefore, the effect of exposure to AgNPs should be investigated in diseased states in addition to healthy ones. Tumor necrosis factor-α (TNFα) is a major cytokine that is highly expressed in many diseased conditions, such as inflammatory diseases, sepsis, and cancer. We investigated the effects of two different sizes of AgNPs on the TNFα-induced DNA damage response. Cells were exposed to 10 and 200 nm AgNPs separately and the results showed that the 200 nm AgNPs had a lower cytotoxic effect with a higher percent of cellular uptake compared to the 10 nm AgNPs. Moreover, analysis of reactive oxygen species (ROS) generation and DNA damage indicated that TNFα-induced ROS-mediated DNA damage was reduced by 200 nm AgNPs, but not by 10 nm AgNPs. Tumor necrosis factor receptor 1 (TNFR1) was localized on the cell surface after TNFα exposure with or without 10 nm AgNPs. In contrast, the expression of TNFR1 on the cell surface was reduced by the 200 nm AgNPs. These results suggested that exposure of cells to 200 nm AgNPs reduces the TNFα-induced DNA damage response via reducing the surface expression of TNFR1, thus reducing the signal transduction of TNFα.

Silver nanoparticles reduce the apoptosis induced by tumor necrosis factor-α.

Silver nanoparticles (AgNPs) are widely known to have anti-inflammatory properties, but the exact mechanism underlying this anti-inflammatory effect is not clearly understood. Tumor necrosis factor-α (TNFα) is a major pro-inflammatory cytokine that is expressed in the early stage of cell inflammation and induces apoptosis by several known pathways. Our study aimed to investigate the effect of AgNPs on the response of lung epithelial cells to TNFα and the molecular mechanism of this response. Lung epithelial cell line NCI-H292 cells were exposed to AgNPs (5 µg/mL) and/or TNFα (20 ng/mL) for 24 h, then cellular uptake was analyzed using flow cytometry. Our results showed that AgNPs were taken up by cells in a dose-dependent manner and that the cellular uptake ratio of AgNPs was significantly increased in the presence of TNFα. Apoptosis assays indicated that exposure to AgNPs significantly decreased the apoptotic effect of TNFα. Confocal microscopy was used to localize the tumor necrosis factor receptor 1 (TNFR1) and revealed that TNFR1 localized on the surface of cells exposed to TNFα. In contrast, TNFR1 localized inside cells exposed to both AgNPs and TNFα, with very few receptors scattered on the cell membrane. The results indicated that AgNPs reduced the cell surface TNFR1 expression level. The results suggested that the reduction of surface TNFR1 reduced cellular response to TNFα, resulting in an anti-apoptotic effect.