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2022
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.

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.

2021
Khalaf, A. A. A., M. A. Elhady, E. I. Hassanen, A. A. Azouz, M. A. Ibrahim, M. K. Galal, P. A. Noshy, and R. A. Azouz, "Antioxidant Role of Carvacrol Against Hepatotoxicity and Nephrotoxicity Induced by Propiconazole in Rats.", Revista Brasileira de Farmacognosia, vol. 31, pp. 67–74, 2021.
Zaki, A. R., A. A. A. Khalaf, M. A. Ibrahim, A. M. Mekkawy, and P. A. Noshy, "Histopathological, immunohistochemical and molecular changes in the lung, heart and skin of drowned rats at different postmortem intervals.", International Journal of Medical Toxicology & Legal Medicine, vol. 24, pp. 34-48, 2021.
Noshy, P. A., and R. A. Azouz, "Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats.", Neurotoxicology and teratology, vol. 86, pp. 106981, 2021. Abstract

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-1β) 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.

Noshy, P. A., "Postmortem expression of apoptosis-related genes in the liver of mice and their use for estimation of the time of death.", International journal of legal medicine, vol. 135, issue 2, pp. 539-545, 2021. Abstract

PURPOSE: A major challenge in forensic medicine is to estimate the postmortem interval (PMI). Several approaches had been tried to determine the time of death, including physical and chemical changes. This study aims to explore the postmortem changes in the expression of apoptosis-related genes in the liver of mice and to use these changes for estimation of the PMI.

METHODS: Hepatic tissue was collected from sacrificed mice immediately after death (the control group) and at 3, 6, 9, 12, 18, and 24 hours after death. Four apoptosisrelated genes were selected as target genes, which are Caspase 3 (Casp3), B cell leukemia/ lymphoma 2 (Bcl2), BCL2-associated X protein (Bax), and Transformation related protein 53 (Trp53), and their relative expression was measured using quantitative PCR. miR-122 was used as a reference gene for normalization of the Ct (threshold cycle) values of the target genes.

RESULTS: The results revealed that the postmortem expression of Casp3 increased in a time-dependent manner; the expression of Bax increased from 3 to 18 hours followed by a decrease at 24 hours after death; the expression of Bcl2 decreased in a time-dependent manner after death; the expression of Trp53 increased from 3 to 6 hours and then started to decrease from 9 to 24 hours after death.

CONCLUSION: Based on the observed changes in the expression level of these genes, mathematical models were established to estimate the PMI. Further research is needed to investigate these markers and mathematical models in human tissues.

Shehata, A. M., F. M. S. Salem, E. M. El-Saied, S. S. Abd El-Rahman, M. Y. Mahmoud, and P. A. Noshy, "Zinc Nanoparticles Ameliorate the Reproductive Toxicity Induced by Silver Nanoparticles in Male Rats.", International journal of nanomedicine, vol. 16, pp. 2555-2568, 2021. Abstract

INTRODUCTION: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects.

METHODS: Forty adult male rats were used in this study; they were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered orally for 90 days.

RESULTS: The results revealed that exposure to Ag-NPs adversely affected sperm motility, morphology, viability, and concentration. Ag-NPs also induced oxidative stress and lipid peroxidation in testicular tissue. The exposure to Ag-NPs decreased serum FSH, LH, and testosterone hormones. Additionally, comet assay revealed DNA degeneration in the testicular tissue of rats exposed to Ag-NPs. Histopathological examination showed various histological alterations in the testes of rats intoxicated with Ag-NPs. Furthermore, co-administration of Zn-NPs ameliorated most of the toxic effects of Ag-NPs via their antioxidative capacity.

2019
Elhady, M. A., A. A. A. Khalaf, M. M. Kamel, and P. A. Noshy, "Carvacrol ameliorates behavioral disturbances and DNA damage in the brain of rats exposed to propiconazole.", Neurotoxicology, vol. 70, pp. 19-25, 2019 01. Abstract

Propiconazole (PCZ) is an ergosterol biosynthesis inhibiting fungicide. Carvacrol (CAR) is a monoterpenoid phenol that has various beneficial health effects. The current research was designed to study the impact of PCZ on the behavior of rats and its ability to induce DNA damage in neurons as well as to clarify the ameliorative effect of CAR against these toxic impacts. Sixty Sprague-Dawley rats were randomly and equally divided into 4 experimental groups and treated daily by oral gavage for 2 months as follows: Group 1 (control); group 2 treated with PCZ (75 mg/kg); group 3 treated with CAR (50 mg/kg) and group 4 treated with both PCZ and CAR. Behavioral tests demonstrated that exposure to PCZ had a deleterious effect on psychological, motor and cognitive neural functions. Additionally, antioxidant enzyme activities, SOD and GSH-Px, were declined in brain tissue following exposure to PCZ. Moreover, comet assay revealed a high percent of DNA damage in the brain of rats exposed to PCZ. On the other hand, CAR administration ameliorated the harmful effects induced by PCZ through a protective mechanism that involved the improvement of neural functions and attenuation of oxidative stress and DNA damage.

2018
Noshy, P. A., M. A. Elhady, A. A. A. Khalaf, M. M. Kamel, and E. I. Hassanen, "Ameliorative effect of carvacrol against propiconazole-induced neurobehavioral toxicity in rats.", Neurotoxicology, vol. 67, pp. 141-149, 2018 07. Abstract

Propiconazole (PCZ) is a triazole fungicide extensively used in agriculture. Carvacrol (CAR) is a naturally occurring phenolic monoterpene which has various biological and pharmacological effects. The present study was designed to investigate the neurobehavioral toxic effects of PCZ in albino rats and to evaluate the ameliorative role of CAR against such toxic effects. Sixty adult male rats were used in this investigation; they were randomly and equally divided into 4 groups: control group, PCZ group, CAR group and PCZ + CAR group. PCZ (75 mg/kg) and/or CAR (50 mg/kg) were administered daily by oral gavage for 8 weeks. Behavioral investigation clearly demonstrated the negative impact of PCZ on psychological, motor and cognitive brain functions. Exposure to PCZ also adversely affected the measured oxidative stress and lipid peroxidation parameters in brain tissue. A significant decrease in activity of acetylcholinesterase enzyme in neural tissue was also observed in PCZ-exposed rats. Histopathological examination of the cerebrum, cerebellum, and hippocampus showed various histopathological lesions after exposure to PCZ which were confirmed by immunohistochemical examination. On the other hand, co-administration of CAR ameliorated most of the undesirable effects of PCZ.

2017
Morgan, A., Mona K Galal, H. A. Ogaly, Marwa A Ibrahim, R. M. Abd-Elsalam, and P. Noshy, "Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.", Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 93, pp. 779-787, 2017 Sep. Abstract

Although the widespread use of titanium dioxide nanoparticles (TiO NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\Kg BW), group III received TiO2 NPs plus tiron (470mg\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-β1 (TGFβ1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFβ1 and MMP9. Oral administration of tiron to TiO NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO NPs through its radical scavenging and metal chelating potency.

Morgan, A. M., Marwa A Ibrahim, and P. A. Noshy, "Reproductive toxicity provoked by titanium dioxide nanoparticles and the ameliorative role of Tiron in adult male rats.", Biochemical and biophysical research communications, vol. 486, issue 2, pp. 595-600, 2017 04 29. Abstract

Titanium dioxide nanoparticles (TDN) are widely used in paints, plastics, ceramics, cosmetics, printing ink, rubber and paper. Tiron is a water soluble metal chelator and antioxidant. This study was designed to investigate the reproductive toxicity of TDN in male albino rats and the ameliorative role of Tiron to minimize such toxic effects. Eighty adult male albino rats were assigned into 4 equal groups, group 1: control; group 2: received TDN at 100 mg/kg/day orally for 8 weeks; group 3: received Tiron at 470 mg/kg/day intraperitoneally for 2 weeks (the last 2 weeks of the experimental period); group 4: received both TDN and Tiron by the same previously mentioned dose, route and duration. The results revealed that TDN provoked reproductive toxicity which was proved by the deteriorated spermogram picture, high incidence of micronucleated RBCs, elevated oxidative stress parameters and up regulation of Testin gene. Whereas, Tiron co-treatment ameliorated most of these toxic alterations. Our findings highlighted the protective role of tiron against TDN intoxication.