scholarly journals Melatonin Increases Bone Mass around the Prostheses of OVX Rats by Ameliorating Mitochondrial Oxidative Stress via the SIRT3/SOD2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Wei Zhou ◽  
Yu Liu ◽  
Jining Shen ◽  
Binqing Yu ◽  
Jiaxiang Bai ◽  
...  

Bone mass loss around prostheses is a major cause of implant failure, especially in postmenopausal osteoporosis patients. In osteoporosis, excess oxidative stress largely contributed abnormal bone remodeling. Melatonin, which is synthesized from the pineal gland, promotes osteoblast differentiation and bone formation and has effectively been used to combat oxidative stress. Thus, we determined if melatonin can inhibit oxidative stress to promote osteogenesis and improve bone mass around prostheses in osteoporosis. In this study, we observed that received melatonin at 50 mg/kg body weight significantly increased periprosthetic bone mass as well as implant fixation intensity in ovariectomized (OVX) rats. Meanwhile, it decreased the expression of oxidative stress markers (NAPDH oxidase 2 and cytochrome c) and enhanced expressing level of the formation markers of bones (alkaline phosphatase, osteocalcin, and osterix) around prostheses compared to that in the control group. Additionally, melatonin decreased hydrogen peroxide- (H2O2-) induced oxidative stress and restored the osteogenesis potential of MC3T3-E1 cells. Mechanistically, melatonin clearly increased mitochondrial sirtuin 3 (SIRT3) expression and decreased the ratio of acetylated superoxide dismutase 2 (AC-SOD2)/SOD2 compared to the H2O2 group. SIRT3 inhibition counteracted the protective effects of melatonin on oxidative stress and bone formation. Together, the results showed that melatonin ameliorated oxidative stress in mitochondrial via the SIRT3/SOD2 signaling pathway, thereby promoting osteogenesis, improving bone mass around the prostheses, and increasing initial stability. Thus, melatonin might be a suitable candidate to decrease the rate of implant failure and lengthen the lifespan of prostheses after total joint arthroplasty.

2007 ◽  
Vol 35 (01) ◽  
pp. 89-101 ◽  
Author(s):  
Wenping Zhang ◽  
Masayuki Kanehara ◽  
Yanjun Zhang ◽  
Xiaoming Wang ◽  
Torao Ishida

We investigated whether treatments with beta-blockers or other administrations that have similar actions to β-blockers, such as Chinese herbs or needling, were effective in treating osteoporosis induced by ovariectomy (OVX). Female Wister rats were divided into five groups: a sham-operated control group treated with vehicle (Sham, n = 8), an ovariectomized (OVX) group treated with vehicle (Model, n = 8), an OVX group administered with propranolol (Pro, n = 10), an OVX group administered an ethanol extract of Fructus Citri Sarcodactylis (Fcs, n = 9), and an OVX punctured at Sanyinjiao (SP-6) and Neiguan (PC-6) (Needling, n = 8). The treatment started when rats were 12 weeks old and continued for 24 weeks. Serum osteocalcin and urinary deoxypyridinoline (Dpd) levels were upregulated in rats in response to OVX, together with a significantly decreased BMD and trabecular bone area. The Pro, Fcs and Needling treatment improved the decreased BMD and the trabecular area, increased the trabecular number, lowered the trabecular separation to some extent as well as significantly depressed the urinary Dpd levels ( p < 0.05). The bone formation markers, such as the mineralizing surface, mineral apposition rate and bone formation rate were not significantly changed, along with a slightly higher trend of osteocalcin levels when compared with the Model rats. The slower heart rate and lower plasma NE levels in these therapeutic groups were also found. Our results suggested that propranolol, Fcs and needling on Sanyinjiao (SP-6) and Neiguan (PC-6) may improve the bone mass of OVX rats, and it provides an alternative and potential therapy for the prevention of postmenopausal osteoporosis.


Author(s):  
Edwige Nana Tchoupang ◽  
Sylvin Benjamin Ateba ◽  
Marie Alfrede Mvondo ◽  
Derek Tantoh Ndinteh ◽  
Télesphore Benoit Nguelefack ◽  
...  

Abstract Objectives There is a growing body of evidence indicating the potential of culinary herbs and spices to decrease the incidence of several chronic diseases or conditions. Because of this, the WHO recommends their regular consumption. In the Cameroonian culinary practices, “Nkui” is a famous dish made from a mixture of 10 spices. In our previous study, the ethanolic extract of this mixture exhibited promising estrogenic properties. Thus, this study aimed to evaluate its protective effects on some menopause-related cardiovascular and bone disorders. Methods For this purpose, a post-menopause-like model (ovariectomized rats) has been used. Animals were orally treated with the “Nkui” extract for 60 days. The investigation focused on the oxidative stress status, endothelial function (NO bioavailability), lipid profile, and bone mass, biochemical (calcium and inorganic phosphorus contents, serum alkaline phosphatase activity) and histomorphological features. Results The extract regulated lipid metabolism in a way to prevent accumulation of abdominal fat, gain in body weight and increased atherogenic indexes induced by ovariectomy. It prevented menopause-related low levels of nitric oxide and oxidative stress damage by increasing superoxide dismutase and catalase activities, while reducing glutathione and malondialdehyde levels in the heart and aorta. Moreover, it prevented ovariectomy-induced bone mass loss, bone marrow disparities and the disorganization of the trabecular network. It also increased femur calcium and inorganic phosphorus contents. Conclusions These results suggest that a regular consumption of “Nkui” may have health benefits on cardiovascular system and osteoporosis, major health issues associated with menopause.


Author(s):  
Akinleye Stephen Akinrinde ◽  
Halimot Olawalarami Hameed

Abstract Objectives This study examined the possible protective roles of exogenous glycine (Gly) and L-Arginine (l-Arg) against Diclofenac (DIC)-induced gastro-duodenal damage in rats. Methods Rats were divided into Group A (control), Group B (DIC group) and Groups C–F which were pre-treated for five days with Gly1 (250 mg/kg), Gly2 (500 mg/kg), l-Arg1 (200 mg/kg) and l-Arg2 (400 mg/kg), respectively, before co-treatment with DIC for another three days. Hematological, biochemical and histopathological analyses were then carried out. Results DIC produced significant (p<0.05) reduction in PCV (13.82%), Hb (46.58%), RBC (30.53%), serum total protein (32.72%), albumin (28.44%) and globulin (38.01%) along with significant (p<0.05) elevation of serum MPO activity (83.30%), when compared with control. In addition, DIC increased gastric H2O2 and MDA levels by 33.93 and 48.59%, respectively, while the duodenal levels of the same parameters increased by 19.43 and 85.56%, respectively. Moreover, SOD, GPx and GST activities in the DIC group were significantly (p<0.05) reduced in the stomach (21.12, 24.35 and 51.28%, respectively) and duodenum (30.59, 16.35 and 37.90%, respectively), compared to control. Treatment with Gly and l-Arg resulted in significant amelioration of the DIC-induced alterations although l-Arg produced better amelioration of RBC (29.78%), total protein (10.12%), albumin (9.93%) and MPO (65.01%), compared to the DIC group. The protective effects of both amino acids against oxidative stress parameters and histological lesions were largely similar. Conclusions The data from this study suggest that Gly or l-Arg prevented DIC-induced gastro-duodenal toxicity and might, therefore be useful in improving the therapeutic index of DIC.


Coatings ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Reham Z. Hamza ◽  
Mohammad S. Al-Harbi ◽  
Munirah A. Al-Hazaa

Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.


2018 ◽  
Vol 48 (6) ◽  
pp. 456-464 ◽  
Author(s):  
Jin Sug Kim ◽  
Kyung Sook Cho ◽  
Seon Hwa Park ◽  
Sang Ho Lee ◽  
Ji Hwan Lee ◽  
...  

Background: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis. Methods: Peritoneal fibrosis was induced by intraperitoneal (IP) injection of 0.1% chlorhexidine gluconate (CG) solution every other day for 4 weeks, with or without itraconazole treatment (20 mg/kg, IP injection on a daily basis). Male C57BL/6 mice were divided into 4 groups: saline group, saline plus itraconazole group, CG group, and CG plus itraconazole group. Isotonic saline was administered intraperitoneally to the control group. The peritoneal tissues were evaluated for histological changes, expression of fibrosis markers, and the main components of the SHH signaling pathway. Results: Peritoneal thickening was evident in the CG group and was significantly decreased by itraconazole administration (80.4 ± 7.7 vs. 28.2 ± 3.8 µm, p < 0.001). The expression of the following SHH signaling pathway components was upregulated in the CG group and suppressed by itraconazole treatment: SHH, patched, smoothened, and glioma-associated oncogene transcription factor 1. The IP injection of CG solution increased the expression of fibrosis markers such as α-smooth muscle actin and transforming growth factor-β1 in the peritoneal tissues. Itraconazole treatment significantly decreased the expression of these markers. Conclusion: Our study provides the first evidence that the SHH signaling pathway may be implicated in peritoneal fibrosis. It also demonstrates that itraconazole treatment has protective effects on peritoneal fibrosis through the regulation of the SHH signaling pathway. These findings suggest that blockage of the SHH signaling pathway is a potential therapeutic strategy for peritoneal fibrosis.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250885
Author(s):  
Zhaofang Chen ◽  
Kexin Shi ◽  
Wenjie Kuang ◽  
Lei Huang

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wang Gong ◽  
Xingren Chen ◽  
Tianshu Shi ◽  
Xiaoyan Shao ◽  
Xueying An ◽  
...  

As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis. The ovariectomized (OVX) mice were treated with normal saline or ZG for 4 weeks after ovariectomy following a series of analyses. The bone mass density (BMD) and trabecular parameters were examined by micro-CT. Bone remodeling was evaluated by the bone histomorphometry analysis and ELISA assay of bone turnover biomarkers in serum. The possible drug–disease common targets were analyzed by network pharmacology. To predict the potential biological processes and related pathways, GO/KEGG enrichment analysis was performed. The effects of ZG on the differentiation phenotype of osteoclasts and osteoblasts and the predicted pathway were verified in vitro. The results showed that ZG significantly improved the bone mass and micro-trabecular architecture in OVX mice compared with untreated OVX mice. ZG could promote bone formation and inhibit bone resorption to ameliorate ovariectomy-induced osteoporosis as evidenced by increased number of osteoblast (N.Ob/Tb.Pm) and decreased number of osteoclast (N.Oc/Tb.Pm) in treated group compared with untreated OVX mice. After identifying potential drug–disease common targets by network pharmacology, GO enrichment analysis predicted that ZG might affect various biological processes including osteoblastic differentiation and osteoclast differentiation. The KEGG enrichment analysis suggested that PI3K/Akt and mTOR signaling pathways could be the possible pathways. Furthermore, the experiments in vitro validated our findings. ZG significantly down-regulated the expression of osteoclast differentiation markers, reduced osteoclastic resorption, and inhibited the phosphorylation of PI3K/Akt, while ZG obviously up-regulated the expression of osteogenic biomarkers, promoted the formation of calcium nodules, and hampered the phosphorylation of 70S6K1/mTOR, which can be reversed by the corresponding pathway activator. Thus, our study suggested that ZG could inhibit the PI3K/Akt signaling pathway to reduce osteoclastic bone resorption as well as hamper the mTORC1/S6K1 signaling pathway to promote osteoblastic bone formation.


2021 ◽  
Vol 68 (1) ◽  
pp. 222-228
Author(s):  
Ahmet Özkaya ◽  
Kenan Türkan

In this study, the effects of 3-benzoyl-7-hydroxy coumarin molecule on mineral and antioxidant enzymes were investigated in rat liver exposed to oxidative stress with aluminium chloride (AlCl3). Adult male Wistar albino rats were divided into four groups as Control, Coumarin, AlCl3, and Coumarin + AlCl3. Coumarin at the dose of 10 mg/kg and AlCl3 at the dose of 8.3 mg/kg were administered for 30 days every other day. In AlCl3 group, malondialdehyde (MDA), iron (Fe), aluminium (Al) and copper (Cu) levels increased compared to the control group, while glutathione (GSH) level, glutathione S-transferase (GST), and carboxylesterase (Ces) enzyme activity levels decreased. In Coumarin + AlCl3 group, MDA, Fe, Al and Cu levels decreased with the effect of coumarin compared to AlCl3 group, while GSH level, and GST enzyme activity levels increased. According to our results, AlCl3 generates oxidative stress in rat livers, and we believe that 3-benzoyl-7-hydroxy coumarin has an ameliorative effect on antioxidant enzyme system, Al, Fe and Cu levels.


2021 ◽  
Vol 12 (2) ◽  
pp. 1762-1777

Doxorubicin (DOX) is effective chemotherapy in several malignancies, but large-scale toxicities limit its clinical usefulness. Propolis has been reported to exhibit a broad spectrum of biological activities. We aim to assess the protective efficacy of propolis against DOX-induced multi-toxicity in female rats. Forty female rats were divided into four groups: control group; Group (P) were administrated oral propolis (100 mg/kg once daily for 28 days); Group (P+DOX) were injected with a single intraperitoneal dose of DOX (20 mg/kg i.p at 24th day after the propolis administration) and group (DOX) were injected with doxorubicin only. Estimation of cardiac, renal and hepatic injury markers, apoptosis and pro-inflammatory cytokines were done using sera. Also, liver and heart tissue samples were collected to determine GSH and MDA as oxidative stress markers. In addition to histopathological and immunohistochemical examination of Cytochrome-C and Connexin43 on lysed myocardium, liver, kidney and lung tissues. Doxorubicin toxicity caused marked deteriorations of measured parameters through the different mechanisms in different body organs. However, pre-treatment with propolis significantly ameliorated these alterations. Thus propolis can ameliorate the DOX-induced experimental multi-toxicity as cardiomyopathy, hepatotoxicity, nephritis and pneumonia. Thus, it could be a promising protective agent in DOX treatment protocols.


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