scholarly journals Atypical Antipsychotic Lumateperone Effects on the Adrenal Gland With Possible Beneficial Effect of Quercetin Co-administration

2021 ◽  
Vol 12 ◽  
Author(s):  
Hala El-Haroun ◽  
Suzy Fayez Ewida ◽  
Wael M. Y. Mohamed ◽  
Manar Ali Bashandy
Keyword(s):  
Adrenal Gland ◽  
Atypical Antipsychotic ◽  
Animal Behavior ◽  
Animal Studies ◽  
Secretory Granules ◽  
Treated Group ◽  
Nuclear Antigen ◽  
End Of Treatment ◽  
Lipofuscin Pigment ◽  
Proliferating Cell

Schizophrenia remains one of the most chronic and highly disabling mental disorders. Lumateperone is a recent FDA-approved atypical antipsychotic drug for the treatment of schizophrenia. However, the internal FDA pathologist raised concerns regarding pigment deposition associated with degeneration in different tissue in animal studies with lumateperone treatment. The adrenal gland may be implicated in lumateperone side effects, and quercetin may have the ability to fulfill this treatment gap. To prove this hypothesis, 40 male guinea pigs were used and divided into four groups; control, quercetin-treated, lumateperone-treated, and quercetin/lumateperone cotreated orally for 28 consecutive days. Behavioral forced swim (FST) and open field (OF) tests were done at the end of treatment. Retro-orbital blood samples were taken to assess hormones: adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone acetate (DHEA), and aldosterone, along with an assessment of oxidative stress parameters: malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Adrenal glands were extracted for histopathological assessment with H&E, Mallory trichome staining, immunostaining, and electron microscopy studies. Lumateperone-treated group showed a significant reduction in the activity in FST and OF with histopathological deterioration in adrenal secretory function and structure and increased expression of interleukin-6 (IL-6), CASPASE-3, collagen deposition, and decreased proliferating cell nuclear antigen (PCNA). Cytoplasmic vacuolation, pyknosis of the nuclei, increase in the lysosome, lipofuscin pigment, and cellular infiltration with diminishing in the number of secretory granules could all be observed in lumateperone-treated group. Coadministration of quercetin and lumateperone showed improvement of the previously deteriorated parameters. Quercetin had a prophylactic effect against lumateperone depressive-like effect on animal behavior and its possible adrenal damage.Graphical AbstractConceptual framework for the proposed mechanism of action of coadministration of quercetin and lumateperone.

Effect of natural antioxidants and apocynin on LPS-induced endotoxemia in rabbit

2000 ◽  
Vol 19 (11) ◽  
pp. 604-614 ◽  
Author(s):  
V Ben-Shaul ◽  
L Lomnitskil ◽  
A Nyska ◽  
M Carbonatto ◽  
S Peano ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Proliferating Cell Nuclear Antigen ◽  
Immunohistochemical Staining ◽  
Microsomal Fraction ◽  
Natural Antioxidants ◽  
Treated Group ◽  
Nuclear Antigen ◽  
Sod Activity ◽  
Proliferative Effect ◽  
Proliferating Cell

The objective of this study was to compare the prophylactic effects of the natural antioxidant from spinach (NAO) and apocynin, on the hepatic oxidative stress and liver damage induced by lipopolysaccharide (LPS). Male New Zealand rabbits were challenged with LPS with or without 8 days of antioxidant pretreatment. Pretreatment with NAO, but not apocynin, significantly (p<0.05) decreased the levels of hydroperoxides and malondialdehyde (MDA) in the liver cytosolic fraction and the activity of NADPH oxidase-generated superoxide in the microsomal fraction, compared to LPS alone. The activity of glutathione peroxidase (G-POX) was significantly (p<0.05) increased in the LPS-treated group, whereas treatment with NAO, but not apocynin, significantly (p< 0.05) decreased G-POX activity. Pretreatment with the same antioxidants had no significant effects on superoxide dismutase (SOD) activity, whereas an increased level of catalase (CAT) was obtained in all LPS-treated groups. TUNEL immunohistochemical staining in the LPS-treated animals indicated that there was no increase in apoptosis outside of necrotic foci. However, apoptotic hepatocytes were observed within areas of focal necrosis in animals exposed to LPS alone or LPS plus apocynin. Hepatocyte cell proliferation was tested by the proliferating-cell nuclear antigen (PCNA) tool, which indicated a proliferative effect in the LPS group, whereas the effect disappeared in the antioxidant-treated groups. The prophylactic effect of NAO on liver pathology and the significant decreases in lipid peroxidation products and NADPH oxidase activity suggest the use of NAO as an efficient strategy for treatanent of endotoxemia.

scholarly journals Retinoic Acid Reduces Glomerular Injury in a Rat Model of Glomerular Damage

2000 ◽  
Vol 11 (8) ◽  
pp. 1479-1487 ◽  
Author(s):  
JÜRGEN WAGNER ◽  
CLAUDIUS DECHOW ◽  
CHRISTIAN MORATH ◽  
INGO LEHRKE ◽  
KERSTIN AMANN ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Rat Model ◽  
Proliferating Cell Nuclear Antigen ◽  
Treated Group ◽  
Nuclear Antigen ◽  
Control Group ◽  
Glomerular Injury ◽  
Proliferating Cell ◽  
Vehicle Treated Group ◽  
Glomerular Damage

Abstract.In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n= 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol,i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 ± 4.8 mmHg; anti-Thy1.1/RA, 87.5 ± 2.5 mmHg;P< 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P< 0.02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 ± 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 ± 4.4;P< 0.02; control/vehicle, 69 ± 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 ± 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 ± 0.5,P< 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 ± 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 ± 0.8 cells were proliferating cell nuclear antigen-positive (P< 0.002; control, 2.2 ± 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1.1/RA-treated group, compared with the anti-Thy1.1/control group (P< 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P< 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.

Melatonin Elicits Stimulatory Action on the Adrenal Gland of Soay Ram: Morphometrical, Immunohistochemical, and Ultrastructural Study

2017 ◽  
Vol 23 (6) ◽  
pp. 1173-1188 ◽  
Author(s):  
Doaa M. Mokhtar ◽  
Manal T. Hussein ◽  
Ahmed H. S. Hassan
Keyword(s):  
Endoplasmic Reticulum ◽  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Chromaffin Cells ◽  
Adrenal Glands ◽  
Secretory Granules ◽  
Treated Group ◽  
Nerve Fibers ◽  
Melatonin Treatment ◽  
Stimulatory Action

AbstractEndogenous melatonin is a hormone secreted by pineal gland; it has several roles in metabolism, reproduction, and remarkable antioxidant properties. Studies on the melatonin effect on the adrenal glands which are important endocrine organs, controlling essential physiological functions, are still deficient. In this study, we attempted to investigate the effect of exogenous melatonin treatment on the adrenal cortex and medulla using several approaches. Adrenal glands of 15 Soay ram were examined to detect the effect of melatonin treatment. Our results revealed that the cells of adrenal cortex of the treated animals were separated by wide and numerous blood sinusoids and showed signs of increase steroidogenic activity, which are evidenced by functional hypertrophy with increase profiles of mitochondria, smooth endoplasmic reticulum, and lipid droplets. The most striking ultrastructural features in the medulla of the treated group were the engorgement of chromaffin cells with enlarged secretory granules enclosed within a significantly increased diameter of these cells. The cytoplasm of these cells showed numerous mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus, lysosomes, and glycogen granules. Exocytosis of secretory granules to the lumen of blood vessels was evident in the treated group. Piecemeal degranulation mode of secretion was recorded after melatonin treatment. Chromaffin cells in the control group expressed moderate immunoreactivity to Synaptophysin and tyrosine hydroxylase, compared with intensified expression after melatonin treatment. The ganglion cells of the melatonin-treated group showed a significant increase in diameter with numerous rER. The most interesting feature in this study is the presence of small granule chromaffin cells (SGC) and telocytes (TCs) for the first time in the adrenal glands of sheep. Moreover, these SGC cells, Schwann cells, fibroblasts, and progenitor stem cells showed a stimulatory response. The TCs were small branched cells scattered in the adrenal glands around cortical cells, chromaffin cells, nerve fibers, and blood vessels. These cells increased significantly in number, length of their telopodes, and secretory activity after melatonin treatment. In addition, multiple profiles of unmyelinated nerve fibers were demonstrated in all treated specimens. These results indicated that melatonin treatment caused a stimulatory action on all cellular and neuronal elements of the adrenal gland. This study may act as a new direction for treatment of adrenal insufficiency.

scholarly journals Proliferating cell nuclear antigen antibody testing – getting them all

Pathology ◽  
2021 ◽  
Vol 53 ◽  
pp. S47
Author(s):  
Christine Bundell ◽  
Mathew Krummenacher ◽  
Elina Tan ◽  
Paul Sjollema ◽  
Nick Acquarola ◽  
...  
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Antibody Testing ◽  
Antigen Antibody ◽  
Proliferating Cell
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