Zaki, S. M., S. A. Fattah, and D. S. Hassan, "The differential effects of high-fat and high- -fructose diets on the liver of male albino rat and the proposed underlying mechanisms.", Folia morphologica, vol. 78, issue 1, pp. 124-136, 2019. Abstract

BACKGROUND: The Western-style diet is characterised by the high intake of energy- -dense foods. Consumption of either high-fructose diet or saturated fat resulted in the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Many researchers studied the effect of high-fat diet (HFD), high-fructose diet (HFruD) and high-fructose high-fat diet (HFHF) on the liver. The missing data are the comparison effect of these groups i.e. are effects of the HFHF diet on the liver more pronounced? So, this study was designed to compare the metabolic and histopathological effect of the HFD, HFruD, and HFHF on the liver. The proposed underlying mechanisms involved in these changes were also studied.

MATERIALS AND METHODS: Twenty four rats were divided into four groups: con- trol, HFD, HFruD, and HFHF. Food was offered for 6 weeks. Biochemical, light microscopic, immunohistochemical (Inducible nitric oxide synthase [iNOS] and alpha-smooth muscle actin [α-SMA]), real-time polymerase chain reaction (gene expression of TNF-α, interleukin-6, Bax, BCL-2, and caspase 3), histomorphometric analysis and oxidative/antioxidative markers (thiobarbituric acid reactive substances [TBARS], malondialdehyde [MDA]/glutathione [GSH] and superoxide dismutase [SOD]) were done.

RESULTS: The HFD, HFruD and HFHF groups developed a cluster of liver disorders; steatosis, necrosis, inflammation, apoptosis, ballooning degeneration and cytopla- smic vacuolations. Internal metabolic impairments include elevated serum levels of glucose, triglycerides, low density lipoprotein and decreased serum levels of high density lipoprotein and albumin. The immunoreaction of the α-SMA and iNOS was strong in these groups. The oxidant markers (MDA and TBARS) were elevated, while the antioxidant markers (SOD and GSH) were decreased. The area per cent of collagen, inflammatory markers, caspase 3 and Bax were elevated, while the BCL-2/Bax ratio was decreased. The decrease in PAS, antioxidant markers and the elevation of the α-SMA, iNOS, inflammatory and oxidant markers were obvious in the HFHF when compared to that of the other groups.

CONCLUSIONS: High-fat diet, HFruD, and HFHF developed morphologic hepatic changes ranging from steatosis to necrosis and inflammation, besides the deve- lopment of internal metabolic impairments. The chief factors of hepatic injury were fat accumulation in the hepatocytes, oxidative stress and highly elevated iNOS. Compared to the other groups, HFHF's effect was more prominent.

Zaki, S. M., W. A. Abd Al Galeel, R. A. N. Imam, G. F. Soliman, and F. M. Ghoneim, "Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage.", Histochemistry and cell biology, 2020. Abstract

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.

Zaki, S. M., A. H. K. Abdelmaksoud, B. E. A. Khaled, and I. A. Abdel Kader, "Anatomical variations of hepatic artery using the multidetector CT angiography.", Folia morphologica, 2019. Abstract

BACKGROUND: the frequency of normal and aberrant hepatic arteries differs among ethnicities. The aim of our work was to study the frequency of normal and aberrant hepatic arteries among Egyptian using multidetector CT (MDCT) and to compare our prevalence with the prevalence of other nationalities. In addition, the gender differences of such variations were clarified. In addition, the arterial feeding of hepatic segment IV was determined.

MATERIALS AND METHODS: The present study was carried out on 500 patients (409 males and 91 females). Abdominal CT was performed using two MDCT systems, a 64-row, and a 256-slice system.

RESULTS: According to Michel's classification, the normal anatomy (type I) was observed in 369 cases (73.8%), while anomalous hepatic arterial pattern was detected in 131 cases (26.2%).These anomalies were distributed as the following; type II in 36 cases (7.2%) , type III in 60 cases (12%), types IV and V in 5 cases for each (1% each) , type VI in 14 (2.8%) and types VIII & IX in a single case for each (0.2% each). Neither type VII nor type X was detected. Nine unclassified cases (1.8 %) were observed. According to Hiaat's classification, the anomalies were distributed as the following; type II in 41 cases (8.2%), type III in 74 cases (14.8 %), type IV in 6 (1.2 %), type V in a single case (0.2%) and type VI in 2 cases (0.4%). Finally, seven unclassified cases (1.4 %) were observed. Common hepatic artery (CHA) originated from celiac trunk in 98% (79.8% males and 18.2% females). It originated from the abdominal aorta in 0.4% and from the superior mesenteric artery (SMA) in 0.4%. It was absent in 1.2%. Right hepatic artery (RHA) originated from the CHA in 86.6% (69.8% males and 16.8 % females) and from the SMA in 13.2% (11.8% males and 1.4% females) and from the abdominal aorta in 0.2% (a single male case). Left hepatic artery (LHA) originated from the CHA in 91.2% and from the left gastric artery (LGA) in 8.8%. The most common origin of the segment IV blood supply was the LHA in 60.8%, followed by the RHA in 35%. Less commonly, blood supply derived from the hepatic artery proper (HAP) in 1%. Combined supply derived from RHA and LHA in 0.8%, from the LHA and HAP in 2% and the least encountered was from the RHA and HAP in 0.4%.

CONCLUSIONS: Hepatic artery variations among Egyptians have a different distribution when compared to such variations among other species. The normal hepatic arterial pattern was observed in 73.8%, while the anomalous was detected in 26.2%. The CHA originated from the celiac trunk in 98%, the RHA originated from the CHA in 86.6% and the LHA originated from the CHA in 91.2%. The most common arterial supply of the hepatic segment IV is derived from the LHA (60.2%).

Zaki, S. M., W. A. A. Algaleel, R. A. Imam, and M. M. Abdelmoaty, "Mesenchymal stem cells pretreated with platelet-rich plasma modulate doxorubicin-induced cardiotoxicity.", Human & experimental toxicology, vol. 38, issue 7, pp. 857-874, 2019. Abstract

The cardiotoxic adverse effect of doxorubicin (DOX) is the major factor limiting its use. Recently, mesenchymal stem cells (MSCs) have been implicated in the preclinical studies of treatment of DOX-induced cardiotoxicity. The question is MSCs pretreated with platelet-rich plasma (PRP) have a better influence on DOX-induced cardiotoxicity compared to the influence of MSCs alone. Twenty-four Wistar rats were categorized into control, DOX-treated, MSC-treated, and PRP/MSC-treated groups. DOX was injected for two consecutive weeks. Light microscopic, biochemical markers (interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and creatine kinase-MB (CK-MB)), immunohistochemical (Bax, Bcl2, vascular endothelial growth factor (VEGF), and cardiac troponin-I (CT-I)), and oxidative/antioxidative markers (malondialdehyde (MDA)/superoxide dismutase (SOD)) were measured. Degenerative cardiac changes were detected in the DOX-treated group with complete loss of the architecture and coagulative necrosis. These changes were accompanied with the elevation of the serum level of CK-MB and loss of CT-I immunoreactivity. The major factors in the DOX-induced cardiotoxicity were the oxidative stress (elevated MDA/decreased SOD), inflammation (elevated TNF-α/decreased IL-10), and cardiac apoptosis (lower Bcl2, higher Bax, and lower Bcl2/Bax ratio). MSCs and PRP/MSCs attenuate DOX-induced cardiotoxicity. Better attenuation was observed in the PRP/MSC-treated group. PRP/MSC combination reduced greatly the MDA and TNF-α and increased IL-10, Bcl2/Bax ratio, and VEGF. PRP had no significant influence over the Bcl2, Bax, and SOD. In conclusion, DOX in its toxic dose induced myocardial injury. This destructive effect is related to oxidative stress, inflammation, and cardiac apoptosis. PRP/MSC possesses a better attenuation over the DOX-induced toxicity compared to MSC alone.

Zaki, S. M., "Evaluation of antioxidant and anti-lipid peroxidation potentials of Nigella sativa and onion extract on nicotine-induced lung damage.", Folia morphologica, vol. 78, issue 3, pp. 554-563, 2019. Abstract

BACKGROUND: The present work aimed to compare the protective effect of Nigella sativa (NS) and onion extract on the nicotine-induced lung damage in rats. The antioxidant and anti-lipid peroxidation potentials of both agents on nicotine-induced lung damage were studied.

MATERIALS AND METHODS: Thirty-six Sprague-Dawley albino rats, treated for 18 weeks, were divided into six groups: one negative control group, two positive control groups (oral onion and oral NS), nicotine-treated group, onion extract-treated group (concomitant nicotine and onion extract) and NS-treated group (concomitant nicotine and NS oil). The assessment of lung structure was based on haematoxylin and eosin and transmission electron microscopy. Lung malondialdehyde (MDA), superoxide dismutase activity (SOD), catalase (CAT), lung glutathione (GSH), and epithelial lining fluid GSH (ELF GSH) were used for assessment of the antioxidant and anti-lipid peroxidation potentials of NS and onion extract.

RESULTS: The lung of the nicotine-treated group exhibited emphysematous air spaces, collapsed corrugated alveoli with ruptured interalveolar septa in some specimen and thickened septa in the others, massive congestion, extravasation of red blood cells, inflammatory cellular infiltration and fluid exudate. Much improvement was observed in the onion-treated group despite the presence of residual pathological affection. The lung in the NS-treated group showed the nearly normal architecture with slight congestion. Administration of nicotine promoted lipid peroxidation (elevation of MDA) and decreased the level of the antioxidant markers (SOD, CAT, lung GSH and ELF GSH). With the use of onion extract and NS, the level of MDA decreased by 17.85% and 35.71% while the levels of SOD, CAT, GSH, and ELF GSH increased. The increase was more prominent in the NS-treated group. The levels in the NS-treated group reached nearly the level markers of the control group.

CONCLUSIONS: Nigella sativa and onion extract attenuate the pathological effect of nicotine in the lung rats through antioxidative and anti-lipid peroxidative mechanisms with higher protection to NS.

Zaki, S. M., M. H. shaaban, W. A. Abd Al Galeel, and A. A. W. El Husseiny, "Configuration of the circle of Willis and its two parts among Egyptian: a magnetic resonance angiographic study.", Folia morphologica, 2019 Feb 14. Abstract

BACKGROUND: We hypothesized that the collateral circulation differs in different ethnic groups. So, the aim of our work was to study variations of the circle of Willis (COW) among Egyptian and to compare our findings with the findings of other nationalities.

MATERIAL AND METHODS: One hundred patients were studied using magnetic resonance angiographic (3D-TOF-MRA). Frequency and morphologic variations in COW were studied. The diameters of the arteries of the anterior and posterior circle were verified. Finally, the differences among the mean diameters of these arteries regarding age and sex were also studied.

RESULTS: Complete, partially complete and incomplete COW were encountered in 28%, 38% and 34% in the studied cases. The incomplete anterior circle was found in 34% (10 % isolated incomplete anterior circle and 24% combined incomplete anterior and posterior circles) and the incomplete posterior circle came across in 62% (38% isolated incomplete posterior circle and 24% combined incomplete anterior and posterior circles). Seven anterior circle variations were found. The commonest type was the classical type "a" with a prevalence of 56%, being higher in male (57.1%). The 2nd common type was type "g" (hypoplasia or aplasia of the anterior communicating artery) with a prevalence of 24 %, being higher in male (66.7%). Six posterior circle variations were found. The commonest variation was the classic type "a" with a prevalence of 26%, being higher in male (61.5%). Posterior circles types "d, e, h" (18%, 24%, 20%) constituted 62% and were characterized by hypoplasia/absent of the posterior communicating arteries.

CONCLUSIONS: The prevalence of complete COW (classic or textbook type) was encountered only 28% of the studied cases. Variations of COW were found to be more common in the posterior circulation (62%). The incomplete anterior circle was found in 34% and it is mostly caused by hypoplasia or aplasia of the anterior communicating artery which was found to be more common compared to the literature.

Zaki, S. M., E. A. Mohamed, A. G. Motawie, and S. Abdelfattah, "N-acetylcysteine versus progesterone on the cisplatin-induced peripheral neurotoxicity.", Folia morphologica, vol. 77, issue 2, pp. 234-245, 2018. Abstract

BACKGROUND: Cisplatin-induced peripheral nerve neurotoxicity (CIPN) is the main obstacle in cisplatin treatment. The aim of this study was to compare the modulatory effects of N-acetylcysteine (NAC) and progesterone on CIPN, because there are scarce literature data on the protective effect of the proge-sterone on the CIPN.

MATERIALS AND METHODS: Twenty-four rats were divided into four groups: control, cisplatin-treated, concomitant cisplatin-treated and NAC-treated, and concomitant cisplatin-treated and progesterone-treated. Electron microscopic, immunohistochemical, real time polymerase chain reaction and histomorphome-tric analysis; oxidative/antioxidative markers (MDA/GSH and SOD), neurotoxic/ neuroprotective markers (iNOS/nNOS), inflammatory mediators (TNF-a and NF-kB) and BAX were done.

RESULTS: The myelin sheath in the cisplatin-treated group elucidated infolding. The myelin was disfigured, degenerated, and extensively split with areas of focal loss. The axoplasm was atrophic. Ballooning and vacuolations of the mitochon-dria with alterations of Remak bundles structures were observed. Fewer of these changes were noted in the NAC and progesterone-treated groups. Decrease of the antioxidant SOD and GSH (81% and 64%) and increase of the oxidant MDA (9 folds), increment of the neurotoxic iNOS (1.9 folds) and decrement of the neuroprotective nNOS (64%) and elevation of the inflammatory mediators' TNF-a and NF-kB (8.3 and 11 folds) in the cisplatin-treated group. Increase of the antioxidant SOD (1.3 and 2.5 folds) and GSH (120% and 79%) and decrease of the oxidant MDA (69% and 88%), decrement of the neurotoxic iNOS (56% and 68%) and increment of the neuroprotective nNOS (1.6 and one folds) and elevation of the inflammatory mediators' TNF-a and NF-kB were observed in the NAC and progesterone-treated groups, respectively.

CONCLUSIONS: The toxic effect of CIPN might be attributed to either oxidative or severe inflammatory stress. Progesterone is efficient in ameliorating these effects; however, NAC is better. (Folia Morphol 2018; 77, 2: 234-245).

ZAKI, S. H. E. R. I. F. M., and K. EFFAT, "Evaluation of the Physical Growth in Egyptian Children with Phenylketonuria Under Diet Therapy", Med J Cai Univ, vol. 81, issue 2, pp. 107-112, 2013. Abstract53.pdf

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Zaki, S. M., E. A. Mohamed, S. A. Fattah, H. Abdullah, and L. Kaszubowska, "Age-associated functional morphology of thyroid and its impact on the expression of vimentin, cytokeratins and VEGF. The role of nigella in refinement.", Folia histochemica et cytobiologica, vol. 56, issue 3, pp. 159-171, 2018. Abstract

INTRODUCTION: Aging causes morphological and functional changes in the thyroid gland. Free radicals play a key role in the pathology of normal aging. Vimentin and cytokeratin are cytoskeletal intermediate filaments that are often used as indirect indices of tissue injury. The aim of the study was to clarify the age-related alterations in the structure and function of the thyroid gland. The relationship between oxidative/antioxidative stress markers and cytoskeletal intermediate filaments (vimentin and cytokeratin) and oxidative/antioxidative stress markers as well as vascular endothelial growth factor (VEGF) during aging were elucidated. Finally, the role of Nigella sativa (NS) oil in ameliorating age-related alterations of the structure and function of the thyroid gland was studied.

MATERIAL AND METHODS: Thirty Sprague-Dawley albino rats were divided into five groups: young adult control, young adult NS-treated, late adult control, late adult NS-treated, and senile. The age of young adult, late adult, and senile rats was nearly 7, 18 and 22 months, respectively. NS oil was added to food pellets and was administered at a daily dose of 0.1 g/kg body weight for one month. The thyroid gland was dissected and fixed immediately in 10% formalin saline. The assessment of thyroid structure was based on hematoxylin and eosin, and Masson's trichrome stainings, and histomorphometric analysis of the deparaffinized sections. Localization and distribution of vimentin and cytokeratin filaments was assessed by immunohistochemistry. Measurements of VEGF gene expression by qPCR and oxidative/antioxidative markers (malondialdehyde and glutathione content, superoxide dismutase activity) in thyroid gland homogenates were performed. Serum concentration of thyroid hormones (T3, T4) and TSH were assessed by radioimmunoassay.

RESULTS: Follicles in the late adult control group were dilated and disrupted. Follicular cells showed cytoplasmic vacuolation. Follicles in the thyroids of senile rats were of irregular shape, often with cellular exfoliations. Many follicles were dilated and lined with flattened cells. A notable amelioration of these morphological alterations was observed in late adult NS-treated rats. Decrease in serum T3 and T4 levels and increase in TSH levels were observed in the late adult control and senile groups. A clear shift of the oxidative/antioxidative markers (MDA/ /GSH, SOD) was observed in the late adult control and senile groups in favor of oxidants. Administration of NS to late adult rats resulted in normalization of these parameters. Increased area of collagen fibers, immunoreactivity of vimentin and cytokeratin filaments and VEGF gene expression were observed in the thyroids of late adult and senile rat groups as compared to young animals. The mean number of follicular cells decreased in the late adult control and senile groups. Administration of NS to the late adult rats returned these parameters to the level of the young adult rats.

CONCLUSIONS: Aging-related alterations in both structure and function of the rat thyroid gland that are associated with increased indices of oxidative stress might be abrogated by administration of antioxidative agents present in Nigella sativa oil.

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