Protective effects of evening primrose oil on behavioral activities, nigral microglia and histopathological changes in a rat model of rotenone-induced parkinsonism.

Parkinson's disease (PD) is a neurodegenerative illness described as damage to dopaminergic neurons. There is increasing evidence that neuroinflammatory activity mediated by microglia is extensively involved in the initiation and development of PD. This study assessed the protective effect of evening primrose oil [EPO] as an anti-inflammatory mediator in rotenone-induced Parkinsonism in rats. Forty-eight adult male albino rats were distributed into four groups. Group I: control. Group II: rotenone [1.5 mg/kg/48 h] was administered subcutaneously to the rats. Groups III and IV: the rats had rotenone plus daily oral [EPO] 5 and 10 mg/kg respectively. After 24 days, motor behaviour was assessed by the open field and rotarod tests. The brain striata were isolated and tested for tumor necrosis factor (TNF)-α, interleukin 6, NF-B [nuclear factor-kappa B], and dopamine levels. The mid-brain tissues were processed for light and electron microscopy examinations, and immunohistochemical staining for tyrosine hydroxylase [TH], and microglia cells' markers: [CD68 and IBA1]. Results revealed that rotenone-treated rats had poor motor function, a significantly increased striatal level of inflammatory markers, markedly shrunken neurons, degeneration, pyknotic neuroglia, neuropil vacuolation, markedly destructed swollen mitochondria with loss of their cristae, and dilated rough endoplasmic reticulum, as well as decreased TH and increased CD68 and IBA1-positive cells. Treatment with EPO ameliorates all the neuropathological changes of rotenone in the rat brain. In conclusion, EPO enhanced the motor performance, reduced the inflammatory marker levels, restored dopamine levels, and ameliorated the neurohistopathological lesions of rats with experimental parkinsonism, suggesting its neuroprotective and anti-inflammatory effects.

The chemokine receptor CXCR4 regulates satellite cell activation, early expansion, and self-renewal, in response to skeletal muscle injury.

Acute skeletal muscle injury is followed by satellite cell activation, proliferation, and differentiation to replace damaged fibers with newly regenerated muscle fibers, processes that involve satellite cell interactions with various niche signals. Here we show that satellite cell specific deletion of the chemokine receptor CXCR4, followed by suppression of recombination escapers, leads to defects in regeneration and satellite cell pool repopulation in both the transplantation and in situ injury contexts. Mechanistically, we show that endothelial cells and FAPs express the gene for the ligand, SDF1α, and that CXCR4 is principally required for proper activation and for transit through the first cell division, and to a lesser extent the later cell divisions. In the absence of CXCR4, gene expression in quiescent satellite cells is not severely disrupted, but in activated satellite cells a subset of genes normally induced by activation fail to upregulate normally. These data demonstrate that CXCR4 signaling is essential to normal early activation, proliferation, and self-renewal of satellite cells.

Protective effect of Rosuvastatin on Azithromycin induced cardiotoxicity in a rat model.

AIMS: Azithromycin is widely used broad spectrum antibiotic recently used in treatment protocol of COVID-19 for its antiviral and immunomodulatory effects combined with Hydroxychloroquine or alone. Rat models showed that Azithromycin produces oxidative stress, inflammation, and apoptosis of myocardial tissue. Rosuvastatin, a synthetic statin, can attenuate myocardial ischemia with antioxidant and antiapoptotic effects. This study aims to evaluate the probable protective effect of Rosuvastatin against Azithromycin induced cardiotoxicity. MAIN METHOD: Twenty adult male albino rats were divided randomly into four groups, five rats each control, Azithromycin, Rosuvastatin, and Azithromycin +Rosuvastatin groups. Azithromycin 30 mg/kg/day and Rosuvastatin 2 mg/kg/day were administrated for two weeks by an intragastric tube. Twenty-four hours after the last dose, rats were anesthetized and the following measures were carried out; Electrocardiogram, Blood samples for Biochemical analysis of lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). The animals sacrificed, hearts excised, apical part processed for H&E, immunohistochemical staining, and examined by light microscope. The remaining parts of the heart were collected for assessment of Malondialdehyde (MDA) and Reduced Glutathione (GSH). KEY FINDINGS: The results revealed that Rosuvastatin significantly ameliorates ECG changes, biochemical, and Oxidative stress markers alterations of Azithromycin. Histological evaluation from Azithromycin group showed marked areas of degeneration, myofibers disorganization, inflammatory infiltrate, and hemorrhage. Immunohistochemical evaluation showed significant increase in both Caspase 3 and Tumor necrosis factor (TNF) immune stain. Rosuvastatin treated group showed restoration of the cardiac muscle fibers in H&E and Immunohistochemical results. SIGNIFICANCE: We concluded that Rosuvastatin significantly ameliorates the toxic changes of Azithromycin on the heart.

Protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity.

Cisplatin is broadly used in the treatment of malignancies. However, the high incidence of nephrotoxicity following cisplatin use deters its clinical utility. Former studies have shown that the essential oils, obtained from Citrus limonia demonstrated significant anti-inflammatory and antioxidant effects. The aim of the current work was to evaluate the protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity. Thirty-two adult male mice were divided into four groups, eight mice each. The control group received distilled water, and the second group received a single intraperitoneal injection of cisplatin (20 mg/kg), while the third and fourth groups received cisplatin plus Citrus limonia oil at 100 or 200 mg/kg for 10 days, respectively. GC-MS analysis showed that the major components in Citrus limonia oil were D-limonene, 5-methyl-pentadecane, (n)-menthol, 3,7-dimethyl-(E)-2,6-octadienal, 3,7-dimethyl-2,6-octadienal, and nonadecane. Biochemical analysis showed that cisplatin intoxication was associated with significantly increased (p < 0.05) serum levels of urea and creatine and pro-inflammatory cytokines, as well as augmented renal tissue oxidative stress. Light microscopic examination showed loss of renal architecture, atrophied glomeruli, interstitial hemorrhage, dilated cortical tubules with cast formation, and excessive collagen production. Electron microscopic examination revealed compressed and karyorrhectic endothelial nuclei with chromatin condensation in the glomeruli, accumulation of mesangial matrix, and obliteration of glomerular blood capillaries. Co-administration of Citrus limonia oil attenuated these effects in renal histopathological, morphometric, and ultrastructural examinations, frequently in a dose-dependent manner. In conclusion, Citrus limonia oil can ameliorate the toxic effect of cisplatin on mice kidneys, probably through its antioxidant and anti-inflammatory effects.

Effects of insulin and metformin on fetal kidney development of streptozotocin-induced gestational diabetic albino rats.

Gestational diabetes mellitus is one of common medical complications of pregnancy. Hyperglycemia in utero impairs renal development and produces renal anomalies. Metformin has antioxidant properties and better glycemic control. Aim: assessment insulin and metformin effects on renal development of streptozotocin-induced gestational diabetic albino rats. Sixty virgin female albino rats were used. Once pregnancy confirmed, animals were randomly assigned into control, metformin, diabetic, diabetic plus insulin, diabetic plus metformin and diabetic plus insulin and metformin treated groups. Rats were sacrificed on the 20th day of gestation; fetuses were extracted and weighted. Fetal kidneys were extracted prepared for light, morphometric and electron microscopic examination. Diabetic followed by diabetic plus metformin treated groups revealed retardation of glomerular development in the cortical and Juxtaglomerular zones with a significant increase in the early immature glomerular stages and immature to mature glomerular ratio compared to other groups. Diabetic group also showed morphometric changes, shrunken and empty glomeruli, vacuolar degeneration and hemorrhage. Diabetic plus metformin group showed minimal improvement while diabetic plus insulin and diabetic plus insulin and metformin groups showed developmental, histopathological and morphometric improvement with best results in the combination group. Gestational diabetes mellitus (GDM) possess deleterious effects on fetal kidney development. Insulin improves the glycemic state and decreases GDM effects on fetal kidneys. Metformin produces mild protection while the combination of insulin and metformin produces the best glycemic control and protect fetal kidneys.

Effects of maternal administration of aluminum chloride on the development of the skeletal system of albino rat fetuses - protective role of saffron

Aluminum is widely used in food packaging and additives. Aluminum chloride (AlCl3) was known to cause maternal toxicity and embryolethality. Previous studies have demonstrated the antioxidant effects of saffron. The purpose of the present study was to assess the effect of maternal administration of aluminum chloride during the period of embryogenesis on the development of the skeletal system of albino rat fetuses and the protective role of saffron. Twenty four virgin female albino rats were used throughout this study. One male rat was introduced into a cage with two females for mating. Once the pregnancy was confirmed, pregnant rats were divided into the following groups: Control, AlCl3 treated (200 mg/kg) and AlCl3+S treated (AlCl3 200 mg/kg and saffron 200 mg/kg in water extract). Rats received treatments daily from the 6th to 15th day of gestation intragastrically and sacrificed on the 20th day. The fetuses were obtained through Caesarian section, stained with Alizarin red and examined for skeletal development. AlCl3 treated rats showed toxic manifestations and decreased weight gain and their fetuses revealed increased embryolethality and a higher number of bones showed delayed ossification. AlCl3 +S treated animals revealed improvement in maternal weight gain, embryolethality and bone ossification. We conclud that AlCl3 induces delay in bone development, and saffron ameliorates its effects (AU)

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Histological and morphometric effects of CdCl2 and ginger on osteoporosis induced by bilateral ovariectomy in adult albino rats

Cadmium is a widespread environmental pollutant. Low-level environmental cadmium exposure induced osteoporosis especially in postmenopausal women. Ginger is a strong antioxidant that may play an important role in bone formation. The purpose of the present study was to assess the effects of cadmium chloride and ginger on osteoporosis induced by bilateral ovariectomy in adult albino rats. Seventy-two adult albino rat females were used in the present study. They were divided into non-operated groups and operated groups. Cadmium chloride was received at a dose of 3.5 mg/kg daily by subcutaneous injection for 8 weeks, and ginger was fed on a diet containing 5% ginger for 8 weeks. Rats were sacrificed; femurs were dissected out, fixed and decalcified. Serial transverse and longitudinal sections from the diaphysis and metaphysis of femurs were stained by haematoxylin and eosin (H&E) and Masson trichrome stainings and examined using light microscopy. Femurs of Cd-treated, ovariectomized non-treated, and ovariectomized +Cd-treated groups showed histological and morphometric osteoporotic changes that were marked and exaggerated in the ovariectomized +Cd-treated group. Whereas Cd+ginger, ovariectomized +Cd+ginger and ovariectomized+ginger treated groups showed less bone resorption, more bone formation, and improvement in bone structure and morphometric parameters compared to other groups. Cadmium chloride exposure is a risk factor for osteoporosis, especially in postmenopausal women. Ginger effectively ameliorated cadmium and ovariectomy-induced osteoporosis in rats, and is a promising candidate for the prevention and treatment of postmenopausal osteoporosis (AU)

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Morphometric study of sacral hiatus in adult human Egyptian sacra: Their significance in caudal epidural anesthesia.

BACKGROUND: The reliability and success of caudal epidural anesthesia depends on anatomic variations of sacral hiatus (SH) as observed by various authors. SH is an important landmark during caudal epidural block (CEB).The purpose of the present study was to clarify the morphometric characteristics of the SH in human Egyptian dry sacra and pelvic radiographs and identification of nearest ony landmarks to permit correct and uncomplicated caudal epidural accesses. METHODS: The present study was done on 46 human adult Egyptian dry sacra. The maximum height, midventral curved length, and maximum breadth of each sacrum were measured and sacral and curvature indices were calculated. According to sacral indices, sacra were divided into 2 groups (22 male and 24 female sacra). SH was evaluated in each sacrum according to its shape, level of its apex, and base according to sacral and coccygeal vertebrae, length, anteroposterior (AP) diameter at its apex, and transverse width at its base. Linear distances were measured between the apex of SH and second sacral foramina, right and left superolateral sacral crests. The distance between the 2 superolateral sacral crests also was measured. RESULTS: The most common types of SH were the inverted U and inverted V (in male) and inverted V and dumbbell shaped (in female). Absent SH was observed in male group only. The most common location of SH apex was at the level of S4 in all groups of dry sacra and S3 in all groups of lumbosacral spine radiographs, whereas S5 was the common level of its base. The mean SH length, transverse width of its base, and AP diameter of its apex were 2.1±0.80, 1.7±0.26, and 0.48±0.19 cm. Female sacra showed narrower SH apex than male. The distance between the S2 foramen and the apex of the SH was 4.1±1.14, 3.67±1.21, and 4.48±1.01 cm in total, female and male sacra, respectively. CONCLUSION: Sacrum and SH showed morphometric variations in adult Egyptians. The equilateral triangle is an important guide to detect SH easily and increases the success rate of CEB. Insertion of a needle into the SH for caudal block is suggested to be done at its base to avoid the anatomic variations of its apex.