Can coenzyme Q10 alleviate the toxic effect of fenofibrate on skeletal muscle?

Fenofibrate (FEN) is an antilipidemic drug that increases the activity of the lipoprotein lipase enzyme, thus enhancing lipolysis; however, it may cause myopathy and rhabdomyolysis in humans. Coenzyme Q10 (CoQ10) is an endogenously synthesized compound that is found in most living cells and plays an important role in cellular metabolism. It acts as the electron carrier in the mitochondrial respiratory chain. This study aimed to elucidate FEN-induced skeletal muscle changes in rats and to evaluate CoQ10 efficacy in preventing or alleviating these changes. Forty adult male rats were divided equally into four groups: the negative control group that received saline, the positive control group that received CoQ10, the FEN-treated group that received FEN, and the FEN + CoQ10 group that received both FEN followed by CoQ10 daily for 4 weeks. Animals were sacrificed and blood samples were collected to assess creatine kinase (CK). Soleus muscle samples were taken and processed for light and electron microscopic studies. This study showed that FEN increased CK levels and induced inflammatory cellular infiltration and disorganization of muscular architecture with lost striations. FEN increased the percentage of degenerated collagen fibers and immune expression of caspase-3. Ultrastructurally, FEN caused degeneration of myofibrils with distorted cell organelles. Treatment with CoQ10 could markedly ameliorate these FEN-induced structural changes and mostly regain the normal architecture of muscle fibers due to its antifibrotic and antiapoptotic effects. In conclusion, treatment with CoQ10 improved muscular structure by suppressing oxidative stress, attenuating inflammation, and inhibiting apoptosis.

Thymoquinone protects the testes of hypothyroid rats by suppressing pro-inflammatory cytokines and oxidative stress and promoting SIRT1 testicular expression.

Background: Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities. Objectives: This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect. Materials and methods: Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue. Results: TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated (p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated (p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased (p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased (p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased (p ˂ 0.001) in the testes of TQ-treated hypothyroid rats. Conclusion: Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.

Corrigendum: Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress.

[This corrects the article DOI: 10.3389/fpsyt.2020.569711.].

Brain-derived Neurotropic factor (BDNF) mediates the protective effect of Cucurbita pepo L. on salivary glands of rats exposed to chronic stress evident by structural, biochemical and molecular study.

BACKGROUND: Acute and chronic stresses affect the salivary glands, representing the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. OBJECTIVE: To assess the structural and biochemical effects induced by exposure to chronic unpredictable mild stress (CUMS) on salivary glands of albino rats, and to evaluate the role of pumpkin extract (Pump) in ameliorating this effect. METHODOLOGY: Four groups (n=10 each) of male albino rats were included in this study: the control, CUMS, Fluoxetine-treated and Pump-treated. The corticosterone, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the oxidant/antioxidant profile were all assessed in the serum. The level of BDNF mRNA was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. RESULTS: The depressive-like status was confirmed behaviorally and biochemically. Exposure to CUMS significantly up-regulated (p<0.001) the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal elements of the salivary glands evident by increased apoptosis. Both Fluoxetine and Pumpkin significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological and biochemical alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT, and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6. CONCLUSION: Pumpkin ameliorates the depressive-like status induced in rats following exposure to chronic stress through exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects. The pumpkin, subsequently, improved stress-induced structural changes in the salivary glands that might be due to up-regulation of BDNF expression in the glands.

Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence.

BACKGROUND: Musk (Moschus moschiferus) has been described to have a significant impact on the central nervous system, as well as anticonvulsion and antidepressant effects. This study was designed to evaluate the efficacy of musk in alleviating alterations induced in olfactory bulb of depressed mice exposed to chronic stress and identify the mechanism behind it. METHODS: Fifty male albino mice were divided into five groups (n = 10 each): control, musk, chronic unpredictable mild stress (CUMS), fluoxetine-treated, and musk-treated groups were included in this study. Behavioral changes and serum levels of corticosterone and proinflammatory cytokines included tumor necrosis factor α, interleukin 6, and oxidant/antioxidant profile were assessed at the end of the experiment. Main olfactory bulb (MOB) has been processed for histopathological examination. Gene expression of caspase-3, glial fibrillary acidic protein, and Ki67 were assessed in the MOB using quantitative real-time polymerase chain reaction. RESULTS: The study showed that musk inhalation significantly reduced (p < 0.001) corticosterone level, immobility time, inflammatory cytokines, and oxidative stress markers in CUMS-exposed mice compared to the untreated CUMS group. Musk lessened CUMS-associated neuronal alterations in the MOB and significantly reduced apoptosis and enhanced neural cell proliferation (p < 0.001) comparable to fluoxetine. Musk significantly enhanced the level of antioxidants in the serum and significantly reduced inflammatory cytokines. The anti-inflammatory and antioxidant activity of musk and its constituents seemed to be behind its neuroprotective effect observed in this study. CONCLUSION: Musk effectively ameliorated the chronic stress-induced behavioral, biochemical, and neuronal structural changes in MOB mostly through its antioxidant and anti-inflammatory effect.

Brain-derived Neurotropic factor (BDNF) mediates the protective effect of Cucurbita pepo L. on salivary glands of rats exposed to chronic stress evident by structural, biochemical and molecular study

Abstract Acute and chronic stresses affect the salivary glands, representing the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. Objective To assess the structural and biochemical effects induced by exposure to chronic unpredictable mild stress (CUMS) on salivary glands of albino rats, and to evaluate the role of pumpkin extract (Pump) in ameliorating this effect. Methodology Four groups (n=10 each) of male albino rats were included in this study: the control, CUMS, Fluoxetine-treated and Pump-treated. The corticosterone, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the oxidant/antioxidant profile were all assessed in the serum. The level of BDNF mRNA was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. Results The depressive-like status was confirmed behaviorally and biochemically. Exposure to CUMS significantly up-regulated (p<0.001) the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal elements of the salivary glands evident by increased apoptosis. Both Fluoxetine and Pumpkin significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological and biochemical alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT, and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6. Conclusion Pumpkin ameliorates the depressive-like status induced in rats following exposure to chronic stress through exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects. The pumpkin, subsequently, improved stress-induced structural changes in the salivary glands that might be due to up-regulation of BDNF expression in the glands.

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress.

BACKGROUND: Ocimum basilicum (O. basilicum) was described to have antidepressant and anxiolytic activities. Although the relationship between the main olfactory bulb (MOB) and depression was recently reported, the chronic stress-induced dysfunction of the MOB is not clearly described. OBJECTIVES: This study aimed to assess the efficacy of inhalation of O. basilicum essential oils in improving chronic unpredictable mild stress (CUMS)-induced changes in MOB of mice and understand the mechanism underlying such effect. MATERIALS AND METHODS: Adult male mice (n=40) were assigned into four groups included the control, CUMS-exposed, CUMS + fluoxetine (FLU), CUMS + O. basilicum. Behavioral changes, serum corticosterone level, and gene expression of GFAP, Ki 67, and caspase-3 were assessed using real-time PCR (RT-PCR). Histopathological and immunochemical examination of the MOB was performed. RESULTS: FLU and O. basilicum significantly down-regulated (p = 0.002, p<0.001) caspase-3 gene expression indicating reduced apoptosis and up-regulated (p = 0.002, p < 0.001) Ki67 gene expression indicating enhanced neurogenesis in MOB, respectively. FLU and O. basilicum-treated mice markedly improved MOB mitral cell layer distortion and shrinkage induced by CUMS. CONCLUSION: O. basilicum relieved both biochemically and histopathological chronic stress-induced changes in the main olfactory bulb possibly through up-regulation of gene expression of GFAP and Ki67 and down-regulation of caspase-3 in the MOB.

The protective role of musk on salivary glands of mice exposed to chronic unpredictable mild stress.

This study assessed the impact of chronic unpredictable mild stress (CUMS) on the structure of mouse salivary glands and the role of musk in alleviating this impact. Forty male albino mice were distributed equally into four groups; control (untreated), CUMS (exposed to CUMS for 4 weeks), CUMS+fluoxetine (FLU) (exposed to CUMS then treated with FLU, CUMS+musk (exposed to CUMS then treated with musk). Behavioral changes and serum corticosterone levels were assessed at the end of the experiment. The submandibular and parotid glands were dissected out and processed for histopathological and immunohistochemical examination using antibodies against alpha smooth muscle actin (ASMA) and brain-derived neurotropic factor (BDNF). Exposure to CUMS significantly (P < 0.001) increased the serum corticosterone level and induced depression. CUMS also induced vacuolation in acinar cells along with a significant (P < 0.001) reduction of ASMA immunoexpression, indicating an effect on myoepithelial cells, and a significant (P < 0.001) increase of BDNF expression in the gland ductal system. Both FLU and musk alleviated the CUMS-induced behavioral, biochemical and histopathological changes in the salivary glands. In conclusion, musk ameliorates stress-induced structural changes in mouse salivary glands. This effect might be mediated through up-regulation of BDNF secretion by the glands.

Effects of maternal age on the expression of mesenchymal stem cell markers in the components of human umbilical cord.

INTRODUCTION: Although the human umbilical cord (UC) has been previously considered a medical waste, its use as a main source of fetal stem cells for regenerative medicine applications has increased over the past few years. The aim of the study was to assess the impact of the maternal age on the expression of mesenchymal stem cells (MSC) markers CD105 and CD29 in the different areas of human UC. MATERIAL AND METHODS: In this comparative cross sectional study, one hundred term UCs from five maternal age groups (20-45 years) were collected after delivery from healthy mothers and were processed to assess both immuno- and gene expression of CD105 and CD29 surface antigen markers using immunohistochemical and RT-PCR techniques. RESULTS: The immunoexpression of CD105 and CD29 in the amniotic membrane (AM) and Wharton's jelly (WJ), the umbilical artery (UA) and the umbilical vein (UV) showed significant negative correlation with the maternal age (p < 0.001). Reduced amount of cells as well as the studied MSC markers and their gene expression levels were documented in older age mothers. CD105-positive MSCs were more abundant in the UA, whereas CD29-positive MSCs were more abundant in the AM and WJ. CONCLUSION: The decreased expression of CD105 and CD29 MSCs markers with age suggests that selective isolation of MSCs from Wharton's jelly, umbilical artery or umbilical vein of younger mothers should be recommended.

Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs.

INTRODUCTION: Few oral antidiabetic drugs have been evaluated for their reproductive complication. This study aimed to evaluate the effect of metformin, pioglitazone and sitagliptin on the structure of male reproductive system through an immunohistopathological study. MATERIAL AND METHODS: Sprague-Dawley male rats were injected with streptozotocin. The diabetic rats were divided into four groups (n = 8/each group); diabetic control, metformin-, pioglitazone- and sitagliptin-treated groups in addition to a normal control group (n = 8). At the end of the experiment, blood samples were collected for biochemical assessment. Testis, epididymis and seminal vesicle were dissected and processed for histopathological examination using routine and immune-staining. RESULTS: All drugs significantly (p < 0.05) decreased fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides and malondialdehyde compared to the diabetic control group. Metformin has induced the least pathologic changes on the structure of the testis, epididymis and seminal vesicle among the studied drugs. Metformin succeeded to restore weights of testis, epididymis and seminal vesicle as well as testosterone hormone level back to values of the NC group while the pioglitazone and sitagliptin failed to do that. A significant reduction (p < 0.05) in testicular ERa and ERb immunoexpression of pioglitazone-treated group as well as suppression of ERb and AR immunoreactivity in in epididymus and seminal vesicles of pioglitazone- and sitagliptin-treated rats were observed compared to the control animals. CONCLUSIONS: Histological structure as well ER and AR expression in the system organs were negatively and significantly affected with all studied drugs. Metformin has the least effect on the structure of the studied male reproductive organs. Thus, pioglitazone and sitagliptin treatment should be avoided in young male diabetic patients.

Is the chronic use of Ferula harmonis to enhance mice erectile function effective and safe? A histopathological study.

Many studies are aimed towards a solution for erectile dysfunction which is a worldwide health problem. Medicinal and natural herbal medications have been prescribed but their long-term effects are not well known. This study aimed to investigate the impact of the chronic administration of F. hermonis root extract on the structure of the male mice reproductive organs and their fertility and to study the possible protective role of vitamin C. Sixty male albino mice were divided into 3 groups: the control, the experimental group that received F. hermonis root extract orally (6 mg/kg) for six weeks, and the treated group that received F. hermonis plus vitamin C for six weeks. Serum testosterone level and mice fertility were assessed. At the end of the experiment mice were sacrificed; testis, epididymis, and seminal vesicle were dissected and processed for routine histopathological and immunohistochemical examination. The chronic administration of F. hermonis extract significantly decreased the level of testosterone and partially impaired fertility. Histopathological degenerative changes and a significant reduction in estrogen receptor (ER)ß expression were observed in testes, epididymis, and seminal vesicle. Vitamin C administration did not completely protect the testis from these harmful effects. Although F. hermonis roots are recommended to improve erectile and fertility problems, it should be used for short periods and with extreme caution. Further clinical studies to assess safety and efficacy are needed.

Can garlic oil ameliorate diabetes-induced oxidative stress in a rat liver model? A correlated histological and biochemical study.

This study aimed to characterise the structural changes in liver of an alloxan-induced diabetic rat and to explain such changes in terms of the biochemical changes in free radicals and antioxidants. In addition, it aimed to determine the potential ability of garlic oil to alter these changes. The study groups were: control (n=12), alloxan-induced diabetic rats (n=10) and alloxan-induced diabetic rats treated with garlic oil (10 mg/kg body weight (n=10)). Markers of oxidative stress were assessed. Small pieces of the liver were processed for transmission electron microscopic study. Garlic oil caused a significant decrease in levels of LPO in plasma (0.26 vs 0.53), erythrocyte lysate (14.4 vs 24.8) and liver tissue homogenate (1.04 vs 2.08), whereas those of thiols were significantly elevated (1.2 vs 0.46), (24 vs 15) in plasma and erythrocyte lysate respectively. SOD activity and G-S-T activity were significantly elevated in erythrocyte lysate (5.7 vs 3.3) (377 vs 179) and liver homogenate (1.4 vs 0.5) (752 vs 623) respectively after garlic oil administration. Ultrastructural study of the liver confirmed the ability of garlic to retard lipid peroxidation of cellular membranes induced by oxidative stress associated with diabetes. Therefore, garlic could normalise oxidative stress in alloxan-induced diabetic rats.

Impact of medical curriculum on conceptualization of professionalism by residents at a University Hospital, Jeddah, Saudi Arabia.

BACKGROUND: The quality of healthcare outcomes and patient satisfaction are affected by communication skills and professionalism of the physician. Medical curricula have substantial influence on physicians' perception of professionalism. OBJECTIVES: The aim of this study was to determine the impact of medical curriculum on the values of the residents at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, and their opinions on professionalism and to identify the sources that they describe as most influential in shaping their views. METHODS: This cross sectional study was conducted in 2010/2011. A modified version of the questionnaire designed by Blue and colleagues was distributed among the target group (n=201). Psychometric analysis of the survey tool showed that it was precise and had construct validity. RESULTS: The return rate was 76.6%. The overall means of the attitudes of both male and female residents toward the attributes of professionalism were low. Attitude toward professionalism showed an insignificant difference between male and female residents. Self-reflection ranked first among all studied attributes. Most male (80%) and female (76.7%) residents believed that working with consultants, specialists, and senior residents in the hospital was the main source of their opinions on professionalism. They considered basic science studies and the other extracurricular courses they attended to be the least helpful in developing their opinions. CONCLUSION AND RECOMMENDATIONS: Residents at King Abdulaziz University Hospital feel underserved in the area of developing their values toward professionalism during the preclinical years, relying to some extent on their experiences during their clinical years and mainly on their interactions with consultants, colleagues, and hospital staff to develop their sense of professionalism. Given the recent changes in the curriculum adopted by the university, it is recommended to assess the attitudes of the students under the new curriculum toward professionalism and to compare them with those of students under the traditional curriculum.

Interdisciplinary integration of the CVS module and its effect on faculty and student satisfaction as well as student performance.

BACKGROUND: Beyond the adoption of the principles of horizontal and vertical integration, significant planning and implementation of curriculum reform is needed. This study aimed to assess the effect of the interdisciplinary integrated Cardiovascular System (CVS) module on both student satisfaction and performance and comparing them to those of the temporally coordinated CVS module that was implemented in the previous year at the faculty of Medicine of the King Abdulaziz University, Saudi Arabia. METHODS: This interventional study used mixed method research design to assess student and faculty satisfaction with the level of integration within the CVS module. A team from the medical education department was assembled in 2010/2011 to design a plan to improve the CVS module integration level. After delivering the developed module, both student and faculty satisfaction as well as students performance were assessed and compared to those of the previous year to provide an idea about module effectiveness. RESULTS: Many challenges faced the medical education team during design and implementation of the developed CVS module e.g. resistance of faculty members to change, increasing the percentage of students directed learning hours from the total contact hour allotted to the module and shifting to integrated item writing in students assessment, spite of that the module achieved a significant increase in both teaching faculty and student satisfaction as well as in the module scores. CONCLUSION: The fully integrated CVS has yielded encouraging results that individual teachers or other medical schools who attempt to reformulate their curriculum may find valuable.

Vascular and cellular events in post-mastectomy seroma: an immunohistochemical study.

This study aimed to describe the vascular and cellular histopathological changes that occurred in post-mastectomy seroma in an animal model. Unilateral mastectomies were conducted on 45 female albino rabbits. On day seven, the skin flap and the underlying tissues of the mastectomy regions were dissected and processed for histopathological examination using immunohistochemical staining of the T- and B-lymphocytes and macrophages (CD3, CD20, and CD68 respectively), and the vascular endothelia. The post-mastectomy regions in the seroma group showed a large number of inflammatory cells and newly formed blood vessels that lost the integrity of their endothelial cell linings, as revealed by the von Willebrand factor staining, as well the basement membrane, as revealed by the histochemical stain. The post-mastectomy seroma beds showed many CD3 and CD20+ve lymphocytes and CD68+ve macrophages. These macrophages were producing angiogenic factors, resulting in the persistent and continuous formation of new blood vessels. These new blood vessels were defective and represented an underlying cause of seroma formation.

Morphological and morphometric study of cultured fibroblast from treated and untreated abnormal scar.

OBJECTIVE: To investigate the morphology of cultured fibroblasts derived from abnormal scars and compare it to those of human normal skin. METHODS: This study was carried out in the Surgical Clinic, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between December 2008 and March 2010. Fifty-two samples of hypertrophic and keloid scar were collected. An in vitro study was conducted in which fibroblasts from normal foreskin; abnormal scars were cultured, studied morphologically and morphometrically. RESULTS: There was a highly significant increase in the length and breadth of fibroblasts from the hypertrophic and keloid scars, and highly significant decrease in the bipolarity index compared to control. There was a significant increase in the mean cell area, mean nuclear area and nuclear/cytoplasmic ratio of fibroblast of hypertrophic and keloid scars compared to control. There was a significant decrease in the mean cell area and mean nuclear area of the fibroblast of the treated keloid scar (with all used modalities) compared to untreated ones. Morphologically, abnormal scar fibroblasts has abundant spreading cytoplasm with numerous processes and large nuclei. The cytoplasm, of some cells, contained clumped granules in the peri-nuclear region, numerous vacuoles, and dense vesicles. CONCLUSION: Morphological and morphometric study showed that hyperactive cultured fibroblasts was a characteristic feature of abnormal scars and the studied modalities of treatment reduced, but not completely nullify this activity.