Publications by authors named "Mona K Galal"

21 Publications

  • Page 1 of 1

The ameliorative effect of N-acetylcysteine against penconazole induced neurodegenerative and neuroinflammatory disorders in rats.

J Biochem Mol Toxicol 2021 Aug 15:e22884. Epub 2021 Aug 15.

Toxicology and Forensic Medicine Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Penconazole (PEN) is a widely used systemic fungicide to treat various fungal diseases in plants but it leaves residues in crops and food products causing serious environmental and health problems. N-acetylcysteine (NAC) is a precursor of the antioxidant glutathione in the body and exerts prominent antioxidant and anti-inflammatory effects. The present study aimed to explore the mechanistic way of NAC to ameliorate the PEN neurotoxicity in male rats. Twenty-eight male rats were randomly divided into four groups (n = 7) and given the treated material via oral gavage for 10 days as the following: Group I (distilled water), Group II (50 mg/kg body weight [bwt] PEN), Group III (200 mg/kg bwt NAC), and Group IV (NAC + PEN). After 10 days all rats were subjected to behavioral assessment and then euthanized to collect brain tissues to perform oxidative stress, molecular studies, and pathological examination. Our results revealed that PEN exhibits neurobehavioral toxicity manifested by alteration in the forced swim test, elevated plus maze test, and Y-maze test. There were marked elevations in malondialdehyde levels with reduction in total antioxidant capacity levels, upregulation of messenger RNA levels of bax, caspase 3, and caspase 9 genes with downregulation of bcl2 genes. In addition, brain sections showed marked histopathological alteration in the cerebrum and cerebellum with strong bax and inducible nitric oxide synthetase protein expression. On the contrary, cotreatment of rats with NAC had the ability to improve all the abovementioned neurotoxic parameters. The present study can conclude that NAC has a neuroprotective effect against PEN-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic effect. We recommend using NAC as a preventive and therapeutic agent for a wide variety of neurodegenerative and neuroinflammatory disorders.
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http://dx.doi.org/10.1002/jbt.22884DOI Listing
August 2021

Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model.

J Ethnopharmacol 2021 Oct 7;278:114318. Epub 2021 Jun 7.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt. Electronic address:

Ethnopharmacological Relevance: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS).

Aim Of The Study: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model.

Materials And Methods: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured.

Results: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS.

Conclusions: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.
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http://dx.doi.org/10.1016/j.jep.2021.114318DOI Listing
October 2021

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect.

Chin Med 2021 Apr 29;16(1):36. Epub 2021 Apr 29.

Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.

Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS).

Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.

Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.
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http://dx.doi.org/10.1186/s13020-021-00444-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086310PMC
April 2021

Ameliorative effect of N-acetylcysteine against glyphosate-induced hepatotoxicity in adult male albino rats: histopathological, biochemical, and molecular studies.

Environ Sci Pollut Res Int 2021 Aug 2;28(31):42275-42289. Epub 2021 Apr 2.

Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Glyphosate (GLP) is the most commonly used herbicide that presents many hazards to the environment and living organisms. The present study aimed to explore hepatotoxic properties of GLP on adult albino rats, and the ability of N-acetylcysteine (NAC) to ameliorate these toxic effects. Thirty mature male albino rats were distributed into 3 groups (10 rats/group): Group I (C) a negative control, Group II (GLP) orally administered Roundup 0.8503 ml/kg/day which contain GLP (375 mg/kg) (1/10 of LD) by gavage needle, and Group III (NAC+ GLP) received NAC (160 mg/kg, 1h before Roundup) by gavage needle and Roundup (0.8503 ml/kg) orally for 6 weeks. Blood and liver samples were collected and processed for biochemical, histopathological, ultrastructural, and immunohistochemical investigations. Group II displayed a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels, as well as overexpression of apoptotic markers. The total antioxidant capacity "TAC" and mRNA expression of NRF2 were significantly decreased. Concerning the histopathological findings, there were various degenerative changes as the hepatocytes showed hydropic swelling with nuclear pyknosis. These alterations were confirmed ultrastructurally as most of the cytoplasmic organelles were lost and the mitochondria appeared to deteriorate. Immunohistochemical results showed intense immunoreactivity against proliferating cell nuclear antigen (PCNA) and caspase-3. NAC administration before GLP partially ameliorates these alterations. ALT, AST, and MDA levels as well as expression of apoptotic markers were significantly reduced. TAC and mRNA expression of NRF2 were significantly increased. Histopathological alterations were partially improved as the hepatocytes returned normal and ultrastructurally they showed nearly normal cytoplasmic organelles. Additionally, the intense expression of PCNA and caspase-3 was significantly reduced. We concluded that NAC can ameliorate most of the adverse effects of GLP exposure through its antioxidant property and free radicals scavenging capacity.
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http://dx.doi.org/10.1007/s11356-021-13659-2DOI Listing
August 2021

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

Environ Sci Pollut Res Int 2021 Jul 15;28(28):37940-37952. Epub 2021 Mar 15.

Department of Toxicology& Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

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.
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http://dx.doi.org/10.1007/s11356-021-13399-3DOI Listing
July 2021

Atrazine-induced cell-mediated immunotoxicity in rabbits and the ameliorating role of glycyrrhizic acid.

Environ Sci Pollut Res Int 2021 Jun 23;28(24):32027-32034. Epub 2021 Feb 23.

Toxicology and Forensic Medicine Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

The present study aimed to explain the mechanisms involved in cell-mediated immunotoxicity of atrazine (ATR) in rabbits and to evaluate the ameliorative role of glycyrrhizic acid (GA) against such toxic effects. Forty rabbits were assigned into 4 equal groups: control, ATR, GA, and ATR + GA groups. ATR (2475 ppm) and GA (60 μg of GA/ml of water) were administrated via food and drinking water, respectively, for 60 consecutive days. The cell-mediated immunotoxicity of ATR was clarified by the induced thymus immunotoxicity through downregulation of interleukin (IL)-9 gene and interferon-γ (IFN-γ) gene expression, upregulation in caspase-3, and significant decrease in the total leukocytic and lymphocyte counts. Histopathological investigations demonstrated severe depletion of lymphoid follicles in the medulla of the thymus gland. On the other hand, co-administration of GA for group 4 improved most of the undesirable impacts of ATR. In conclusion, the alteration in IL-9/IFN-γ expression may involve ATR-induced thymocyte apoptosis which may explain the mechanisms of ATR-induced cell-mediated immunotoxicity with a possible amelioration influence of GA administration.
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http://dx.doi.org/10.1007/s11356-021-12999-3DOI Listing
June 2021

The protective effects of Terminalia laxiflora extract on hepato-nephrotoxicity induced by fipronil in male rats.

Environ Sci Pollut Res Int 2020 Nov 10;27(31):39507-39515. Epub 2020 Jul 10.

Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, P.O.62511, Egypt.

The present study was led to investigate the defensive role of Terminalia laxiflora extract (TLE) on fipronil (FPN) induced hepatotoxicity and nephrotoxicity in male rats. Rats were administered with TLE (100 mg/kg) against the renal toxicity and hepatotoxicity induced by administration of FPN (10.5 mg/kg) for 30 days. At the end of the experimental period, the serum, liver, and kidneys were harvested and assessed for subsequent analysis. FPN administration to rats resulted in a significant elevation of serum transaminases, urea, and creatinine. Also, FPN-treated groups exhibited a marked reduction in total protein and albumin levels. Compared with the control group, the level of malondialdehyde (MDA) was elevated in groups treated with FPN, whereas superoxide dismutase (SOD), catalase (CAT) activities, and glutathione levels were distinctly reduced in this group. Significant increases in genomic DNA fragmentation and the expression level of the caspase-3 gene were also recorded. The biochemical result was supported by histopathological findings. Co-administration of TLE along with FPN significantly diminished the liver and kidney function tests decreased the level of lipid peroxidation, and enhanced all the antioxidant enzymes, while also diminishing the expression of caspase-3 and DNA laddering, indicating amelioration of DNA damage. These results indicate that TLE plays a vital role in diminishing FPN-induced hepatotoxicity and nephrotoxicity.
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http://dx.doi.org/10.1007/s11356-020-10018-5DOI Listing
November 2020

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

Int J Nanomedicine 2019 20;14:7729-7741. Epub 2019 Sep 20.

Department of Biochemistry, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

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.
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http://dx.doi.org/10.2147/IJN.S220572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855620PMC
March 2020

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

Acta Histochem 2019 Jul 6;121(5):563-574. Epub 2019 May 6.

Department of Biochemistry and Molecular Biology, Faculty of Vet. Med., Cairo University, Egypt. Electronic address:

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.
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http://dx.doi.org/10.1016/j.acthis.2019.04.005DOI Listing
July 2019

The modulates the neurotoxicity induced by fipronil in male albino rats.

Biosci Rep 2019 03 1;39(3). Epub 2019 Mar 1.

Department of Phytochemistry and Plant Systematics, National Research Center, Dokki, Giza, Egypt.

The extensive use of fipronil (FPN) may trigger hazards to more than insects. The present investigation was carried out to evaluate the abrogating role of (TL) methanol extract (TLE) against the neurotoxic effects provoked by FPN. Fourty male albino rats were assigned into four equal groups. The first group served as control, the second one was orally administered FPN (10.5 mg/kg BW), the third group was given combination of FPN and TLE) (100 mg/kg BW), and the fourth one was orally given TLE. Our findings highlighted the efficacy of TLE as a neuroprotectant through a significant reduction in malondialdehyde (MDA) content by 25.8%, elevations of the reduced glutathione (GSH) level, catalase (CAT,) and superoxide dismutase (SOD) activities by 30.9, 41.2, and 48.2% respectively. Consequently, the relative mRNA levels of both Bax and caspase-3 were down-regulated by 40.54% and caspase-3 by 30.35% compared with the control group. Moreover, restoration of the pathological tissue injuries were detected. In conclusion, TLE proved to be a potent neuroprotective agent against the FPN-induced toxicity.
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http://dx.doi.org/10.1042/BSR20181363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395302PMC
March 2019

Modulation of caspase-3 gene expression and protective effects of garlic and spirulina against CNS neurotoxicity induced by lead exposure in male rats.

Neurotoxicology 2019 05 28;72:15-28. Epub 2019 Jan 28.

Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Lead (Pb) is a ubiquitous environmental and industrial pollutant with worldwide health problems. The present study was designed to investigate the neurotoxic effects of Pb in albino rats and to evaluate the ameliorative role of garlic as well as Spirulina maxima against such toxic effects. Forty adult male rats were used in this investigation (10 rats/group). Group I: served as control, Group II: rats received lead acetate (100 mg/kg), Group III: rats received both lead acetate (100 mg/kg) and garlic (600 mg/kg) and Group IV: rats received both lead acetate (100 mg/kg) and spirulina (500 mg/kg) daily by oral gavage for one month. Exposure to Pb acetate adversely affected the measured acetyl cholinesterase enzyme activity, oxidative stress and lipid peroxidation parameters as well as caspase-3 gene expression in brain tissue (cerebrum and cerebellum). Light and electron microscopical examination of the cerebrum and cerebellum showed various lesions after exposure to Pb which were confirmed by immunohistochemistry. On the other hand, administration of garlic and spirulina concomitantly with lead acetate ameliorated most of the undesirable effects. It could be concluded that, the adverse effects induced by lead acetate, were markedly ameliorated by co-treatment with S. maxima more than garlic.
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http://dx.doi.org/10.1016/j.neuro.2019.01.006DOI Listing
May 2019

Genetic polymorphism in melatonin receptor 1A and arylalkylamine N-acetyltransferase and its impact on seasonal reproduction in Egyptian sheep breeds.

Arch Anim Breed 2018 20;61(4):505-516. Epub 2018 Dec 20.

Biotechnology Research Department, Animal Production Research Institute, Dokki, Egypt.

This study was carried out to detect polymorphisms in the melatonin receptor 1A (MTNR1A) and arylalkylamine N-acetyltransferase (AA-NAT) genes and their association with reproductive traits. Blood samples of 126 animals from three Egyptian sheep breeds were collected. DNA was extracted and subjected to PCR restriction fragment length polymorphism (RFLP) analysis using the RsaI and SmaI enzymes. Two alleles (C and T) and three genotypes (CC, CT and TT) for MTNR1A and for AA-NAT (A and G; GG, GA and AA) were detected. The alleles C and A and the genotypes CT and GA showed the highest frequencies for the MTNR1A and AA-NAT genes, respectively. Association analysis of the MTNR1A single nucleotide polymorphism (SNP) with ewe reproductive traits revealed significant associations in the Ossimi and Rahmani breeds with age at first lambing, and the C allele seemed to be the favorable allele. The results for the AA-NAT SNP demonstrated significant correlations in Ossimi with age at first lambing and litter size and in Rahmani with lambing interval; the G allele seemed to be the desirable allele. In the first conception season, ewes carrying CT exhibited a significantly lower age of first lambing in the unfavorable season. Additionally, GG ewes exhibited a significantly lower age of first lambing in the early favorable season, followed by the unfavorable season. To the best of our knowledge, this is the first study of these associations in Egyptian sheep breeds. In conclusion, the polymorphisms revealed in this study could be used as genetic markers to improve reproductive efficiency during the unfavorable season, and the obtained desirable genotypes could be considered in new genetic selection schemes.
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http://dx.doi.org/10.5194/aab-61-505-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065383PMC
December 2018

Nano-sized selenium attenuates the developmental testicular toxicity induced by di-n-butyl phthalate in pre-pubertal male rats.

Biomed Pharmacother 2018 Nov 10;107:1754-1762. Epub 2018 Sep 10.

Biochemistry and Chemistry of Nutrition Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

The current study was conducted to test the possible ameliorative role of selenium nanoparticles (Se-NPs) against oxidative damage of Leyding cells induced by di-n-butyl phthalate (DBP) in pre-pubertal male rat offspring. Forty-two pregnant female rats treated from gestation day (GD) 12 to postnatal day (PND) 14 day with two doses of Se-NPs (0.2 and 0.5 mg/kg/d) against developmental testicular toxicity induced by DBP (500 mg/kg/d). At PND 25 serum and testes of offspring were collected. Serum LH, the Leydig cells performance [total serum testosterone, LH and testosterone (LH/T) ratio, relative gene expression of insulin-like growth factor-3 (INSL3) and mineralocorticoid receptor (MR)], oxidative stress biomarker malondialdehyde (MDA) and antioxidant machinery [reduced glutathione (GSH), and the relative gene expression of antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx)] were estimated in all groups. The obtained results revealed that maternal exposure to DBP significantly reduced total serum testosterone level, relative mRNA expression of INSL3 and MR genes with observed testicular damage revealed by increasing MDA and depressed levels of GSH and antioxidant enzymes. The histopathological changes include necrosis and desquamation of spermatogoneal cells. Co-administration of Se-NPs high dose along with DBP significantly increased serum testosterone, improved LH/T ratio and the relative mRNA expression of INSL3 and MR genes, decreased the level of MDA, and also improved all the antioxidant enzymes expression levels. In conclusion, Se-NPs could be a potent maternal prophylactic agent against the reduced total serum testosterone level and oxidative damage of Leydig cells induced by DBP via reducing the lipid peroxidation (LPO) and enhancing the antioxidant state in pre-pubertal male rat offspring.
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http://dx.doi.org/10.1016/j.biopha.2018.09.006DOI Listing
November 2018

Maternal exposure to di-n-butyl phthalate induces alterations of c-Myc gene, some apoptotic and growth related genes in pups' testes.

Toxicol Ind Health 2018 Nov 19;34(11):744-752. Epub 2018 Sep 19.

1 Biochemistry Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

The aim of this study was to investigate the effects of maternal exposure to di-( n-butyl) phthalate (DBP) on testicular development and function in pre-pubertal and post-pubertal male rat offspring. Fourteen pregnant female rats were equally divided into two groups: a control group and a DBP-treated group. During gestation day (GD) 12 to postnatal day (PND) 14, the control group was administered 1 ml/day corn oil, and the DBP-treated group was administered DBP 500 mg/kg/day by oral gavage. On PND 25 (pre-puberty) and PND 60 (post-puberty), blood for serum and the testes were collected from five male offspring of each group. To determine the relationship between the methylation state of the c-Myc promoter and the expression of the c-Myc gene, some apoptotic-related genes, such as p53 and Bax, the anti-apoptotic Bcl-2 gene, and some growth arrest-related genes, such as BRD7 and GAS1, were examined. Compared with the control ( p < 0.05), at pre-puberty, DBP induces c-Myc hyper-methylation with significant downregulation for c-Myc, p53, Bax genes, and significant upregulation for Bcl-2, BRD7, and GAS1, while at post puberty, the methylation state and expression of c-Myc and apoptosis-related genes returned to control levels in the same sequence with the fold change in the expression of BRD7 and GAS1 genes. These findings suggest that DBP induced a transient pre-pubertal increase in c-Myc promoter methylation that may be associated with disruption of both apoptotic and growth mechanisms in the testes.
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http://dx.doi.org/10.1177/0748233718791623DOI Listing
November 2018

Innovative perception on using Tiron to modulate the hepatotoxicity induced by titanium dioxide nanoparticles in male rats.

Biomed Pharmacother 2018 Jul 24;103:553-561. Epub 2018 Apr 24.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. Electronic address:

The extensive application of titanium dioxide nanoparticles (TiO NPs) in the food industry arouses a debate regarding the probable risk associated with their use. Several recent studies reported that most nanoparticles (NPs) have adverse actions on the liver. The objective of this study is to examine whether Tiron plays a modulatory role against apoptotic damage induced by TiO NPs in rat livers. Forty rats were randomly divided into 4 groups; a control group received phosphate-buffered saline, an intoxicated group received 100 mg/kg/day of TiO NPs for 60 days, a treated group received 470 mg/kg/day of Tiron for the last 14 days after TiO NPs administration, and a Tiron group received Tiron only as previously mentioned. Oral administration of TiO NPs significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). In the liver, TiO NPs increased oxidative stress through increasing lipid peroxidation and decreasing GSH concentration and the levels of the SOD and GPx enzymes. TiO NPs significantly upregulated the proapoptotic Bax gene and downregulated the antiapoptotic Bcl-2 gene. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Apoptotic lesions were also obvious in this group. Treatment with Tiron as an antioxidant significantly decreased serum biochemistry, ameliorated oxidative stress in hepatic tissue, upregulated Bcl-2, decreased Bax expression and attenuated the histopathology of hepatic injury. These findings indicate that Tiron effectively diminishes the hazardous effects of TiO NPs on rat liver.
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http://dx.doi.org/10.1016/j.biopha.2018.04.064DOI Listing
July 2018

Hepatoprotective influence of quercetin and ellagic acid on thioacetamide-induced hepatotoxicity in rats.

Can J Physiol Pharmacol 2018 Jun 7;96(6):624-629. Epub 2018 Feb 7.

b Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Despite all the studies performed to date, therapy choices for liver injuries are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. Quercetin (QR) and ellagic acid (EA) had potent antioxidant and anti-inflammatory activities. The current study aimed at evaluating the potential hepatoprotective influence of QR and EA against thioacetamide (TAA)-induced liver toxicity in rats and the underlying mechanism using silymarin as a reference drug. Fifty mature male rats were orally treated daily with EA and QR in separate groups for 45 consecutive days, and then were injected with TAA twice with 24 h intervals in the last 2 days of the experiment. Administration of TAA resulted in marked elevation of liver indices, alteration in oxidative stress parameters, and significant elevation in expression level of fibrosis-related genes (MMP9 and MMP2). Administration of QR and EA significantly attenuated the hepatic toxicity through reduction of liver biomarkers, improving the redox status of the tissue, as well as hampering the expression level of fibrosis-related genes. In this study, QR and EA were proved to attenuate the hepatotoxicity through their antioxidant, metal-chelating capacity, and anti-inflammatory effects.
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http://dx.doi.org/10.1139/cjpp-2017-0651DOI Listing
June 2018

Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.

Biomed Pharmacother 2017 Sep 12;93:779-787. Epub 2017 Jul 12.

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biopha.2017.07.006DOI Listing
September 2017

Biochemical and histological studies on adverse effects of mobile phone radiation on rat's brain.

J Chem Neuroanat 2016 12 26;78:10-19. Epub 2016 Jul 26.

Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Egypt. Electronic address:

With the rapid development of electronic technologies, the public concern about the potential health hazards induced by radiofrequency (RF) radiation has been grown. To investigate the effect of 1800MHz RF radiation emitted from mobile phone on the rat's brain, the present study was performed. Forty male rats were randomly divided into two equal groups; control and exposed group. The later one exposed to 1800MHz emitted from mobile phone with an SAR value of 0.6W/kg for two hours/day for three months. The brain tissues were collected at the end of the experimental period and separated into hippocampus and cerebellum for subsequent biochemical, histological, immunohistochemical and electron microscopic investigations. The rats that were exposed to RF- radiation had a significant elevation in MDA content and a significant reduction in antioxidant parameters (glutathione, super oxide dismutase and glutathione peroxidase) in both regions. Degenerative changes were observed in the hippocampus pyramidal cells, dark cells and cerebellar Purkinje cells with vascular congestion. In addition a significant DNA fragmentation and over expression of cyclooxygenase-2 apoptotic gene was detected. Those results suggested that, direct chronic exposure to mobile phone caused severe biochemical and histopathological changes in the brain.
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http://dx.doi.org/10.1016/j.jchemneu.2016.07.009DOI Listing
December 2016

Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats.

Nanoscale Res Lett 2015 Dec 16;10(1):363. Epub 2015 Sep 16.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.
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http://dx.doi.org/10.1186/s11671-015-1068-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573085PMC
December 2015

Influence of green tea extract on oxidative damage and apoptosis induced by deltamethrin in rat brain.

Neurotoxicol Teratol 2015 Jul-Aug;50:23-31. Epub 2015 May 23.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. Electronic address:

In the present study, we investigated the protective effect of an aqueous extract of green tea leaves (GTE) against neurotoxicity and oxidative damage induced by deltamethrin (DM) in male rats. Four different groups of rats were used: the 1st group was the vehicle treated control group, the 2nd group received DM (0.6 mg/kg BW), the 3rd group received DM plus GTE, and the 4th received GTE alone (25 mg/kg BW). The brain tissues were collected at the end of the experimental regimen for subsequent investigation. Rats that were given DM had a highly significant elevation in MDA content, nitric oxide concentration, DNA fragmentation and expression level of apoptotic genes, TP53 and COX2. Additionally, a significant reduction in the total antioxidant capacity in the second group was detected. The findings for the 3rd group highlight the efficacy of GTE as a neuro-protectant in DM-induced neurotoxicity through improving the oxidative status and DNA fragmentation as well as suppressing the expression of the TP53 and COX2 genes. In conclusion, GTE, at a concentration of 25mg/kg/day, protected against DM-induced neurotoxicity through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product against DM-induced neurotoxicity.
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http://dx.doi.org/10.1016/j.ntt.2015.05.005DOI Listing
April 2016

Vitamin E attenuates neurotoxicity induced by deltamethrin in rats.

BMC Complement Altern Med 2014 Dec 2;14:458. Epub 2014 Dec 2.

Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.

Background: The safety of Deltamethrin (DM) has been raised as a point of concern. The current investigation was envisaged to explore the responsiveness of oxidative stress parameters, DNA fragmentation and expression levels of TP53, cycloxygenase 2 (COX2) and cytochrome p4502E1 (CYP2E1) as toxicological endpoint in rats treated with DM. as well as attention was provided to the neuroprotective effect of vitamin E (VE).

Methods: Four different groups of rats were used in this study, group I served as control, group II received DM (0.6 mg/kg BW), group III received both DM plus VE and finally group IV received VE only (200 mg/kg BW). The treatment regimen was extending for one month for all groups and the brain tissues were collected for further analysis.

Results: The obtained results showed a highly statistically significant increase in lipid peroxidation (LPO) content, nitric oxide concentration, and DNA fragmentation percentage and expression level of CYP2E1, TP53 and COX2 genes, in addition statistical significant reduction in total antioxidant capacity in DM treated group as compared to control were detected. Oral administration of VE attenuated the neurotoxic effects of DM through improvement of oxidative status, DNA fragmentation percentage and suppressing the expression level of CYP2E1, TP53 and COX2 genes.

Conclusion: From this study we concluded that VE supplementation has beneficial impacts on DM neurotoxicity in rats through its antioxidant and antiapoptotic properties.
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http://dx.doi.org/10.1186/1472-6882-14-458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265463PMC
December 2014
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