ABSTRACT
Aspartame (ASP) is an artificial sweeter. Chronic use of ASP has a harmful effect on cerebellar cortex. Anisum oil and selenium (SE) are antioxidant substances. Therefore, the present study was performed to study the possible protective role of anisum oil versus selenium on aspartame-induced changes in rat cerebellar cortex. Rats were divided into four main groups. Group I (Control group). Group II received 250 mg/kg/day aspartame once daily for 2 months. Group III received 0.5 ml/kg/day anisum 2 h before aspartame administration. Group IV received 0.5 mg/kg/day selenium 2 h before aspartame administration. The administration of Asp for 2 months (group II) resulted in cerebellar histopathological changes in the form of deformed Purkinje and granule cells. Ultrastructurally, Purkinje cells had irregular nuclei, dilated cisternae of rough endoplasmic reticulum, dilated saccules of Golgi apparatus, mitochondria with destroyed cristae. In addition, granule cells appeared shrunken with irregular nuclei. Aspartame and anisum oil treated group (group III) showed partial improvement. Examination of ASP and SE treated group (group IV) showed that cerebellar cortex was nearly similar to control. In conclusion, Anisum oil and selenium could protect against ASP-induced cerebellar damage. The protective effect of selenium is better than anisum oil.
Subject(s)
Pimpinella , Selenium , Rats , Animals , Aspartame/toxicity , Selenium/pharmacology , Electrons , Pimpinella/chemistry , Cerebellar CortexABSTRACT
Empagliflozin (EMPA) is a promising novel antidiabetic drug; however, doubts have been raised regarding its use and the increased risk of urinary bladder carcinoma. In this study, we evaluated urothelium expression of cytokeratins (CKs) and Ki-67 proliferative activity in the urinary bladder of diabetic (DM + EMPA) and non-diabetic rats after EMPA administration. By routine histology, dysplastic changes were detected in the urothelium of diabetic as well as non-diabetic animals after EMPA administration. Moreover, the expression of CK-7 and CK-8 was significantly decreased (P < .05) while that of CK-20 as well as Ki-67 was significantly increased (P < .05) in EMPA per se and DM + EMPA urothelium groups compared to that of control and diabetics. The dysplastic changes together with the increased proliferative activity in urothelium after EMPA administration provide a cellular evidence that supports the former clinical concerns.
Subject(s)
Benzhydryl Compounds/adverse effects , Diabetes Mellitus, Experimental/drug therapy , Glucosides/adverse effects , Hypoglycemic Agents/adverse effects , Urinary Bladder/drug effects , Urothelium/drug effects , Animals , Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Experimental/pathology , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Male , Rats , Rats, Sprague-Dawley , Urinary Bladder/pathology , Urothelium/pathologyABSTRACT
Although there is emerging evidence that mast cells are involved in infertility, their exact role has not been elucidated clearly. Here we carried out a retrospective case-control study to find out whether there is a correlation between mast cell (MC) count and proliferation (Ki67 index) of the spermatogenic epithelium as well as of the Sertoli cells (vimentin-positive) in non-obstructive azoospermia (NOA). We assessed MCs, Ki67 and vimentin expression in Sertoli cells in testicular biopsies of germ cell aplasia (GCA, n = 14) and maturation arrest (MA, n = 14) vs. normal spermatogenesis (n = 14) cases. There was a significant decrease in the spermatogonial Ki67 index (1.25 ± 0.91, 4.21 ± 1.81 vs. 39.57 ± 3.92) and Johnsen score (2.48 ± 0.65, 4.89 ± 1.05 vs. 9.75 ± 0.30) as well as a significant increase (P < 0.001) in MC count (29.00 ± 4.11, 7.57 ± 1.95 vs. 3.00 ± 1.30) in seminiferous tubules of infertile cases with GCA and MA vs. controls. On the other hand, the percentage of vimentin-expressing Sertoli cells was significantly decreased (P < 0.001) in biopsies of cases with MA (35.50 ± 15.62) compared to those of cases with GCA and controls (72.64 ± 10.67 and 98.57 ± 1.45 respectively). Additionally, a significant negative correlation was detected between MC count and Ki67 index as well as Johnsen score in the MA group which became more significant in the GCA group. The significant increase in MC count in the GCA group and to a lesser extent in the MA group indicates their possible role in NOA particularly at the spermatogonial proliferation level and this is supported by the significant negative correlation with the Ki67 index.
Subject(s)
Azoospermia/pathology , Mast Cells/pathology , Sertoli Cells/pathology , Spermatogenesis , Spermatozoa/pathology , Testis/pathology , Azoospermia/metabolism , Azoospermia/physiopathology , Biopsy , Cell Proliferation , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Male , Retrospective Studies , Sertoli Cells/chemistry , Testis/chemistry , Testis/physiopathology , Vimentin/analysisABSTRACT
BACKGROUND: ART is steadily performed for infertility cases and most of the previous researches have focused on complicated pregnancies. Nonetheless, few ones have concerned with placenta of ART in non-complicated pregnancies. OBJECTIVES: To investigate the expression of angiopoietins (ANG) and their receptor, TIE-2, in placenta of full-term non-complicated pregnancies having ART (n=28) versus those with spontaneous conception (n=28) together with the histological as well as morphometric analysis. RESULTS: While no prominent changes were noticed in the histological structure of the placenta ART pregnancies, it showed a significant decrease (p<0.05) in the percentage of syncytial area and numbers of syncytial knots with insignificant reduction in the placental villous area. Vascular changes in the form of significant decrease (p<0.05) in the chorionic vessel diameter and significant increase (p<0.05) in percentage of vessel area were detected in the ART placenta. In addition, the levels ANG-1, ANG-2 and TIE-2 were significantly increased (p<0.05) in the ART placentas compared with those of SC. CONCLUSIONS: We demonstrated that there is an altered expression of angiopoietins accompanying the morphometric changes occurring in placenta of ART pregnancies. These changes may indicate vascular and cellular adaptation mechanism for a potential subclinical hypoxia in placenta of ART even in non-complicated pregnancies.
Subject(s)
Angiopoietin-1/metabolism , Angiopoietin-2/metabolism , Placenta/blood supply , Placenta/metabolism , Reproductive Techniques, Assisted , Angiopoietin-1/genetics , Angiopoietin-2/genetics , Case-Control Studies , Female , Gene Expression Regulation , Humans , Ki-67 Antigen/metabolism , Microscopy, Electron, Scanning , Pregnancy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, TIE-2/genetics , Receptor, TIE-2/metabolismABSTRACT
Letrozole (LTZ), one of the ovulation induction medications, is increasingly prescribed in various gynaecological conditions. Previous studies have demonstrated its potential hazardous effect on the ovarian surface epithelium (OSE) as well as on tubal epithelial cells (TEC). However, it is not clear whether this effect could be reversed by LTZ cessation. Therefore, the objective of our study was to investigate the effect of stoppage of LTZ on these cells after 12 cycles of ovarian stimulation. A total of 54 Sprague Dawley rats were used in this study, divided equally into control, LTZ12 and CES12 groups (received saline, 12 cycles of LTZ and 12 cycles of cessation post-LTZ12 respectively). Samples from the ovaries as well as fallopian tubes (FTs) were studied histologically for the changes associated with LTZ12 and CES12 respectively. There was evident increase in the proliferative activity and Ki67 immunoexpression in the OSE of LTZ12. The OSE was hyperchromatic, and abnormally frequent deep invaginations, micropapillae and cortical cysts. Their TEC showed frequent multilayering, papillary projections and loss of cilia. Almost all these changes disappeared 12 cycles after LTZ cessation. While the tubal IL-1ß, IL-6, TNF-α and serum MCP-1 levels significantly increased in the LTZ12 group compared with the control group, their levels decreased in the CES12 group compared with those of the control. Therefore, the abnormal tubo-ovarian epithelial patterns may completely regress after cessation of LTZ stimulation for a reasonable duration. This is a potentially good omen and a positive indicator of the relatively safe use of LTZ after its intake has been stopped.
Subject(s)
Aromatase Inhibitors/pharmacology , Fallopian Tubes/drug effects , Nitriles/pharmacology , Ovary/drug effects , Ovulation Induction/methods , Triazoles/pharmacology , Animals , Cell Proliferation/drug effects , Chemokine CCL2/blood , Cytokines/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelium/drug effects , Epithelium/metabolism , Epithelium/pathology , Fallopian Tubes/metabolism , Fallopian Tubes/pathology , Female , Letrozole , Ovary/metabolism , Ovary/pathology , Rats, Sprague-Dawley , Withholding TreatmentABSTRACT
BACKGROUND AND AIM: The use of BioEnterics intragastric balloon (BIB) is progressively increasing, owing to the fact that morbid obesity becomes a global epidemic together with risks of bariatric surgery. Yet, the possible local BIB effect on gastric mucosa is not clearly elucidated. The aim of the current study was to assess the histological changes occurring in the gastric mucosa post-BIB insertion. METHODS: Gastric mucosa biopsy was obtained from 87 cases of morbid obesity both pre-BIB and 6 months post-BIB insertion to compare the local changes by histological and immunohistochemical analysis. RESULTS: An inflammatory reaction was detected in the post-BIB mucosa which displayed a positive CD20, CD3 (p < 0.05), and the proliferation index (Ki67) increased significantly compared with that of the pre-BIB cases. The Ki67 index showed a significant positive correlation with CD20 and CD3 immunoexpression in the post-BIB gastric mucosae. CONCLUSION: Our results demonstrated a possible increase in the gastric proliferative activity after BIB insertion accompanied with a remarkable local inflammatory reaction. Although these findings may be reactive and transient, endoscopic follow-up is recommended for early detection of further pathological changes.
Subject(s)
Antigens, CD20/immunology , Bariatric Surgery , CD3 Complex/immunology , Gastric Balloon , Gastric Mucosa/immunology , Ki-67 Antigen/metabolism , Obesity, Morbid/surgery , Pyloric Antrum/immunology , Adult , Cell Proliferation , Female , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Humans , Immunohistochemistry , Inflammation , Male , Middle Aged , Pyloric Antrum/metabolism , Pyloric Antrum/pathology , Retrospective StudiesABSTRACT
Objective: The objective of the study is to investigate changes occurring in key inflammatory cytokines at molecular level (including genetic and protein) in placental bed of placenta creta compared to that of normal placenta and their correlation to interstitial extravillous trophoblasts (EVT) number. Subjects and Methods: Case-control study including placentas of patients with invasive placentation (creta placentas, n = 19) compared with those of normal placentation (n = 19). Besides routine histology and immunocytochemistry detection (cytokeratin-7 [CK-7]), addition to biochemical evaluation of expression of various cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), IL6, IL-1RA, IL-8, IL-10, and IL-13 was carried out. Results: Routine histological examination of placentas of creta cases revealed CK-7+ extravillous trophoblasts (EVT) penetrating deeply the myometrium with various histopathological arrangements and trophoblastic vascular invasion of the deep myometrial blood vessels. A significant increase (P < 0.05) in the mRNA expression of TNF-α, IL-1 ß, and IL6 with an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 was observed in creta cases compared to the control ones. A corresponding significant increase was detected in the protein levels of TNF-α, IL-1 ß, and IL-6 as well as an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 in creta cases compared to the normal ones. Moreover, we displayed a significant positive correlation (P < 0.05) between interstitial EVT number and mRNA expression of almost all pro-inflammatory cytokines with negative but insignificant correlation with anti-inflammatory cytokines in creta cases. Conclusion: The upregulated pro-inflammatory cytokines and the correlation of their expression with the increased interstitial EVT provide a supporting evidence of their potentially more relevant role in the development of placenta creta than the anti-inflammatory ones.
ABSTRACT
Objectives: Pioglitazone (PIO) is a widely prescribed oral antidiabetic drug that has concerns regarding a potential risk of developing carcinoma of the urinary bladder. The objective of the current study was to assess this potential risk. Materials and Methods: The potential risk of PIO-induced urinary bladder carcinoma was assessed in the current study by examining urinary bladder of rats for urothelial cytokeratin (CK) expression and proliferative activity by Ki67 immunostaining. Results: Histological examination revealed dysplastic urothelial changes in PIO per se and diabetes mellitus + PIO (diabetic rats receiving PIO). In addition, a significantly (P < 0.05) decreased CK7 and CK8 expression together with a significantly increased CK20 as well as Ki67 expression was detected in the urothelial cells of groups administrated PIO, contrary to those which did not. Conclusion: The manifestations of urothelial dysplasia evidenced by histological examination as well as by the aberrant expression in CK and Ki67 after PIO administration add supporting evidence at cellular and experimental level to the previous clinical suspicions.
ABSTRACT
The effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on myocardium in diabetic cardiomyopathy (DCM) remains a matter of debate. In the current study we investigated the effect of vildagliptin (VILDA, 3 mg/kg/d) on myocardium of DCM focusing on coronary microcirculation as well as on endothelial stress markers (ICAM and VCAM). We divided animals equally into 4 groups; nondiabetic (ND), VILDA per se, DCM and DCM + VILDA and their myocardium was evaluated for the fibro-vascular remodeling immunohistochemically as well as for molecular changes. VILDA had reversed the histological changes occurred in DCM including the disintegration, degeneration, and steatosis of cardiomyocytes with disappearance of the edema fluid. In addition VILDA significantly increased (p < 0.05) density of the coronary microcirculation and relieved endothelial stress. However, it did not prevent the development of fibrotic remodeling including the increased collagen deposition and the significantly upregulated (p < 0.05) corresponding genes. Therefore VILDA may have a positive impact on the microvascular remodeling, but not on fibrotic changes, in DCM.
Subject(s)
Diabetic Cardiomyopathies/pathology , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Myocardium/pathology , Vildagliptin/pharmacology , Animals , Diabetes Mellitus/drug therapy , Fibrosis/drug therapy , Fibrosis/pathology , Hypoglycemic Agents/pharmacology , Myocytes, Cardiac/drug effects , Nitriles/pharmacologyABSTRACT
Liraglutide is a new therapy used in diabetes and its effect on diabetic complications particularly cardiovascular ones is still under investigated. In our research, we tried to study the effect of liraglutide on experimental diabetic cardiomyopathy (DCM) induced by streptozotocin. We found that liraglutide nearly preserved normal myocardiac structure and significantly protected against myocardiac inflammation and fibrosis that was found in DCM group, p < 0.05. It also increased the density of coronary arteriolar vasculature markedly indicated by significant increase in α SMA (p < 0.05) compared to both DCM and non-diabetic (ND) groups. Moreover, liraglutide decreased TNFα and increased VEGF proteins expression (P < 0.05) compared to DCM group. Conclusion, liraglutide may have a very important role in protecting against experimentally induced diabetic cardiomyopathy by preventing the degenerative changes in the cardiomyocytes and the associated fibrosis, inflammation and decreased vasculature at structural and molecular levels.
Subject(s)
Diabetic Cardiomyopathies/physiopathology , Hypoglycemic Agents/pharmacology , Liraglutide/pharmacology , Microcirculation/drug effects , Actins/metabolism , Animals , Blood Glucose/metabolism , Coronary Vessels/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/pathology , Endomyocardial Fibrosis/drug therapy , Endomyocardial Fibrosis/pathology , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Myocarditis/drug therapy , Myocarditis/pathology , Neovascularization, Pathologic/drug therapy , Rats , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The role of mast cells (MCs) in prediabetes (Pre-DM) is not clearly elucidated. In the current study rats (n = 22 each) were divided equally into; control and Pre-DM (received high fat diet, HFD) groups. Samples from pancreas as well as from visceral adipose tissue (VAT) were studied for the consequent changes. We detected a significantly increased mast cell count (MCC) in the pancreas of Pre-DM compared to that of control. Frequent degranulation of MC granules was observed in Pre-DM. VAT of the Pre-DM had significantly increased (p < 0.05) macrophages (CD68+) and mast cells (tryptase+) compared to that of the control. A significant increase (p < 0.05) in CD68 mRNA expression as well as in the level of IL-1 ß, IL-6, TNF-α and TGF- ß1 was detected in VAT of Pre-DM with a significant positive correlation (p < 0.05) with the MCC. All these findings may indicate a potential role of MC in the low grade inflammation of VAT in Pre-DM.
Subject(s)
Intra-Abdominal Fat , Mast Cells/pathology , Pancreas , Prediabetic State , Animals , Cell Proliferation , Diet, High-Fat , Inflammation , Insulin-Secreting Cells/pathology , Intra-Abdominal Fat/immunology , Male , Pancreas/immunology , Prediabetic State/chemically induced , Rats , Real-Time Polymerase Chain Reaction , Reference StandardsABSTRACT
The role of mast cells (MCs) in type 2 diabetes (T2D) is not thoroughly studied as much as in T1D. Therefore in the current study we investigated correlation between these cells and various parameters of islets of Langerhans (IOL) in rats which were equally divided (n = 40) into; control and diabetic groups. We detected a significantly increased (p < 0.05) MC count (MCC) in the diabetic IOL compared to the control, together with a noticeable intra-islet seeding of these cells which displayed a tryptase positive immunostaining. A significant positive correlation (p < 0.05) between MCC and the % of glucagon cells per islet was detected in DM, unlike mass of the islets, mass of ß-cells, and % of ß-cells per islet which were negatively correlated with MCC. Similarly, there was a negative correlation between MCC with ß-cell proliferation and neogenesis frequency in DM. This highlights the potential association between the increased MC number and the diminished islet`s mass as well as regeneration which may fasten the progression of T2D.
Subject(s)
Diabetes Mellitus, Type 2/pathology , Glucagon-Secreting Cells/physiology , Insulin-Secreting Cells/physiology , Animals , Cell Proliferation/physiology , Glucagon-Secreting Cells/pathology , Immunohistochemistry , Insulin-Secreting Cells/pathology , Male , Mast Cells , Rats , Rats, Sprague-Dawley , Tryptases/metabolismABSTRACT
The effect of empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on the structure of endocrine pancreas in pre-diabetes (Pre-DM) is not yet elucidated. In the current study the relatively enlarged islets of Langerhans seen in the Pre-DM group was restored to control size by administration of EMPA. In addition the disbalance in the percentage of ß-cells and α-cells in islets of the Pre-DM was corrected in the Pre-DMâ¯+â¯EMPA group with reversal of the significantly increased islet mass, ß-cell mass and neogenesis. Administrating EMPA in Pre-DM decreased level of caspase-3, increased that of Bcl-2 to control level and reduced the significantly increased inflammatory cytokines to levels approximated to those of the control group. In Pre-DMâ¯+â¯EMPA group, EMPA had efficiently restored the significantly impaired glucose hemostasis to levels nearly similar to those of the control animals. This may indicate that the modulatory effect of EMPA on cells of the islets in Pre-DM is associated with a local pleotropic effect on inflammatory cytokines.
Subject(s)
Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Experimental/pathology , Glucosides/therapeutic use , Islets of Langerhans/drug effects , Prediabetic State/pathology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Animals , Area Under Curve , Benzhydryl Compounds/pharmacology , Blood Glucose/drug effects , Blood Glucose/metabolism , Caspase 3/drug effects , Caspase 3/metabolism , Cell Proliferation , Cytokines/drug effects , Cytokines/metabolism , Diabetes Mellitus, Experimental/drug therapy , Glucagon/blood , Glucagon-Secreting Cells/cytology , Glucagon-Secreting Cells/drug effects , Glucose Tolerance Test , Glucosides/pharmacology , Homeostasis , Immunohistochemistry , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Islets of Langerhans/cytology , Islets of Langerhans/pathology , Male , Prediabetic State/drug therapy , Proto-Oncogene Proteins c-bcl-2/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , Sodium-Glucose Transporter 2 Inhibitors/pharmacologyABSTRACT
Although metformin is widely prescribed in diabetes, its use with associated cardiac dysfunction remains debatable. In the current study, we investigated the effect of metformin on coronary microvasculature in experimental diabetic cardiomyopathy (DCM) induced by streptozotocin. Administration of metformin after induction of DCM, reversed almost all cardiomyocyte degenerative changes induced by DCM. Metformin diminished the significantly increased (p < 0.05) collagen deposited in the DCM. In addition metformin had improved the density of the significantly decreased arteriolar (αSMA+) and capillary (CD31+) coronary microvasculature compared to that of the DCM and non-diabetics (ND) with downregulation of the significantly increased expression (p < 0.05) of COL-I, III, TGF-ß, CTGF, ICAM and VCAM genes. Therefore metformin may be beneficial in limiting the fibrotic and the vascular remodeling occurring in DCM at the genetic as well as the structural levels.
Subject(s)
Diabetic Cardiomyopathies/drug therapy , Metformin/pharmacology , Microvessels/drug effects , Animals , Coronary Vessels , Disease Models, Animal , Fibrosis/drug therapy , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Streptozocin , Vascular Remodeling/drug effectsABSTRACT
Letrozole (LTZ), one of ovulation induction medications, is increasingly prescribed in many gynecological conditions. Although its hazardous effect on the ovarian surface epithelium (OSE) as well as tubal epithelium cells (TEC) has been previously studied, the associated changes occurring in the inflammatory cytokines have not been elucidated. Therefore, the objective of our study is to investigate these changes that may accompany LTZ-induced tubo-ovarian epithelial abnormalities. A total of 45 Sprague-Dawley rats were used in this study, divided equally into; control, LTZ6 and LTZ12 groups (received saline, 6 and 12 cycles LTZ i.p. respectively). Samples from ovaries (OVs) as well as fallopian tubes (FTs) were histologically studied for the associated changes. An increased proliferative activity, Ki67 immunoexpression and abnormal invaginations were observed in the OSE of LTZ6 group accompanied with occasional pseudostratification and loss of cilia of TEC. These changes became more pronounced in the LTZ12 where micropapillae, hyperchromasia, frequent deep invaginations, cysts of OSE as well as papillae and multilayering of TEC were noticed. The tubal level of IL-1ß, IL-6, TNF-α and serum MCP-1 progressively increased in LTZ6 and LTZ12 groups compared with the control group. The significant positive correlation observed between these cytokines in the LTZ6 group became stronger in the LTZ12 one. However, no significant changes in the tubal IL-10 and TGF-ß were detected. Therefore, further studies are required to consider these cytokines as objective markers to precisely assess severity of the associated epithelial changes particularly in long periods of stimulation.
Subject(s)
Aromatase Inhibitors/pharmacology , Fallopian Tubes/metabolism , Interleukins/metabolism , Nitriles/pharmacology , Ovary/cytology , Triazoles/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Animals , Chemokine CCL2/blood , Epithelium/drug effects , Epithelium/metabolism , Fallopian Tubes/drug effects , Female , Letrozole , Ovary/drug effects , Rats , Rats, Sprague-DawleyABSTRACT
Hydroxychloroquine (HCQ) is supposed to have favorable effects in diabetes mellitus (DM). However no previous experimental studies had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in DM. In addition, the mechanism by which HCQ acts in DM is not well understood. In this study, we hypothesized that the possible favorable effects of HCQ in DM at the structural as well as at metabolic levels could be accomplished, in part, by its anti-inflammatory action. A total of 45 rats were divided equally into; control, DM and HCQ + DM groups (received citrate buffer, 27.5 mg/kg single ip STZ and STZ + HCQ 200 mg/kg/w respectively). After 4 weeks, samples from pancreas were histologically studied for the resulting changes. The HCQ + DM group showed preservation of IOL structure, a significant increase (p < 0.05) in the ß-cell area, %, mass, IOL proliferation and neogenesis as well as correction of the significantly increased (p < 0.05) α-cell area, %, disturbed glucose homeostasis and lipid profile compared with the DM group. The significantly elevated inflammatory cytokines in the latter were lowered in the HCQ + DM group. Therefore, HCQ showed definite favorable effects on the histological as well as the metabolic profiles in DM which may be partly attributed to its anti-inflammatory action. This notable improvement of DM by HCQ deserves further studies to distinctly approve HCQ as a promising oral hypoglycemic agent.
Subject(s)
Cytokines/metabolism , Diabetes Mellitus, Experimental/pathology , Hydroxychloroquine/pharmacology , Inflammation Mediators/metabolism , Islets of Langerhans/pathology , Animals , Biomarkers/blood , Caspase 3/metabolism , Diabetes Mellitus, Experimental/blood , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Islets of Langerhans/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats, Sprague-DawleyABSTRACT
Hydroxychloroquine (HCQ) has been demonstrated to reduce the risk to develop diabetes mellitus (DM). However no previous experimental study had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in insulin resistance (IR). In addition, the mechanism by which HCQ can prevent DM is not well understood. In this study, we hypothesized that the possible favorable outcome of HCQ may be partly achieved by its molecular effect on the endothelial stress markers as well as on the imparied balance of the adipokines that usually accompanies IR. A total of 54 rats were divided equally into; control, high fat diet (HFD) and HFD+HCQ groups (received standard chow, HFD and HFD+HCQ respectively). After 12 weeks, samples from pancreas as well as visceral adipose tissue (VAT) were histologically studied for the consequent changes. In the HFD group, there were mild degenerative changes and expansion of the IOL accompanied with a significantly increased (p<0.05) ß-cell area%, mass, proliferation and neogenesis as well as a significantly decreased (p<0.05) α-cell area% compared with the other groups. On combining HCQ with HFD, reversal of these changes along with correction of the impaired adipokines levels (leptin, adiponectin, resistin, visfatin and lipocalin-2) and significant decrease (p<0.05) of the vascular endothelial stress markers (sE-selectin, sICAM and sVICAM) were manifested compared with the HFD group. Therefore, HCQ favorable effects in IR may be attributed to relieving of the endothelial stress as well as normalization of the skewed balance of adipokines.
Subject(s)
Adipokines/metabolism , Endothelial Cells/drug effects , Hydroxychloroquine/pharmacology , Insulin Resistance/physiology , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/metabolism , Islets of Langerhans/drug effects , Animals , Diet, High-Fat , Endothelial Cells/metabolism , Insulin-Secreting Cells/drug effects , Leptin/metabolism , Male , Nicotinamide Phosphoribosyltransferase/metabolism , Obesity/drug therapy , Obesity/metabolism , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate changes occurring in the morphometric parameters of chorionic villi and their vessels as well as in adhesive molecules expression in placenta of ART pregnancies. METHODS: Case-control study including a total of 52 placentas of non-complicated pregnancies of women delivered by spontaneous conception (SC) (n = 26) compared with those of ART (n = 26). Histological and morphometric assessment of fetal chorionic villi as well as the expression of various adhesive molecules (ICAM-1, VCAM-1 and PECAM-1) were performed in fetal plasma and placenta. RESULTS: Although we did not observe any obvious changes in the histological structure of placenta of ART pregnancies, it showed a significant (p < 0.05) decrease in the syncytiotrophoblast cytoplasmic area accompanied with a significant increase (p < 0.05) in the vessel area and syncytiotrophoblast nuclear area without remarkable change in the total villous area or total syncytiotrophoblast % area. In addition, almost all levels of the assayed adhesive molecules were significantly increased (p < 0.05) in placenta as well as in fetal plasma of ART pregnancies compared with SC. CONCLUSION: We suggested in the current study that the altered adhesive molecules expression accompanying the increased vessel area and decreased syncytial cytoplasm area may indicate a subclinical endothelial stress in placenta of non-complicated ART pregnancies.
Subject(s)
Chorionic Villi/metabolism , Intercellular Adhesion Molecule-1/metabolism , Placenta/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Reproductive Techniques, Assisted , Vascular Cell Adhesion Molecule-1/metabolism , Adult , Case-Control Studies , Chorionic Villi/anatomy & histology , Female , Humans , Placenta/anatomy & histology , Pregnancy , Trophoblasts/metabolismABSTRACT
Ethambutol (ETM)-induced retinal injury is associated with a deterioration in visual function caused by a mechanism similar to many other retinal injuries; i.e. glutamate-induced N-methyl-d-aspartate (NMDA) receptor hyperexitability. Therefore, the current study was carried out to investigate the effect of memantine (MEM), NMDA receptor blocker, on ETM-induced retinal injury. A total of 36 rats were divided equally into: group I, control, group II (ETM administration, 100mg/kg/d, orally for 4 weeks) and group III (administration of ETM+MEM, 100 and 5mg/kg/d, respectively, orally for 4 weeks). Specimens of the retina were prepared for histological study by haematoxylin, eosin (H&E) as well as for immunohistochemical study by Bcl-2, cleaved caspase-3 and glial fibrillary acidic protein (GFAP). In the ETM group, the neural retina became significantly thinner (p<0.05) and the ganglion cell layer (GCL) was the main layer affected in the form of a significant decrease (p<0.001) in its cellularity, along with an obvious increase in Bcl-2 and GFAP expression as well as caspase-3 and oxidative stress markers level compared with other groups. On the other hand, on combining MEM with ETM, the retinal thickness, NFL appearance and GCL cellularity returned to amounts nearly similar to the control group coupled with a significant decrease (p<0.05) in the detected caspase-3, Bcl-2 levels and minimal GFAP expression. Therefore, memantine could be an effective neuroprotective agent in ETM-induced retinal injury by a mechanism that may involve correction of the pro/anti-apoptotic pathways and normalization of the oxidative and Müller cell stress responses.
Subject(s)
Ethambutol , Excitatory Amino Acid Antagonists/therapeutic use , Memantine/therapeutic use , Neuroprotective Agents/therapeutic use , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Retinal Perforations/chemically induced , Retinal Perforations/drug therapy , Animals , Caspase 3/biosynthesis , Caspase 3/genetics , Glial Fibrillary Acidic Protein/metabolism , Immunohistochemistry , Male , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/genetics , Rats , Rats, Sprague-Dawley , Retina/pathology , Retinal Perforations/pathologyABSTRACT
Diabetic hazard on the myocardium is a complication of diabetes that intensifies its morbidity and increases its mortality. Therefore, alleviation of diabetic cardiomyopathy (DCM) by a reliable drug remains a matter of interest in experimental research. The aim of this study was to explore the structural alterations in the myocardium induced by atorvastatin (ATOR) in DCM, induced by streptozotocin (STZ), along with the associated changes occurring in apoptosis and oxidative stress markers. Thirty-two rats were divided into four groups; group A (control), group B (non-diabetic, received ATOR, orally, 50 mg/kg daily), group C (DCM, received STZ 70 mg/kg, single i.p. injection) and group D (DCM + ATOR). After 6 weeks, left ventricle (LV) specimens were prepared for histological and immunohistochemical study by hematoxlyin and eosin, Masson`s trichrome, anti-cleaved caspase-3 stains as well as for assays of oxidative stress markers. All data were measured morphometrically and statistically analyzed. The DCM group showed disorganization of the cardiomyocytes, interstitial edema, numerous fibroblasts, significant increases in the collagen volume fraction (p < 0.001), cleaved caspase-3 expression % area (p < 0.001) and, malondialdehyde in blood (p < 0.001), in LV (p < 0.05) compared with DCM + ATOR group. The latter has LV wall thickness, relative heart weight and antioxidant activities nearly similar to the control, independent from ATOR lipid-lowering effect. Therefore, ATOR can preserve myocardial structure in DCM nearly similar to normal. This may be achieved by suppressing apoptosis that parallels the correction of the antioxidant markers, which can be considered as non-lipid lowering benefit of statins.