The Possible Effects of Vitamin D3 on AlCl3-Induced Histological and Morphometric Alterations of Adult Male Albino Rat Hippocampus.

Context: Alzheimer's disease (AD) is a challenging neurodegenerative disease, and Vitamin D was proved to have neuroprotective effects. Aim: This study was conducted to evaluate the potential neuroprotective effects of Vitamin D3 supplementation on AlCl3-induced AD rat model in different hippocampal subregions (CA1, CA2, and CA3). It also aimed to compare the protective effects of protective versus therapeutic effects of Vitamin D3 regiments on the number of degenerated neurons and the neuronal layer thickness. Materials and Methods: Twenty-four adult male Albino Wister rats were sorted into GI: control; GII: AlCl3-AD model (100 mg/kg) orally for 42 days; GIII: Rats were co-treated with AlCl3 (as GII) and Vitamin D3 (400 IU/kg/day) orally for 42 days; GIV: Rats were treated with AlCl3 for 42 days then with Vitamin D3 for further 2 weeks. Sagittal sections (5 µ) from paraffin-processed brains previously fixed in 10% neutral-buffered formalin were stained with hematoxylin and eosin to evaluate the thickness and number of degenerated neurons in the hippocampal CA1, CA2, and CA3 subregions. Statistical Analysis: The results of this study were expressed as mean ± standard deviation and analyzed by using IBM SPSS Statistics for Windows, version 23 (IBM SPSS, IBM Corp., Armonk, N.Y., USA). P < 0.05 was considered statistically significant. Results: Vitamin D3 supplementations modulated the degenerative changes observed in the hippocampus of AD rat model. In all hippocampal subregions, the thickness was higher in rats treated with Vitamin D3 after the AD induction than rats treated with Vitamin D3 during AD induction. However, this increase was only significant in CA2. Comparison of the number of degenerated neurons between both groups treated with Vitamin D3 revealed that in CA1, the number of degenerated neurons did not statistically differ between the two groups. However, it was insignificantly lower in CA2 in rats treated with Vitamin D3 after the AD induction, and in CA3, it was insignificantly lower in rats treated with Vitamin D3 during the AD induction. Conclusions: Vitamin D3 was found to be effective in ameliorating histological and morphometric alterations in AlCl3-induced AD in rat model and could be proposed as both preventive and therapeutic supplements in high-risk AD patients.

Elevated Salivary Inflammatory Biomarkers are Associated with SARS-CoV-2 Infection Severity.

High levels of inflammatory cytokines in serum have been reported in patients with severe SARS-CoV-2 infection. There is growing interest in recognizing the role of inflammatory biomarkers in saliva in diagnosing systemic diseases. This study assumed that estimating biomarkers in saliva samples from patients infected with SARS-CoV-2 would distinguish between mild and severe cases. Saliva was collected from 142 controls and 158 SARS-CoV-2 patients (mild 72 and severe 86) to measure interleukin-6 (IL-6), C-reactive protein (CRP), and C-X-C motif chemokine ligand-10 (CXCL-10). IL-6 and CXCL-10 were significantly increased in patients with mild and severe SARS-CoV-2 infections. CRP was significantly increased only in severe SARS-CoV-2 cases. All biomarkers were significantly higher in severe cases than in mild cases (p < 0.001). Among patients with SARS-CoV-2 infection, men showed significantly higher CRP and CXCL-10 levels than females (p < 0.01 and 0.05, respectively). In addition, elderly patients (40-80 years) had significantly higher IL-6, CRP, and CXCL-10 (p < 0.001). Patients with diabetes and hypertension showed elevated IL-6, CRP, and CXCL-10 (p < 0.001). There was a significant positive correlation between IL-6, CRP, CXCL-10, and between age, IL-6, CRP, and CXCL-10. Saliva may have a future value in measuring the inflammatory biomarkers associated with the severity of SARS-CoV2 infection and therapeutic monitoring.

Biochemical and Histological Study of the Impact of Combined Lepidium sativum and Citric Acid on Liver and Kidney Functions in Rats.

The study aimed to determine the interaction of using LS and CA in combination on liver, kidney, and heart functions in rats and to evaluate the role of antioxidant effects of LS against CA-induced hepato-renal toxicity. This study was conducted on 36 male rats divided into four groups (n = 9). The groups were; the control, LS-treated (10 g/100 g of food), CA-treated (5 g/100 g of food), and combined LS plus CA-treated groups for 6 weeks. Kidney, liver and heart functions as well as oxidant/antioxidant profile were biochemically assessed in the serum using ELISA. The impact of LS and CA on kidney and liver was histopathologically assessed. Rats fed on diet supplemented with LS for 6 weeks showed no significant change in serum levels of the biochemical markers of liver, kidney and heart functions, while supplementation with CA significant increased (p < 0.001) the serum levels of these markers compared to the control group. Combined administration of LS and CA significantly reduced the serum levels of these parameters compared to CA-treated group. Oxidative markers significantly increased while the antioxidants one decreased in CA-treated group compared to the control. Combined LS and CA significantly improve the oxidant/antioxidant profile as well as histopathological impact compared to CA-treated group.

Novel Pomegranate-Nanoparticles Ameliorate Cisplatin-Induced Nephrotoxicity and Improves Cisplatin Anti-Cancer Efficacy in Ehrlich Carcinoma Mice Model.

Cisplatin (CISP) is one of the most widely used anti-cancer chemotherapeutic agents with remarkable efficacy against various types of cancers. However, it has been associated with nephrotoxicity amongst other undesirable side effects. Pomegranate (PE) is a potent antioxidant and anti-inflammatory agent effective against cancer, with a superior benefit of not being associated with the common toxicities related to the use of conventional chemotherapeutic agents. However, the application of PE is limited by its reduced solubility and decreased bioavailability. We investigated the potential of a novel nanoparticle (NP) enclosing PE to enhance its solubility and improve its bioavailability, and efficacy to prevent CISP-associated nephrotoxicity in a mice model of Ehrlich solid carcinoma (ESC). All mice were grouped into four cohorts: (I) control, (II) tumor, (III) CISP, and (IV) CISP + PE-NPs. The data obtained demonstrated that PE-NPs was beneficial in potently ameliorating CISP-induced nephrotoxicity in ESC mice. PE-NPs significantly attenuated CISP-induced oxidative stress and lipid peroxidation in the kidney via improving activities of antioxidants (SOD, GSH, and CAT). Additionally, PE-NPs considerably decreased CISP-induced inflammation in the kidney by decreasing the levels of NF-kB, IL-1ß, and TNF-α. Notably, PE-NPs did not assuage the antitumor efficacy of CISP as revealed by histological assessment and tumor weight data. In summary, PE-NPs may be a potent alternative anticancer therapy devoid of nephrotoxicity.

Nanoparticles of Costus speciosus Ameliorate Diabetes-Induced Structural Changes in Rat Prostate through Mediating the Pro-Inflammatory Cytokines IL 6, IL1ß and TNF-α.

Diabetes mellitus is a common global health problem. Among the complications that are frequently associated with DM are the alternation of sexual function and fertility, especially in young men. This study aimed to assess the efficacy of nanoparticles of Costus speciosus (C. speciosus) in preserving the prostatic structure of diabetic rats and to explore the mechanism behind this effect. A model of DM was induced in male albino rats by a single intraperitoneally injection of streptozotocin (STZ, 60 mg/kg body weight). Five groups (n = 10 each) of rats were included in this study: the control, C. speciosus gold nanoparticles-treated (150 mg/kg body weight through gastric intubation for 30 days), untreated diabetic, metformin-treated diabetic (500 mg/kg/day gastric intubation for 30 days) and the C. speciosus-treated diabetic group. The blood glucose, insulin and testosterone levels as well as oxidants/antioxidants status were assessed in the serum. Gene expression of proinflammatory cytokines TNF-α, IL1ß and IL-6 were assessed in the prostate homogenate. At the end of the experiment, the rats were sacrificed and the prostate was dissected out and prepared for histopathological and immunohistochemistry study using Ki67 and Bcl-2. C. Speciosus nanoparticles significantly decreased (p = 0.03) the blood glucose level while significantly increasing insulin (p = 0.01) and testosterone (p = 0.04) levels compared to the untreated diabetic rats. Oxidants/antioxidants status was markedly improved after administration of C. speciosus. Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1ß and TNF-α was down-regulated in metformin- and C. speciosus-treated rats. The histological structure of the ventral prostate was preserved in metformin- and C. speciosus-treated diabetic rats with a significantly thicker epithelial cell layer and significant increase immunoexpression in Bcl-2 and Ki67. In conclusion, the protective effect induced by C. speciosus nanoparticles on the prostate of diabetic rats might be directly mediated through the down-regulation of inflammatory cytokines and the up-regulation of antioxidant activity and indirectly mediated through the anti-hyperglycemic effect through enhancing insulin secretion.

Thymoquinone Preserves Pancreatic Islets Structure Through Upregulation of Pancreatic ß-Catenin in Hypothyroid Rats.

BACKGROUND: Altered status of thyroid hormones, which have a key role in regulating metabolism, was reported to affect glucose homeostasis and insulin secretion. OBJECTIVE: This study was designed to assess the impact of propylthiouracil (PTU)-induced hypothyroidism on the pancreatic islet cells and the efficacy of thymoquinone (TQ) in alleviating this impact and explore the mechanism behind it alleviating oxidative stress and affecting ß-catenin expression. MATERIALS AND METHODS: PTU (6 mg/kg/body weight) was used to induce hypothyroidism in Wistar rats. Four groups of rats (n=6 each) were utilized in this study. Untreated hypothyroid and TQ-treated hypothyroid groups (50 mg/kg/body weight for 4 weeks) were included. Thyroid functions, antioxidant profile and pancreatic ß-catenin and IL-10 mRNA were measured. Histopathological and immunohistochemical assessment of the pancreas was performed. RESULTS: PTU administration induced a hypothyroid status that was associated with a marked disturbed oxidant/antioxidant status and a significant hyperglycemia (p<0:001), hypoinsulinemia (p=0.01) and decreased HOMA-ß-cell (p<0.001). Islet cells of hypothyroid pancreas showed many degenerative changes with increased apoptosis, reduced insulin ß-catenin immunoexpression. Administration of TQ alleviated these effects on the thyroid function, antioxidants, structure of pancreatic islet cells. Up-regulation of ß-catenin, IL-10 and CAT gene expression in pancreatic islets after treatment with TQ supported its antioxidant and preserving ß-cell function and viability mechanistic action. CONCLUSION: TQ alleviated PTU-induced hypothyroidism changes in insulin homeostasis and pancreatic ß cells mostly through its antioxidant effect as well as up-regulation of pancreatic ß-catenin expression.

Vitamin E and 5-amino salicylic acid ameliorates acrylamide-induced peripheral neuropathy by inhibiting caspase-3 and inducible nitric oxide synthase immunoexpression.

Acrylamide is a fundamental cause of accidental toxicity in humans. This study aimed to investigate the neuroprotective effect of vitamin E (Vit. E), 5-amino salicylic acid (5-ASA), and their combination against acrylamide-induced sciatic nerve toxicity. For this purpose, 25 male Wister rats were divided into 5 groups: control, acrylamide, acrylamide + Vit. E, acrylamide + 5-ASA, and acrylamide + Vit. E + 5-ASA. Food intake and body weight were assessed after 7 days. Furthermore, the gait score was also evaluated for each rat. The sciatic nerve was dissected, fixed, and processed for routine light and electron microscopic examination. Haematoxylin and eosin, osmium tetroxide for myelin sheath, and toluidine blue for semithin section were used. In addition, immunohistochemistry for caspase-3 and inducible nitric oxide synthase (iNOS) were performed. The results showed reduced food intake and body weight in acrylamide rats. Abnormal gait score was also recorded in acrylamide rats with significant improvement in Vit. E, and Vit. E + 5-ASA groups. Histologically, Vit. E and 5-ASA provided potential protection against decreased sciatic nerve axon density, disrupted myelination, and the alteration in the immunohistochemistry induced by acrylamide. Vit. E and its combination with 5-ASA provided more evident protection compared to 5-ASA alone. 5-ASA significantly decreased apoptotic cell death (caspase-3 immunoexpression) while Vit. E failed. Both Vit. E and 5-ASA significantly decreased iNOS immunoexpression in the sciatic nerve, where 5-ASA was superior to Vit. E. These findings concluded that both Vit. E and 5-ASA protect against acrylamide-induced peripheral neuropathy through downregulation of both caspase-3 and iNOS immunoexpression.

Zingiber officinale preserves testicular structure and the expression of androgen receptors and proliferating cell nuclear antigen in diabetic rats.

The aim of this study was to assess the efficacy of Zingiber officinale, commonly referred to as ginger, in preserving the structural integrity of testis in streptozotocin (STZ)-induced diabetic rats compared to the efficacy of metformin, the traditional effective antidiabetic drug. STZ was utilised for the induction of diabetes mellitus in male Sprague Dawley rats. The study included five groups (n = 6 each), namely the normal control, ginger-treated normal, nontreated diabetic, metformin-treated diabetic and ginger-treated diabetic groups. Biochemical assessment of fasting blood glucose level (BGL) and total antioxidant capacity (TAC) was performed. Histopathological assessment of the testes was performed using routine and immunohistochemical techniques. Fasting BGL significantly (p = .01) reduced, whereas TAC significantly increased (p < .001) in metformin- and ginger-treated diabetic rats compared to those in untreated diabetic rats. Metformin and ginger reduced the degenerative changes observed in the testes of diabetic rats, significantly reduced (p < .001) caspase-3 immunoexpression, and significantly increased (p < .001) the immune-expression of androgen receptors and proliferating cell nuclear antigen. Ginger has antidiabetic effects and preserves testicular structural integrity and, thus, is recommended as an adjuvant therapy for male diabetic patients in the reproductive period.

Both Matricaria chamomilla and Metformin Extract Improved the Function and Histological Structure of Thyroid Gland in Polycystic Ovary Syndrome Rats through Antioxidant Mechanism.

There is increasing proof that polycystic ovary syndrome (PCOS) is associated with the increased frequency of thyroid disturbances. Chamomile (Matricaria chamomilla L.) herb and metformin showed therapeutic efficacy against polycystic ovary syndrome (PCOS). This study aimed to investigate the possible therapeutic effect of both chamomile flower extract and metformin against thyroid damage associated with PCOS in rats. The PCOS model was developed in rats by injecting estradiol valerate, and it was confirmed to be associated with thyroid hypofunction biochemically and pathologically. Treatment of PCOS rats with both chamomile extract and metformin resulted in an improvement in serum level of thyroid hormones (TSH, p < 0.01; T3 and T4, p < 0.05) and the disappearance of most thyroid gland pathological changes demonstrated by light and electron microscopes. They also reduced the level of serum estrogen (p < 0.01). Both chamomile extract and metformin decreased MDA (p < 0.05) and increased GPx and CAT (p < 0.01). Only chamomile extract increased GSH (p < 0.01). Both treatments reduced the apoptotic death of thyroid cells as noted by the reduction of caspase-3 immunoexpression (p < 0.01). In conclusion, both Matricariachamomilla extract and metformin ameliorated hypothyroidism associated with PCOS through an antioxidant and antiapoptotic mechanism.

Improved histoarchitectural changes with angiotensin receptor blockers in early testicular and cauda toxicity in rats / Mejora de los cambios en la histoarquitectura con bloqueadores de receptores de angiotensina en la toxicidad precoz testicular y de cauda en ratas

SUMMARY: Reproductive dysfunction is a complication for many diseases and toxins. Its early diagnosis and treatment are immensely important. Here the morphological histoarchitecture changes in early testicular and cauda toxicity before and after treatment with angiotensin receptor blockers were evaluated. Low-grade testicular damage was induced using thioacetamide (TAA, 50 mg/kg/day) intraperitoneally for two weeks in rats. The rats were randomly divided into four groups (n = 8) treated daily orally for three weeks as follows: Normal control (distilled water), TAA (positive control), TAA+candesartan (0.2 mg/kg) and TAA+losartan (7.5 mg/kg). Serum testosterone and testicular malondialdehyde and glutathione were measured. The changes in histoarchitecture of testis and cauda epididymis were evaluated by hematoxylin and eosin for general structure, Masson's trichrome for collagen, periodic acid Schiff for basement membrane, and caspase-3 and proliferating cell nuclear antigen (PCNA) for immunohistochemical analysis. The TAA-rats showed decreases of serum testosterone and testicular glutathione, increases in testicular malondialdehyde, degenerative changes and apoptosis in germ cells, thickening of tubular basal lamina and increases in expression of caspase 3, and decreases in expression of PCNA. The ARBs (candesartan and losartan) significantly reversed these changes with non-significant differences in-between. Treatment with ARBs (candesartan and losartan) significantly reversed TAA-induced low-grade testicular and cauda toxicity in rats. This could be potentially useful for early treatment of male patients with occupational toxicant-induced reproductive dysfunction especially if they are using ARBs for other comorbidities.

RESUMEN: La disfunción reproductiva es una complicación por muchas enfermedades y toxinas. Su diagnóstico y tratamiento tempranos son inmensamente importantes. Aquí se evaluaron los cambios morfológicos en la histoarquitectura en la toxicidad precoz testicular y cauda antes y después del tratamiento con bloqueadores de receptores de angiotensina. Se indujo daño testicular de bajo grado usando tioacetamida (TAA, 50 mg / kg / día) por vía intraperitoneal durante dos semanas en ratas. Las ratas se dividieron aleatoriamente en cuatro grupos (n = 8) tratados diariamente por vía oral durante tres semanas de la siguiente manera: control normal (agua destilada), TAA (control positivo), TAA + candesartan (0,2 mg / kg) y TAA + losartán (7,5 mg / kg). Se midieron la testosterona sérica, el malondialdehído testicular y el glutatión. Los cambios en la histoarquitectura de los testículos y la epidermis de la cauda se evaluaron mediante Hematoxilina y Eosina para determinar la estructura general, con tricrómicro de Masson para el colágeno, ácido periódico de Schiff para la membrana basal y la caspasa-3 y el antígeno nuclear de células proliferantes (PCNA) para análisis inmunohistoquímico. Las ratas TAA mostraron disminución de la testosterona sérica y glutatión testicular, aumentos en el malondialdehído testicular, cambios degenerativos y apoptosis en células germinales, engrosamiento de la lámina basal tubular y aumentos en la expresión de la caspasa 3, y disminución en la expresión de PCNA. Los ARB (candesartán y losartán) revirtieron significativamente estos cambios con diferencias no significativas en el medio. El tratamiento con BRA (candesartán y losartán) revirtió significativamente la toxicidad testicular y cauda inducida por TAA en ratas. Esto podría ser potencialmente útil para el tratamiento temprano de pacientes con disfunción reproductiva inducida por tóxicos ocupacionales, especialmente si están usando BRA para otras comorbilidades.

Ameliorative Effect of Camel's Milk and Nigella Sativa Oil against Thioacetamide-induced Hepatorenal Damage in Rats.

BACKGROUND: Camel milk (CM) and Nigella sativa (NS) have been traditionally claimed to cure wide range of diseases and used as medicine in different part of world, particularly in Saudi Arabia. Several research studies have been published that proved beneficial effects of CM and NS. OBJECTIVE: This study was undertaken to investigate the antihepatotxic potential of CM and NS oil (NSO) against thioacetamide (TAA)-induced hepato and nephrotoxicity in rats. MATERIALS AND METHODS: Thirty female Albino Wistar rats were randomly divided in to six groups having five rats in each group. A single subcutaneous injection of TAA (100 mg/kg b. w.) was administered to all the rats in Group-II to VI on 1st day to induce hepatorenal damage. Group I served as a normal control while Group II served as toxic control for comparison purpose. Experimental animals in Group III, IV, and V were supplemented with fresh CM, (250 mL/24 h/cage), NSO (2 mL/kg/day p. o.), and NSO + fresh CM, respectively. Group VI was treated with a polyherbal hepatoprotective Unani medicine Jigreen (2 mL/kg/day p. o.) for 21 days. TAA-induced hepatorenal damage and protective effects of CM and NSO were assessed by analyzing liver and kidney function tests in the serum. Histopathology of liver and kidney tissues was also carried out to corroborate the findings of biochemical investigation. RESULTS: The results indicated that the TAA intoxicated rats showed significant increase in the alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, lipid profile, urea, creatinine, uric acid, sodium, and potassium levels in serum. Treatment of rats with CM, NSO, and CM plus NSO combination and Jigreen significantly reversed the damage and brought down the serum biochemical parameters and lipid profile toward the normal levels. The histopathological studies also support the hepato and nephroprotective effects of CM and NSO. CONCLUSION: This study demonstrated the ameliorative effects of CM, NSO, and CM plus NSO combination against TAA-induced hepatorenal toxicity in rats. SUMMARY: The antihepatotxic potential of Camel's Milk (CM) and Nigella sativa oil (NSO) against thioacetamide (TAA) induced hepatorenal toxicity was evaluated in ratsThe oral administration of fresh CM (250 mL/24h/cage), NSO (2 mL/kg/day) and NSO+fresh CM and Jigreen (2 mL/kg/day) for 21 days significantly decreased the hepatorenal toxicity as evidenced from analyzed biochemical parameters in serum and histopathological studies of liver and kidney tissuesThis study demonstrated the ameliorative effects of CM and NSO against TAA induced hepatorenal toxicity. Abbreviations used: CM: Camel milk; NS: Nigella sativa; NSO: Nigella sativa Oil; TAA: Thioacetamide; S.C.: Subcutaneous; Jig: Jigreen; b.w.: Body Weight; mL: Milli liter; mg: Milli gram; g: Gram; Kg: Kilo gram; ALT: Alanine transaminase; AST: Aspartate transaminase; GGT: Gamma-Glutamyl Transpeptidase; ALP: Alkaline Phosphatase; TC: Total Cholesterol; HDL-C: High Density Lipoprotein Cholesterol; LDL-C: Low Density Lipoprotein Cholesterol; TG: Triglyceride; TB: Total bilirubin; K+: Potassium; Na+: Sodium; CCl4: Carbon Tetrachloride; °C: Degree Celsius; p.o.: Per Oral; RPM: Revolutions per minute; H&E: Hematoxylin and Eosin; SEM: Standard Error of Mean; ANOVA: The one-way analysis of variance.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

OBJECTIVE: This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). MATERIAL AND METHODS: Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. RESULTS: Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. CONCLUSION: Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

Correction to: The antidepressant effect of musk in an animal model of depression: a histopathological study.

The original publication of this paper contains mistake. Below you will find the needed corrections.

The antidepressant effect of musk in an animal model of depression: a histopathological study.

Depression is a significant public health concern all over the world, especially in modern communities. This study aims to assess the efficacy of musk in alleviating the behavioral, biochemical and histopathological changes induced by chronic unpredictable mild stress (CUMS) in an animal model of depression and to explore the underlying mechanism of this effect. Male Swiss albino mice were divided into four groups (n = 10): control, CUMS, CUMS+fluoxetine and CUMS+musk. At the end of the experiment, behavioral tests were administered and serum corticosterone and testosterone levels were assessed. Surface markers, proteins and gene expressions of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) in the hippocampus were assessed. The immunoexpression of glial fibrillary acidic protein, Ki67 and caspase-3 was also assessed. Data were analyzed using the Statistical Package for the Social Sciences and a P value of less than 0.05 was considered significant. Musk alleviated the behavioral changes caused by CUMS and reduced elevated corticosterone levels. It reduced CUMS-induced neuronal atrophy in the CA3 and dentate gyrus of the hippocampus and restored astrocytes. Musk reduced the neuro- and glial apoptosis observed in stressed mice in a manner comparable to that of fluoxetine. Musk induced these effects through up-regulating both BDNF and GR gene and protein expressions. Musk has an antidepressant-like effect in an animal model of depression, so it is advisable to assess its efficacy in people continually exposed to stressors.

Antihyperglycemic effect of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals.

BACKGROUND: Diabetes mellitus is one of the most important diseases related with endocrines. Its main manifestation includes abnormal metabolism of carbohydrates and lipids and inappropriate hyperglycemia that is caused by absolute or relative insulin deficiency. It affects humankind worldwide. OBJECTIVES: Our research was aimed to observe antihyperglycemic activity of thymoquinone and oleuropein. MATERIALS AND METHODS: In this study, rats were divided into six groups, 6 rats in each. Diabetes was inducted by streptozotocin (STZ). The level of fasting blood glucose was determined for each rats during the experiment, doses of thymoquinone and oleuropein (3 mg/kg and 5 mg/kg) for both, were injected intraperitoneal. Pancreatic tissues were investigated to compare ß-cells in diabetic and treated rats. RESULT AND CONCLUSION: It was found that thymoquinone and oleuropein significantly decrease serum Glucose levels in STZ induced diabetic rats.

Does the maternal age affect the mesenchymal stem cell markers and gene expression in the human placenta? What is the evidence?

BACKGROUND: Although the human placenta is considered medical wastes, it has become a main source of stem cells. Due to their easy isolation, ability to resist immune rejection and ability to differentiate into different types of adult cells, placental stem cells are considered superior to other stem cells. OBJECTIVES: This study aimed to assess the impact of the maternal age on the expression of mesenchymal stem cell (MSC) markers CD105 and CD29 in different areas of a term human placenta and to identify the differential expression of these markers in different placental areas. SUBJECTS AND METHODS: In this comparative cross sectional study, one hundred term placentas were collected after delivery from healthy mothers divided into five groups according to their age. Placentas were processed to assess both immune- and gene-expression of CD105 and CD29 surface antigen markers. Data of the different studied age groups was compared using the Statistical Package of Social Science (SPSS) software. RESULTS: CD105 and CD29 immunoexpression in decidua basalis, fetal membrane and placental villi showed significant negative correlations with the maternal age. CD105- and CD29-positive MSCs were significantly abundant in the decidua basalis and placental villi. Real-time polymerase chain reaction results were consistent with those of the immunohistochemical study. CONCLUSION: Labeling the placenta-driven MSCs with the specific area from which the cells were taken as well as the mother's age is advised and could be helpful in controlling the quality of the cell banks as well as the favorable outcome of the therapeutic applications.

Effects of different routes of nicotine administration on gastric morphology and hormonal secretion in rats.

NEW FINDINGS: What is the central question of this study? Does chronic administration of nicotine by different routes affect gastric hormonal secretions and morphology in rats? What is the main finding and its importance? Chronic nicotine administration increased levels of gastrin, ghrelin and histamine but decreased prostaglandin E2 . Nicotine administered orally and by inhalation had a marked negative impact on the histological structure of the gastric mucosa compared with intraperitoneal administration. The negative impact of nicotine administration on gastric structure was associated with an increased concentration of gastrin and decreased prostaglandin E2 , which might be the cause of gastric/peptic ulcers in heavy smokers. The increase in ghrelin concentration and its effect following chronic nicotine administration needs further investigation. The aim was to assess the effects of different routes of chronic nicotine administration on gastric morphology and hormonal secretion; mainly gastrin, ghrelin, histamine and prostaglandin E2 (PGE2 ). Forty adult male albino rats were randomly assigned into four groups (10 rats per group), treated for 21 days as follows: control group (given standard rat pellets and water only); oral nicotine-treated group [50 µg (ml drinking water)(-1) ]; intraperitoneal nicotine-treated group [0.5 mg (kg body weight)(-1) ]; and inhaled nicotine-treated group [0.5 mg (kg body weight)(-1) ]. Concentrations of gastrin, ghrelin, PGE2 and histamine in serum and gastric tissue homogenates were assessed using ELISA kits. Stomach fundus was processed for histopathology and immunohistochemistry using light and electron microscopy. Different routes of chronic nicotine administration resulted in a significant increase in serum and gastric homogenate gastrin and ghrelin concentrations and a significant decrease in serum and homogenate PGE2 concentrations compared with the control group. Moreover, nicotine administration via oral and inhalation routes caused gastric erosion, transformation of peptic cells into the mucous variety, a significant increase in parietal cell numbers and an increase in expression of gastrin. In conclusion, the negative impact of nicotine administration on gastric structure that is associated with an increased concentration of gastrin and decreased concentration PGE2 might be the leading cause of gastric/peptic ulcers in heavy smokers. The increased ghrelin concentration and its effect following nicotine chronic administration needs further investigation. Based on these findings, we suggest that the alteration in gastric structure following chronic administration of nicotine can be prevented by reducing gastrin secretion and/or targeting its receptors.

Amelioration of hypercholesterolemia-induced hepatic changes with red grape juice: A histopathological study.

OBJECTIVES: Hypercholesterolemia was confirmed as a risk factor for hepatic fibrosis, as well atherosclerosis and coronary heart disease. This biochemical and histoplathological study was conducted to investigate the possible protective effect of red grape against hepatic injury induced by a high-cholesterol diet (HCD). MATERIAL AND METHODS: Thirty male Wister rats were randomly divided into three groups (n=10): the control received saline, the induction group was fed HCD, and the treated group was fed a HCD and 0.4 ml of 100% red grape juice (RGJ) for 13 weeks. After the animals were sacrificed, liver tissue samples were taken to be processed for light and electron microscopy examination. RESULTS: The administration of the RGJ and HCD significantly decreased the animals' blood glucose, insulin, cholesterol, triglycerides, Low Density Lipoprotein levels and increased their High Density Lipoprotein level compared to the rats fed the HCD alone. It also decreased the periportal (macro- and microvesicular) steatosis, fibrosis, lymphocytic infiltration and blood sinusoidal congestion that were observed in HCD-fed rats alone. The RGJ reduced the number of activated myofibrobasts. This was confirmed by a reduction in the expression of alpha smooth muscle actin and desmin. The RGJ increased, although not significantly, the expression of endothelial Nitric Oxide Synthetase. CONCLUSION: The administration of RGJ succeeded in alleviating the biochemical and, to some extent, the histopathological changes induced by the high cholesterol diet. Consumption of fresh RGJ or its pharmaceutical preparations is advised especially for those who are used to eat a high fat diet.

Antioxidants protect against increased risk of atherosclerosis induced by exposure to cigarette smoke: Histological and biochemical study.

BACKGROUND AND OBJECTIVES: This study aimed to assess the dose-dependent effect of antioxidants in protection against cardiovascular changes induced by exposure to cigarette smoke. DESIGN AND SETTING: This was an experimental study, conducted at King Fahd Medical Research Center, King Abdulaziz University. MATERIALS AND METHODS: This study was carried out on 57 male albino rats divided into nine groups. Rats of experimental groups were exposed to cigarette smoke from a total of 100 cigarettes per week for four weeks in a specially designed chamber. The antioxidants used (vitamin C, E, and B-carotene) were administrated at low (9, 7.2, and 0.27 mg/day) and high doses (18, 14.4, and 0.54 mg/day), respectively, through gastric feeding tubes. The lipid profile was estimated, and the carotids and heart were removed, weighed, and then processed, and the carotid intima-media thickness was measured. Statistical analysis was performed using the Statistical Package for Social Sciences. RESULTS: The lipid profile was significantly improved in all groups treated with low or high doses of antioxidants after or during the exposure to cigarette smoke. Improvement was marked in the group treated with a high dose of antioxidants. The histological changes, as well as the intima-medial thickness of the carotid artery induced by exposure to cigarette smoke, have been improved by treatment with antioxidants (at either low or high doses), either after or during exposure to cigarette smoke. Improvement was marked in the group treated with a low dose of antioxidant. Treatment with antioxidants could not improve degenerated cardiac muscle fibers, while they could reduce the thickness of the branches of the coronary vessels. CONCLUSION: These results indicated that antioxidants ameliorated the cigarette smoke contribution to atherosclerosis, but they could not completely reverse the changes induced by cigarette smoke. Simultaneous intake of antioxidants could ameliorate the cigarette-smoke-induced changes apart from those of the heart.