Nesreen Moustafa Omar

Nigella sativa oil alleviates ultrastructural alterations induced by tramadol in rat motor cerebral cortex

Tramadol is an opioid analgesic used to alleviate acute and chronic pain. Nigella sativa oil is one of the traditional remedies with antioxidant activity. This study was designed in order to investigate the ultrastructural alterations induced by tramadol in the rat cerebral cortex and to find out any possible protective effect of N. sativa oil against these alterations. Twenty-four male albino rats were assigned to three groups. Group I received intraperitoneal and oral normal saline for 30 days. Group II received intraperitoneal injections of tramadol 20 mg/kg/day, 40 mg/kg/day and 80 mg/kg/day on the first, second and third 10 days of the study, respectively. Group III received intraperitoneal tramadol similar to Group II and oral N. sativa oil at a dose of 4 ml/kg/day for 30 days. Specimens from the motor area were obtained and processed for transmission electron microscopy. In the tramadol-treated group, pyramidal and granular cells appeared shrunken and showed ultrastructural features of apoptosis such as nuclear membrane invaginations, chromatin margination, dilated rough endoplasmic reticulum, dilated Golgi saccules, and mitochondria with disintegrated cristae. The myelinated axons showed disorganization and splitting of the myelin sheath and contained vacuoles and abnormal mitochondria. Administration of N. sativa oil partially protected the cortical neurons and myelinated axons against tramadol-induced changes. In conclusion, N. sativa oil alleviates ultrastructural apoptotic changes induced by tramadol in the rat motor cerebral cortex.

An immunohistochemical and ultrastructural analysis of the retina in tadalafil (Cialis) treated rats

Tadalafil (Cialis) is one of the most commonly used phosphodiesterase type5 (PDE5) inhibitors. This work aimed to analyze the histological and ultrastructural changes provoked by chronic tadalafil administration in the rat retina, correlate between such changes and PDE5 immunoexpression and to evaluate the possible reversibility of these changes. Thirty Sprague Dawley male rats were randomly distributed into 3 groups. Control group; given 1 ml distilled water daily for 6 weeks. Tadalafil group; given tadalafil in a daily dose of 2.6 mg/kg for 6 weeks. Withdrawal group; given tadalafil 2.6 mg/kg daily for 6 week followed by a withdrawal period of 4 weeks. Retinal specimens were prepared for histological, ultrastructural and immunohistochemical study using anti-PDE5 and anti-Bcl-2 antibodies. Morphometric and statistical studies were performed. Tadalafil group displayed a significant reduction in retinal thickness, diminished cell population of outer and inner nuclear layers, dilated blood capillaries and a significant decline in the number of ganglion cells. Significant reductions of both PDE5 and Bcl-2 immunoexpression were observed. At the ultrastructural level, the photoreceptors showed spacing of outer segments and disorganized membranous discs. Retinal neurons showed ultrastructural degenerative changes in the form of shrunken irregular nuclei, dilated rER, and disrupted mitochondria. Withdrawal group revealed preservation of histological structure and partial restoration of retinal thickness, retinal cells ultrastructure, and PDE5 and Bcl-2 immunoexpressions. In conclusion, chronic use of tadalafil could induce reversible apoptotic and degenerative changes in retinal neurons due to its inhibitory effect on PDE5 expression which affects the metabolism and viability of retinal cells.

The impact of black seed oil on tramadol-induced hepatotoxicity: Immunohistochemical and ultrastructural study

The natural herb, black seed (Nigella Sativa; NS) is one of the most important elements of folk medicine. The aim was to evaluate the impact of Nigella Sativa Oil (NSO) on the changes induced by tramadol in rat liver. Twenty four albino rats were used. CONTROL GROUP given intraperitoneal and oral saline for 30days. TR-group: given intraperitoneal tramadol (20, 40, 80mg/kg/day) in the first, middle and last 10days of the experiment, respectively. TR+NS group: administered intraperitoneal tramadol in similar doses to TR-group plus oral NSO (4ml/kg/day) for 30days. Immunohistochemical, electron microscopic, biochemical and statistical studies were performed. TR-group displayed disarranged hepatic architecture, hepatic congestion, hemorrhage and necrosis. Apoptotic hepatocytes, mononuclear cellular infiltration and a significant increase in the number of anti-CD68 positive cells were observed. Ultrastructurally, hepatocytes showed shrunken nuclei, swollen mitochondria, many lysosomes and autophagic vacuoles. Activated Ito and Von Kupffer cells were also demonstrated. Elevated serum levels of AST, ALT, ALP and bilirubin were noticed. NSO administration resulted in preservation of hepatic histoarchitecture and ultrastructure and significant reductions in the number of anti-CD68 positive cells and serum levels of liver seromarkers. In conclusion, NSO administration could mitigate the alterations induced by tramadol in rat liver.

The possible protective role of pumpkin seed oil in an animal model of acid aspiration pneumonia: Light and electron microscopic study

Aspiration pneumonitis is a common problem occurring in many clinical disorders. Pumpkin seed oil (PO) is a rich source of antioxidants. This work aimed to assess the effect of PO on the lung histopathological changes induced by acid aspiration. Forty male albino rats assigned to four groups were used. Rats of control group were instilled intratracheally with normal saline 2mL/kg. HCL group instilled with 2mL/kg of HCL 0.1N, pH 1.25. PO group received pumpkin seed oil (PO) orally (∼1375mg/kgbw/day) for 7days. HCL+PO group instilled with 2mL/kg of HCL 0.1N, pH 1.25 and received PO at the same dose of PO group. Lung tissue samples were processed for light, electron microscopic and immunohistochemical study using anti inducible NO synthase (iNOS). The lung of HCL group demonstrated thickened interalveolar septa, inflammatory cell infiltration and significant increase in the area percent of collagenous fibers and immune expression of iNOS. Ultra structurally, disrupted alveolocapillay membrane, degenerated type II pneumocytes and plentiful alveolar macrophages were evident. PO administration partially attenuated these histological and ultra structural alterations and reduced iNOS immune-expression in lung tissue. In conclusion, PO has a protective effect against HCL aspiration lung injury most probably through its antioxidant activity.

Identification of Cyclase-Associated Protein-2 as a Novel Biomarker for Early-Stage Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is an aggressive deadly cancer with few therapeutic options mostly limited for early-stage HCC. Unfortunately, alphafetoprotein (AFP) has a limited performance, especially in early-stage HCC. Objectives: to investigate plasma levels of Cyclaseassociated protein-2 (CAP2) as a new biomarker and evaluate its role in detecting early-stage and AFP-negative HCC Egyptian patients. Methods: Plasma CAP2 and AFP levels in 150 HCC, 150 cirrhotic patients, 150 healthy controls. Correlation with tumor behavior, the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy were analyzed. Results: Plasma CAP2 and AFP levels were significantly elevated in HCC patients than liver cirrhosis and controls. Only plasma CAP2 levels significantly correlated with clinico-pathological characteristics of HCC (BCLC, histological and clinical stages) but not correlated with patients age, gender, viral infection status or AFP levels. Compared to AFP, CAP2 had significantly higher AUC: 0.86 (0.79-0.93) vs. 0.75 (0.65-0.85), Sensitivity: 81.5% vs. 62% in all HCCs and significantly higher AUC: 0.80 (0.72-0.89) vs. 0.68 (0.58-0.79, Sensitivity: 80.5% vs. 43.1% in earlystage HCC. Moreover, the combined diagnostic value of both CAP2+AFP was statistically significantly better than either CAP2 or AFP alone. Also, CAP2 could predict 82.4% of AFP-negative HCCs [AUC: 0.85 (0.77-0.92)] and 73.5% of AFP-negative early-stage HCCs [AUC: 0.80 (0.72-0.88)]. Conclusion: Compared with AFP, CAP2 was significantly elevated in HCC patients with higher sensitivity and AUC especially for early-stage HCC. Moreover, CAP2 was significantly correlated with the clinico-pathological features of HCC. CAP2 could be a novel biomarker predicting early-stage, AFP-negative, and AFP-negative early-stage HCC patients.

The possible ameliorating effect of Nigella sativa oil on tramadol-induced apoptosis in the motor area of rat cerebral cortex: a histological and immunohistochemical study

Background Tramadol is a centrally active analgesic commonly prescribed for moderate to severe pain. Thymoquinone, the major active component of the Nigella sativa oil, is characterized by its antioxidant properties. Aim of the work This study aimed to demonstrate the histological and p53-immunohistochemical changes induced by tramadol in the rat cerebral cortex and evaluate the potential role of N. sativa oil in the attenuation of these changes. Materials and methods Twenty-four male albino rats divided into three groups were used in this study. Group I was the control group. Group II was given repeated intraperitoneal injections of increasing doses of tramadol of 20, 40, and 80 mg/kg/day on the first, second, and third ten days of the study, respectively. Group III was given oral N. sativa oil 4 ml/kg/day, 30 min before each tramadol injection for 30 days. Paraffin sections of the frontal cortex motor area were prepared and stained with H&E and with an immunohistochemical stain using anti-p53 antibody. Results In group II rats, numerous shrunken pyramidal cells with acidophilic cytoplasm and deeply stained pyknotic nuclei were seen. Some of the granular cells appeared as ghosts with margination of chromatin. Homogeneous acidophilic masses containing fragmented deeply stained nuclei and surrounded by clear halos were also observed. The number of p53-positive cells was significantly higher compared with both group I and group III. In contrast, in group III, multiple pyramidal and granular cells appeared normal and the number of p53-positive cells was significantly less compared with group II. Conclusion N. sativa oil and derived thymoquinone ameliorate tramadol-induced apoptosis in the motor area of the rat cerebral cortex.

Immunohistochemical localization of epidermal growth factor receptors in the liver of normal and streptozotocin-induced diabetic rats

Background Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which affects different tissues including the liver. Epidermal growth factor receptor (EGFR) family is one of the tyrosine kinase receptor families that regulate liver pathophysiology. Aim of the work This study aimed to demonstrate the histological and EGFR immunohistochemical changes that occur in the liver of streptozotocin (STZ)-induced diabetic rat. Materials and methods Twenty male albino rats divided into two groups, group I (control) and group II (diabetic), were used. Diabetes was induced in the animals in group II by a single intraperitoneal injection of STZ (40 mg/kg). Five rats from each group were sacrificed 2 and 4 weeks after the STZ injection. Blood samples were collected for detection of serum glucose and insulin levels. Paraffin sections of the liver were prepared and stained with H&E, periodic acid Schiff, Masson’s trichrome stains, and immunohistochemical stain using anti-EGFR antibody. Results Diabetes mellitus was associated with marked congestion of central veins, blood sinusoids, and hepatic veins. Hepatocytes showed degenerative and fatty changes, especially in the periportal regions. Four weeks after induction of diabetes, signs of hepatic regeneration such as large binucleated hepatocytes were observed in the pericentral regions. Control livers showed strong positive EGFR immunoreactivity in hepatocytes, mainly in the periportal and pericentral regions, and in the bile duct epithelium. A marked decrease in EGFR immunoreactivity was observed in the livers of diabetic rats. Conclusion Diabetes mellitus is associated with marked hepatic congestion, degenerative and fatty changes in the hepatocytes, and decreased hepatic EGFR immunoreactivity.