Abdelghafar, N. S., R. I. Hamed, E. M. El-Saied, M. M. Rashad, N. A. E. Yasin, and P. A. Noshy, "Protective effects of zinc oxide nanoparticles against liver and kidney toxicity induced by oxymetholone, a steroid doping agent: Modulation of oxidative stress, inflammation, and gene expression in rats.", Toxicology and applied pharmacology, vol. 505, pp. 117574, 2025 Sep 19. Abstract

Oxymetholone, a synthetic anabolic steroid, is widely used for medical and performance-enhancing purposes but is associated with significant toxicity. Zinc oxide nanoparticles (ZnO-NPs) have attracted attention for their antioxidant and anti-inflammatory properties, which may counteract such toxic effects. This study investigates the protective role of ZnO-NPs against oxymetholone-induced liver and kidney damage in rats. Twenty-four rats were randomly assigned to four groups and treated orally as follows: control, oxymetholone (10 mg/kg), ZnO-NPs (5 mg/kg), and oxymetholone + ZnO-NPs. Oxymetholone administration significantly increased serum levels of urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Furthermore, oxidative stress markers, such as malondialdehyde (MDA), were significantly elevated, whereas reduced glutathione (GSH) levels were decreased in both hepatic and renal tissues. Oxymetholone exposure also upregulated the expression of pro-inflammatory and stress-related genes, including tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and nibrin (NBN). In contrast, it downregulated antioxidant genes such as nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), and superoxide dismutase (SOD). Histopathological examination revealed extensive liver and kidney damage, with immunohistochemistry demonstrating marked NF-κB expression. However, concurrent administration of ZnO-NPs mitigated these toxic effects by restoring antioxidant balance, modulating inflammatory pathways, and preserving tissue integrity. These findings suggest that ZnO-NPs have a protective role against oxymetholone-induced oxidative stress, inflammation, and tissue damage in hepatic and renal tissues.

Abdel-moneam, D. A., H. S. Khalefa, M. M. Rashad, G. E. Ali, D. W. Bashir, P. A. Noshy, and S. B. Mahmoud, "Dietary carvacrol essential oil alleviates thallium nitrate-induced toxicity in Oreochromis niloticus: Growth, hepatorenal, oxidative stress, gene expression, and histopathological study", Aquaculture, vol. 599, pp. 742175, 2025.
Khalaf, A. A. A., M. A. Elhady, Marwa A Ibrahim, E. I. Hassanen, R. E. Abdelrahman, and P. A. Noshy, "Quercetin protects the liver of broiler chicken against oxidative stress and apoptosis induced by ochratoxin A.", Toxicon : official journal of the International Society on Toxinology, vol. 251, pp. 108160, 2024. Abstract

Ochratoxin A (OTA) is a mycotoxin that causes major health concerns in human and animals. Quercetin (QUE) is a flavonoid that possesses antioxidant, anti-inflammatory and anti-apoptotic properties. This report aims to investigate the ameliorative effects of QUE against OTA-induced hepatotoxicity in broiler chicken. Forty broiler chicks were equally allocated into 4 groups: Group I (control), Group II (OTA), Group III (QUE) and Group IV (OTA + QUE). OTA (0.5 mg/kg) and QUE (0.5 g/kg) were incorporated into the chicken feed for 42 days. The results presented a significant decrease in body weight and elevation in feed conversion ratio, and a significant elevation of the activities of serum alanine aminotransferase and aspartate aminotransferase enzymes in the OTA birds. Additionally, there was a significant decrease in catalase activity and reduced glutathione content and a significant elevation in malondialdehyde level in the liver of OTA-exposed birds. Various hepatocellular lesions were also noticed in the OTA-exposed birds. OTA exposure up-regulated the phosphatase and tensin homologue (PTEN) and the pro-apoptotic genes and down-regulated the anti-apoptotic genes in the liver. The addition of QUE ameliorated most of the hepatotoxic effects of OTA.

Abdelrahman, R. E., A. A. A. Khalaf, M. A. Elhady, Marwa A Ibrahim, E. I. Hassanen, and P. A. Noshy, "Quercetin ameliorates ochratoxin A-Induced immunotoxicity in broiler chickens by modulation of PI3K/AKT pathway.", Chemico-biological interactions, vol. 351, pp. 109720, 2022. Abstract

Ochratoxin A (OTA) is a fungal secondary metabolite produced by certain species of Aspergillus and Penicillium, and exerts immunosuppressive effect on humans and animals. Quercetin (QUE) is one of the flavonoids produced as a plant-secondary metabolite. The present study was designed to evaluate the efficacy of QUE against the immunotoxic hazard of OTA in broiler chickens. Forty one-day-old broiler chicks were randomly and equally allocated into four groups; control, OTA (0.5 mg/kg feed), QUE (0.5 g/kg feed) and OTA + QUE (0.5 mg/kg OTA + 0.5 g/kg QUE). The results revealed that dietary OTA induced a significant decrease in the antibody response to Newcastle Disease (ND), Infectious Bronchitis (IB) and Avian Influenza (AI) vaccination and in the lymphoproliferative response to Phytohemagglutinin-P (PHA-P). Ochratoxin A also induced oxidative stress and lipid peroxidation in the bursa of Fabricius, spleen and thymus tissues of chickens as demonstrated by decreased CAT and GSH levels and increased TBARS content. In addition, administration of OTA resulted in apoptosis, which was evident by the increased expression level of PTEN, Bax and Caspase-3 genes and decreased expression level of PI3K, AKT and Bcl-2 genes. Furthermore, exposure to OTA resulted in various pathological lesions in the bursa of Fabricius, spleen and thymus of chickens. On the other hand, administration of QUE ameliorated most of the immunotoxic effects of OTAby its immunomodulatory, antioxidant and anti-apoptotic activities. Taken together, the results suggested that QUE potentially alleviated the OTA-induced immunotoxicity in broiler chickens, probably through amelioration of oxidative stress and activation of the PI3K/AKT signaling pathway.

Shehata, A. M., F. M. S. Salem, E. M. El-Saied, S. S. Abd El-Rahman, M. Y. Mahmoud, and P. A. Noshy, "Evaluation of the Ameliorative Effect of Zinc Nanoparticles against Silver Nanoparticle-Induced Toxicity in Liver and Kidney of Rats.", Biological trace element research, vol. 200, issue 3, pp. 1201-1211, 2022. Abstract

Silver nanoparticles (Ag-NPs) have various pharmaceutical and biomedical applications owing to their unique physicochemical properties. Zinc (Zn) is an essential trace element, a strong antioxidant, and has a primary role in gene expression, enzymatic reactions, and protein synthesis. The present study aims to explore the toxic effects of Ag-NPs (50 nm) on the liver and kidney of rats and also to evaluate the potential protective effect of Zn-NPs (100 nm) against these adverse effects. Forty adult Sprague-Dawley rats were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, and Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered daily by gavage for 90 days. The results showed that exposure to Ag-NPs increased serum ALT, AST, urea, and creatinine. Ag-NPs also induced oxidative stress and lipid peroxidation and increased inflammatory cytokines in hepatic and renal tissues. Moreover, histopathological and immunohistochemical examinations revealed various histological alterations and positive caspase-3 expressions in the liver and kidney following exposure to Ag-NPs. On the other hand, most of these toxic effects were ameliorated by co-administration of Zn-NPs. It was concluded that Ag-NPs have hepatotoxic and nephrotoxic effects in rats via different mechanisms including oxidative stress, inflammation, and apoptosis and that Zn-NPs can be used to alleviate these harmful effects by their antioxidative, anti-inflammatory, and antiapoptotic properties.

Noshy, P. A., N. A. E. Yasin, M. M. Rashad, A. M. Shehata, F. M. S. Salem, E. M. El-Saied, and M. Y. Mahmoud, "Zinc nanoparticles ameliorate oxidative stress and apoptosis induced by silver nanoparticles in the brain of male rats.", Neurotoxicology, vol. 95, pp. 193-204, 2023. Abstract

The current study was conducted to investigate the possible ameliorative role of zinc nanoparticles (Zn NPs) against silver nanoparticles (Ag NPs)-induced oxidative and apoptotic brain damage in adult male rats. Twenty-four mature Wistar rats were randomly and equally divided into four groups: control group, Ag NPs group, Zn NPs group, and Ag NPs + Zn NPs group. Rats were exposed to Ag NPs (50 mg/kg) and/or Zn NPs (30 mg/kg) daily by oral gavage for 12 weeks. The results revealed that exposure to Ag NPs significantly increased malondialdehyde (MDA) content, decreased catalase and reduced glutathione (GSH) activities, downregulated the relative mRNA expression of antioxidant-related genes (Nrf-2 and SOD), and upregulated the relative mRNA expression of apoptosis-related genes (Bax, caspase 3 and caspase 9) in the brain tissue. Furthermore, severe neuropathological lesions with a substantial increase in the caspase 3 and glial fibrillary acidic protein (GFAP) immunoreactivity were observed in the cerebrum and cerebellum of Ag NPs-exposed rats. Conversely, co-administration of Zn NPs with Ag NPs significantly ameliorated most of these neurotoxic effects. Collectively, Zn NPs can be used as a potent prophylactic agent against Ag NPs-induced oxidative and apoptotic neural damage.

Azouz, R. A., R. M. S. Korany, and P. A. Noshy, "Silica Nanoparticle-Induced Reproductive Toxicity in Male Albino Rats via Testicular Apoptosis and Oxidative Stress.", Biological trace element research, vol. 201, issue 4, pp. 1816-1824, 2023. Abstract

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.

Saleh, S. M., O. S. El-Tawil, M. B. Mahmoud, S. S. Abd El-Rahman, E. M. El-Saied, and P. A. Noshy, "Do Nanoparticles of Calcium Disodium EDTA Minimize the Toxic Effects of Cadmium in Female Rats?", Biological trace element research, vol. 202, issue 5, pp. 2228-2240, 2024. Abstract

The present study aims to investigate the ability of CaNa2EDTA (ethylenediaminetetraacetic acid) macroparticles and nanoparticles to treat cadmium-induced toxicity in female rats and to compare their efficacies. Forty rats were divided into 4 equal groups: control, cadmium, cadmium + CaNaEDTA macroparticles and Cd + CaNaEDTA nanoparticles. Cadmium was added to the drinking water in a concentration of 30 ppm for 10 weeks. CaNaEDTA macroparticles and nanoparticles (50 mg/kg) were intraperitoneally injected during the last 4 weeks of the exposure period. Every two weeks, blood and urine samples were collected for determination of urea, creatinine, metallothionein and cadmium concentrations. At the end of the experiment, the skeleton of rats was examined by X-ray and tissue samples from the kidney and femur bone were collected and subjected to histopathological examination. Exposure to cadmium increased the concentrations of urea and creatinine in the serum and the concentrations of metallothionein and cadmium in serum and urine of rats. A decrease in bone mineralization by X-ray examination in addition to various histopathological alterations in the kidney and femur bone of Cd-intoxicated rats were also observed. Treatment with both CaNaEDTA macroparticles and nanoparticles ameliorated the toxic effects induced by cadmium on the kidney and bone. However, CaNaEDTA nanoparticles showed a superior efficacy compared to the macroparticles and therefore can be used as an effective chelating antidote for treatment of cadmium toxicity.

Abdelrahman, R. E., A. A. A. Khalaf, M. A. Elhady, Marwa A Ibrahim, E. I. Hassanen, and P. A. Noshy, "Antioxidant and antiapoptotic effects of quercetin against ochratoxin A-induced nephrotoxicity in broiler chickens.", Environmental toxicology and pharmacology, vol. 96, pp. 103982, 2022. Abstract

The mycotoxin ochratoxin A (OTA) is produced by the fungi Aspergillus and Penicillium. The flavonoid quercetin (QUE) is distinguished by its antioxidant, anti-inflammatory, and antiapoptotic properties. This study was designed to determine whether QUE can protect broiler chickens against OTA-induced nephrotoxicity. Forty broiler chicks were randomly divided into four equal groups: control, OTA, QUE, and OTA + QUE. For 6 weeks, OTA (0.5 mg/kg) and/or QUE (0.5 g/kg) were added to the diet of chickens. The results demonstrated that OTA exposure increased serum levels of creatinine, uric acid, and blood urea nitrogen. OTA exposure also increased renal malondialdehyde content but decreased renal antioxidants. OTA-exposed chickens exhibited multiple pathological kidney lesions. Moreover, OTA exposure induced apoptosis in renal tissue, which was manifested by the up-regulation of proapoptotic genes and down-regulation of antiapoptotic genes via the suppression of the PI3K/AKT pathway. In addition, coadministration of QUE and OTA mitigated most of these nephrotoxic effects.

Noshy, P. A., A. A. A. Khalaf, Marwa A Ibrahim, A. M. Mekkawy, R. E. Abdelrahman, A. Farghali, A. A. - E. Tammam, and A. R. Zaki, "Alterations in reproductive parameters and steroid biosynthesis induced by nickel oxide nanoparticles in male rats: The ameliorative effect of hesperidin.", Toxicology, vol. 473, pp. 153208, 2022. Abstract

With recent progress in the manufacture and applications of nickel oxide nanoparticles (NiO NPs), concerns about their adverse effects are increasing. Hesperidin (HSP) is a citrus flavonoid that has a potent anti-inflammatory, antioxidant and free radical scavenging activities. This study aims to investigate the protective effect of HSP against testicular and spermatological damages induced by NiO NPs in male rats. Forty rats were randomly and equally divided into four groups: control, NiO NPs, HSP and NiO NPs + HSP. NiO NPs (100 mg/kg) and/or HSP (100 mg/kg) were given daily by gavage for 60 days. Exposure to NiO NPs induced marked reproductive toxicity in male rats that was manifested by increased sperm abnormalities and deterioration of sperm motility, count and viability. NiO NPs also increased lipid peroxidation and negatively affected the cellular antioxidant defense system in the testis of rats. The level of serum testosterone hormone was increased in NiO NPs-exposed rats. qPCR showed a marked downregulation in expression of steroidogenesis-related genes (CYP11A1, HSD3B and STAR) and a significant upregulation in expression of apoptosis-related gene (caspase-9) in testicular tissue of rats. Various pathological lesions and an increase in the number of PCNA-positive immune-reactive cells were also noticed in the testis of NiO NPs-exposed rats. Co-administration of HSP significantly ameliorated most of the NiO NPs-induced testicular damages and improved male fertility in rats.