Sally A. Selim

Neuroprotective effects of placenta-derived mesenchymal stromal cells in a rat model of experimental autoimmune encephalomyelitis.

BACKGROUND Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stromal cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS. A preparation of MSCs derived from full-term human placenta (PDMSCs) is a new approach in the treatment of patients with MS. OBJECTIVE This study aimed to rule out the possible therapy by PDMSCs in experimental autoimmune encephalomyelitis (EAE), a rat model of MS. METHODS AND RESULTS Thirty-five female Wistar rats were classified into the following groups: I, control; II, EAE untreated; III and IV, EAE treated with phosphate-buffered saline (PBS) at 9 and 16 days post-immunization (dpi), respectively; V and VI, EAE treated with PDMSCs at 9 and 16 dpi, respectively. Intravenous administration of PDMSCs at 9 or 16 dpi significantly ameliorated the disease course, decreasing brain inflammation and degenerating neurons. A reduction of axonal damage as well as an increase of oligodendrocyte precursors were recorded. Moreover, there was an engraftment of the PDMSCs into the brain tissue. Human brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin 3 (NTF3) were significantly expressed in brains of rats treated by PDMSCs. CONCLUSIONS Human PDMSCs have demonstrated striking therapeutic effects when delivered at the onset or at the peak of the disease. PDMSCs have direct neurotrophic support after their engraftment within the lesion through expression of the neurotrophins.

Differential effects of eugenol against hepatic inflammation and overall damage induced by ischemia/re-perfusion injury

Abstract Liver injuries, liver tumor resection, and liver transplantation are known to be responsible for ischemia/reperfusion (I/R) injury that, in turn, gives rise to liver damage. This study was undertaken to investigate the possible protective effect of eugenol against the damage induced by I/R in rat livers as well as to explore possible mechanisms of action. Male rats were divided into four groups: sham-operated, I/R only, and two groups that received 10 or 100 mg eugenol/kg/day (Eug10 and Eug100, respectively) for 15 days by gavage and were then subjected to I/R, i.e. an ischemia induced for 45 min followed by re-perfusion for 6 h. The rats were euthanized and liver tissues and blood collected for examination. The results showed that I/R induced massive hepatic structural and functional damage. Eug10-treated rats had improvement in both liver function and structure, and inhibition of I/R-induced increases in serum myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, as well as hepatic nuclear factor-κB (NF−κB) p65 and caspase-3 expression. Eug10 treatment also inhibited the degree of loss in reduced glutathione (GSH) and of rise in malondialdehyde (MDA) levels in liver tissues induced by I/R. In contrast, augmentation of liver damage induced by I/R was noted in Eug100-treated rats, with these hosts displaying significant increases in oxidant, inflammatory, and apoptotic markers relative to levels seen in I/R-only rats. The results of the present study provide the first evidence that a low dose of eugenol may protect the liver against I/R injury in part by decreasing levels of lipid peroxidation, down-regulating inflammatory mediators, and inhibiting apoptosis, and that a larger dose amplifies the liver injury via oxidant and inflammatory effects.

Effect of streptozotocin-induced diabetes mellitus on the cerebellar cortex of adult male albino rats: histological and immunohistochemical study

Introduction Diabetes mellitus is a common metabolic disorder with well-known serious secondary complications. It is also associated with central nervous system damage. This damage is characterized by impairment in brain functions, with neurochemical and structural abnormalities. Aim of the work To clarify the effects of streptozotocin-induced diabetes on the histological structure of the cerebellar cortex of adult rats. Materials and methods Twenty adult male albino rats were used in this study, randomly divided into three groups. Group I was the control group; group II received a single intraperitoneal injection of 0.1 ml saline; and group III received a single intraperitoneal injection of streptozotocin at a dose of 60 mg/kg freshly dissolved in 0.1 ml saline. After 8 weeks, the cerebellum was dissected and processed for light and electron microscopic examinations and also for glial fibrillary acidic protein (GFAP) to demonstrate the astrocytes. Morphometrical and statistical analyses were carried out. Results In group III, degenerative changes were observed in neurons. Mitochondrial alterations and disarrangement of myelin sheaths with increased area of myelinated axons were observed. Dispersed presynaptic vesicles in swollen axonal terminals were also observed. However, there was good evidence of gliosis, which was supported by a significant increase in the number of GFAP astrocytes. Conclusion The cerebellar cortex was particularly susceptible to hyperglycemia-induced oxidative stress and could have contributed toward the neuronal damage and increased astrocyte activity.

An experimental study of a rat model of emphysema induced by cigarette smoke exposure and the effect of Survanta therapy

The present study was performed to test the therapeutic effects of Survanta (an exogenous surfactant) on a Wistar rat model of emphysema. Thirty-five adult male Wistar rats were divided randomly into the following groups; control subgroups Ia&b (n=14); emphysematous model subgroups IIa,b&c (n=21) exposed to cigarette smoke (CS), received phosphate buffer solution (PBS) and Survanta respectively. The levels of serum myeloperoxidase (MPO), lung tissue lactate dehydrogenase (LDH), alkaline phosphatase (ALP) as well as antioxidants: catalase (CAT), superoxide dismutase (SOD) and oxidative stress: malondialdehyde (MDA) markers were measured. Immunohistochemical staining of the lung was applied with anti-P53, anti- tumor necrosis factor (TNFα) and anti-proliferating cell nuclear antigen (PCNA) to reveal the changes of the lung structure. The mean linear intercepts (MLI) of alveoli were measured to assess alveolar size. In emphysematous rats, the serum level of MPO and tissue LDH, ALP & MDA were significantly increased while; CAT and SOD were significantly decreased. Pictures analysis for all immunostains was clearly increased. In Survanta treated group, a significant improvement in all previously mentioned findings while; no improvement in alveolar diameter was detected. These results conclusively demonstrate that Survanta administration improves the inflammatory biochemical and histochemical parameters of the emphysematous lung.

Therapeutic effect of spermatogonial stem cell on testicular damage caused by lead in rats.

OBJECTIVE To investigate the possible therapeutic effect of spermatogonial stem cells (SSCs) on lead-induced apoptosis and consequently infertility in adult male rats. MATERIALS AND METHODS Sixty-six Sprague Dawley adult male rats were divided into three groups: control group, lead (Pb) acetate exposed group received (20mg Pb/kg) for 3weeks, and SSCs treated group. Each group included twenty-two rats. Serum testosterone level, 3 beta-hydroxysteroid dehydrogenase (3β-HSD), 17 beta-hydroxysteroid dehydrogenase (17β-HSD), proliferating cell nuclear antigen (PCNA) genes expression by RT-PCR, caspase 3 expression by immunohistochemistry and testicular histological findings were tested. RESULTS Pb acetate exposed rats showed a significant decrease in the epididymal sperm count, motility, viability, serum testosterone level and testicular expression of 3β-HSD, 17β-HSD and PCNA compared to the control group, while treatment with SSCs attenuated Pb acetate induced decrease for these variables. Moreover, the increasing apoptosis of germinal cells as well as the high expression of caspase-3 induced by Pb acetate was reduced by SSCs treatment. CONCLUSION SSCs exhibited therapeutic effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.

The effect of high-fat diet-induced obesity on the parotid gland of adult male albino rats: histological and immunohistochemical study

Introduction Obesity is a major health problem that affects up to 30% of adult and has been linked to an increase in dietary intake, especially fat intake and a sedentary lifestyle. In addition, it is a well-known aggravating factor in the pathology of many organs. Aim of the work The aim of the study was to investigate the histological and immunohistochemical changes in the parotid gland of the rats maintained on rich-fat diet. Materials and methods Sixteen adult male albino rats were divided equally into a control group I and a high-fat diet group II. Rats in group II were fed a high-fat diet for 3 months. At the end of the experimental period, blood samples were collected for detection of total cholesterol and triglyceride. Half of the parotid samples were processed for light microscopic examination, whereas the other half were prepared for electron microscopic examination. Paraffin sections were stained with H&E, Mallory trichrome, and also with &agr; smooth muscle actin (&agr;-SMA). Results Specimens from group II showed disarrangement of the acinar cells, cytoplasmic vacuolization, and nuclear irregularity. Marked fibrosis between serous acini and intense cellular infiltration were observed. An apparent increase in the immunoreaction for &agr;-SMA was found at the periphery of the acini and interlobular ducts. Conclusion The results of the present study suggest that there is a significant relationship between fat-rich diet intake and structural changes in the parotid gland, such as massive fibrosis, numerous dilated blood vessels, and intracellular vacuolization with lipid droplets.

Harmful effects of arsenic on the cerebral cortex of adult male albino rats: light and electron microscopic studies

IntroductionArsenic is a common environmental contaminant that is available worldwide. It has been reported that human arsenic exposure causes nervous system disturbances such as polyneuropathy and neurobehavioral deficits. Aim of the workThe purpose of this work was to describe the histological changes induced by arsenic in the cerebral cortex of adult male albino rats and discuss its possible mechanisms of action. Materials and methodsTwenty adult male albino rats were equally classified into control (I) and experimental (II) groups of 10 animals each. Rats of group II were intraperitoneally injected with 2mg/kg/day of sodium arsenite for 20 days. Samples from the temporal lobes of the cerebrum were taken and processed for light and electron microscopic examination. ResultsFeatures of neurodegeneration such as shrunken, irregular, and darkly stained nuclei and degenerating organelles were observed in arsenic-treated rats. Good evidence of gliosis and disrupted blood–brain barrier were also detected. ConclusionThe adult brain is particularly susceptible to arsenic-induced oxidative stress and contributes to the neurodegenerative lesions.

Renal corpuscle alterations induced by gentamicin in adult male albino rats and a possible protective role of ginger: histological and biochemical study

Introduction Gentamicin is a widely used effective antibiotic with a possible risk of nephrotoxicity. Ginger is an antioxidant that could play a protective role in models of experimentally induced nephropathies. Aim of the work The aim of this work was to study the possible histological and biochemical changes induced by gentamicin on renal corpuscles and evaluate the possible protective effect of ginger on gentamicin-induced renal damage in adult male albino rats. Materials and methods Twenty-four adult male albino rats divided into four groups (six rats each) were used in this study. Group I served as the control group. Rats of group II received only an aqueous extract of ginger at a daily dose of 1 ml for 7 days through a gastric tube. Rats of group III were injected intraperitoneally with gentamicin sulphate at a daily dose of 80 mg/kg for 7 days. Rats of group IV were given both ginger and gentamicin at the same doses and through the same routes as the previous two groups. At the end of the experiment, the rats were sacrificed after ether inhalation and blood samples were subjected to chemical assay for assessment of blood urea nitrogen (BUN), creatinine, superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Renal tissue samples were processed for light and electron microscopic examination. An immunohistochemical study was also performed for assessing &agr;-smooth muscle actin to demonstrate mesangial expansion. The obtained results were analysed morphometrically and statistically. Results Gentamicin caused several focal glomerular changes in the form of congestion and rupture of capillaries and also atrophic changes. Mesangial hyper-cellularity and increased inter-capillaries mesangial matrix were observed. Destroyed blood renal barrier was observed ultrastructurally. There was a highly significant increase in serum urea, creatinine and MDA, whereas SOD decreased. Ginger normalized the gentamicin-induced increase in serum BUN, creatinine, MDA and SOD. This was also evidenced by histological studies. Conclusion Gentamicin induced injurious effects on renal corpuscles. Coadministration of ginger during gentamicin treatment can ameliorate both the functional and histological changes induced by gentamicin.

Effect of perinatal acrylamide exposure on the liver of albino rat offspring: light and electron microscopic study

Introduction Acrylamide is an important and common chemical substance widely used for many industrial and laboratory purposes. Aim of the work This study was designed to determine the histological changes in developing rat liver following the administration of acrylamide in pregnant rats. Materials and methods Twenty-four pregnant female rats were administered acrylamide by gastric intubation at a dose of 10 mg/kg/day. Their offspring were divided into three groups: group I (control group) offspring of mothers were given saline; group II (IIa and IIb) offspring of mothers were given acrylamide at day 7 (D7) of gestation till D7 and D21, respectively, after birth; and group III (recovery group) offspring of mothers were treated with acrylamide from day D7 of gestation until D21 after birth and left for 1 month for recovery. Results The acrylamide-treated group IIa and IIb showed loss of hepatic architecture, areas of necrosis, bile ductular proliferation, and cellular infiltration. The hepatocytes had shrunken, deeply stained nuclei and a vacuolated cytoplasm. Depletion of glycogen granules with a decrease in nuclear DNA-containing particles was also observed. Ultrastructurally, rarification of the cytoplasm, vacuoles, and hemorrhage were observed. Ito cells abnormally lost their fat droplets with deposition of collagen fibers. The recovery group showed signs of improvement, where most of the hepatocytes almost retained their normal ultrastructure. Conclusion Acrylamide affects the liver of the developing rat during gestation and lactation periods. A recovery period was recommended to allow the tissues to retain their morphological and structural appearance.

Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling

Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the role of Nrf2 activation in modulating the response to sepsis following BMSCs treatment. Twenty-four adult male albino rats were assigned to: control, lipopolysaccharide (LPS) and LPS-stem cell groups. Liver samples were processed for light and electron microscope examinations. Immunohistochemical localization of BAX, proliferating cell nuclear antigen and nuclear factor-erythroid 2-related factor 2 (Nrf2) was carried out. Liver homogenates were prepared for assessment of reduced glutathione, glutathione peroxidase, tumor necrosis factor-alpha and interleukin-6 and also real-time PCR analysis of Nrf2 expression. BMSCs treatment improved the histopathological changes of the liver, enhanced tissue regeneration and decreased apoptosis following sepsis. We reported highly significant enhancement in Nrf2 expressions at mRNA and protein levels in the LPS-stem cell group compared with the LPS group. The up regulation of Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress induced by sepsis. Thus, BMSCs therapies could be a viable approach to treat sepsis-induced liver damage by activating Nrf2 signaling.