scholarly journals Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7021
Author(s):  
Aishah E. Albalawi ◽  
Norah A. Althobaiti ◽  
Salma Saleh Alrdahe ◽  
Reem Hasaballah Alhasani ◽  
Fatima S. Alaryani ◽  
...  

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.

2016 ◽  
Vol 35 (8) ◽  
pp. 877-886 ◽  
Author(s):  
M Bacanlı ◽  
S Aydın ◽  
G Taner ◽  
HG Göktaş ◽  
T Şahin ◽  
...  

Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated rats was significantly lower than that in the sepsis-induced rats. RA treatment also decreased the MDA levels and increased the GSH levels and SOD and GSH-Px activities in the livers and kidneys of the sepsis-induced rats. Plasma TNF-α level was found to be decreased in the RA-treated rats. It seems that RA might have a role in the attenuation of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing the antioxidant status and DNA repair capacity of the animals.


2020 ◽  
Vol 10 (03) ◽  
pp. 319-322
Author(s):  
Ahmed Abdul-Hassan Abbas ◽  
Zainab J. Fadhil ◽  
Shatha Hussein Ali

Introduction: Cytokines act as a mediator of inflammation in childhood nephrotic syndrome. Polymorphisms of cytokines genes may influence susceptibility to nephrotic syndrome (NS), as well as, patients’ steroid responses. Objective: To study the association of tumor necrosis factor-alpha single nucleotide polymorphisms (TNF-α SNP) (-863 C/A) with the development of NS in addition to access to their effects on serum level of TNF and the response to steroid therapy. Patients and Methods: This study included 60 patients (19 female and 41 male) with nephrotic syndrome; their ages ranged from 2 to 18 years. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess the TNF-α gene polymorphism. Results: According to the digestion pattern of RFLP-PCR products of TNF-α-863, this polymorphism had three genotypes, which were CC, CA, and AA, in both NS patients and controls. Also, the current result observed that -863 SNP do not affect the serum level of TNF-α and steroid responsiveness in patients with nephrotic syndrome. Conclusion: This polymorphism did not show any significant association with response to steroid therapy and TNF serum level neither at genotype nor at allele level.


Author(s):  
Christofani Ekapatria

Objective: To analyze the difference of PlGF and TNF-α serum level between early-onset and late-onset preeclampsia. Method: This is a cross-sectional analytic comparative study comparing serum level of PlGF and TNF-α between groups with earlyand late-onset preeclampsia. Each group consists of 32 subjects who met inclusion criteria and presented to Dr. Hasan Sadikin Hospital or its district hospitals in September - November 2012. Statistical analysis was performed with Kolmogorov Smirnov test, Saphiro-Wilk test, and non-parametric Mann-Whitney test. Result: Mean of PlGF serum level in the group with early-onset preeclampsia is 53.0344±38.07140 pg/ml, while mean of which in the group with late-onset preeclampsia is 241.8063±192.8373 pg/ml (p


1998 ◽  
Vol 66 (12) ◽  
pp. 5792-5798 ◽  
Author(s):  
Keiji Funatogawa ◽  
Motohiro Matsuura ◽  
Masayasu Nakano ◽  
Makoto Kiso ◽  
Akira Hasegawa

ABSTRACT Lipid A is the active center of bacterial lipopolysaccharide (LPS), which exhibits diverse biological activities via the production of various mediators. We investigated the production of nitric oxide (NO), one of the mediators, by a murine macrophage cell line, RAW264.7, upon stimulation with a series of monosaccharide lipid A analogues to elucidate the relationship of structure and activity in NO production. The production of other representative mediators, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), was also investigated to compare the structural requirements for the production of these cytokines with those for the production of NO. Structure-activity relationships in NO production correlated well with those in the production of TNF-α and IL-6. Among the lipid A analogues possessing different numbers of acyl groups on a 4-O-phosphono-d-glucosamine backbone, compounds like GLA-60 that possess three tetradecanoyl (C14) groups exhibited stronger activities in the production of the mediators than compounds possessing four or two C14 groups. Time course study of the production of these mediators showed that production of NO started and peaked later than those of TNF-α and IL-6. Neither neutralization of TNF-α activity by antibody nor suppression of TNF-α production by pentoxifylline showed a significant suppressive effect on production of NO and IL-6 upon stimulation with LPS or lipid A analogues. Neutralization of IL-6 activity by antibody showed no significant suppressive effect on production of NO and TNF-α. A monosaccharide lipid A analogue (GLA-58) which exhibited no detectable agonistic activity showed a suppressive effect on the production of all three mediators upon stimulation with LPS or lipid A analogues. These results indicate that signals for NO production by LPS agonists in murine macrophages are transduced in good correlation with those for production of TNF-α and IL-6, although they are not transduced via production of those cytokines.


2002 ◽  
Vol 70 (8) ◽  
pp. 4092-4098 ◽  
Author(s):  
Kazuyoshi Kawahara ◽  
Hiroko Tsukano ◽  
Haruo Watanabe ◽  
Buko Lindner ◽  
Motohiro Matsuura

ABSTRACT Yersinia pestis strain Yreka was grown at 27 or 37°C, and the lipid A structures (lipid A-27°C and lipid A-37°C) of the respective lipopolysaccharides (LPS) were investigated by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Lipid A-27°C consisted of a mixture of tri-acyl, tetra-acyl, penta-acyl, and hexa-acyl lipid A's, of which tetra-acyl lipid A was most abundant. Lipid A-37°C consisted predominantly of tri- and tetra-acylated molecules, with only small amounts of penta-acyl lipid A; no hexa-acyl lipid A was detected. Furthermore, the amount of 4-amino-arabinose was substantially higher in lipid A-27°C than in lipid A-37°C. By use of mouse and human macrophage cell lines, the biological activities of the LPS and lipid A preparations were measured via their abilities to induce production of tumor necrosis factor alpha (TNF-α). In both cell lines the LPS and the lipid A from bacteria grown at 27°C were stronger inducers of TNF-α than those from bacteria grown at 37°C. However, the difference in activity was more prominent in human macrophage cells. These results suggest that in order to reduce the activation of human macrophages, it may be more advantageous for Y. pestis to produce less-acylated lipid A at 37°C.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Guan Min-chang ◽  
Tang Wei-hong ◽  
Xu Zhen ◽  
Sun Jie

The purpose of this study was to compare the effect and toxicity of organic selenium (Pro-Se) with inorganic selenium (IOSe) in preventing asthma in ovalbumin-induced asthmatic mice. After the mice were treated orally with Pro-Se and IOSe, respectively, the plasma Se levels, Se accumulation in liver and kidney, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), oxidative stress, and NF-κB activation in lung were examined. The results showed that the serumal Se levels in the mice fed the Pro-Se were significant (P<0.01) elevations. It results in restoration of the level of endogenous antioxidant enzyme, lower levels of TNF-αand IL-1β, and activated NF-κB in the asthmatic mice. Our experiments have demonstrated profound differences between the activities of organic selenium and inorganic selenium in experimental conditions. These data provide an important proof of the concept that organic selenium might be a new potential therapy for the management of childhood asthma in humans.


2019 ◽  
Vol 24 (3) ◽  
pp. 169
Author(s):  
Yuli Trisetiyono ◽  
Noor Pramono ◽  
Syarief Thaufik Hidayat ◽  
Widjiati Widjiati

The pathological pathway of endometriosis remains unclear and involves complex etiologies. Increased oxidative stress is understood to be related to this disease. Oxidative stress produces reactive oxygen species, causes inflammation that is characterized by recruiting lymphocytes and phagocyte activation, produces cytokines that induce oxidation enzyme, and supports epithelium growth. Oxidative stress conjointly will increase angiogenesis and promotes the proliferation of endometriosis tissue within the peritoneal cavity. Kebar grass and green tea contain high antioxidants, are expected to extend antioxidant defense leading to reduced oxidative stress, inflammation, angiogenesis, and reduced endometriosis tissue implants. The objective is to analyze the consequences of Kebar grass and green tea extract to MDA serum level, TNF-α, and VEGF expression, and the area of the endometriotic implants in the mice models.  The study was an experiment designed. It has been conducted within the Department of Obstetrics Gynecology, Faculty of Medicine Diponegoro University and Faculty of Veterinary Medicine Airlangga University. Twenty-one mice were divided into three groups, i.e., the first group of mouse models was given Kebar extract 3 mg/day; the second group was assigned green tea extract 1.1 mg/day; therefore the third group was a control group contains the untreated endometriosis mice. Each treatment was given for fourteen days. MDA serum level was measured by specto-photometric examination, the area of the endometriotic implants was measured by computer tracing technique, whereas TNF-α and VEGF expression of endometriotic implants were measured by IHC using Rammele Scale Index (ImmunoReactive Score). The MDA serum levels of the groups treated with Kebar grass extract and green tea extract were significantly lower than the control group (0.09±0.022 mmol, 0.07±0.019 mmol, and 0.30±0.062 mmol, respectively; p=0.001). TNF-α expression of the groups supplied with each treatment also lower than the control groups (2.43±1.521, 3.66±1.422, and 7.26±2.898, respectively; p=0.002). However, VEGF expression was not significantly different between Kebar grass extract group, green tea group, and the control (4.34±2.402, 4.57±1.998, 7.40±3.495, respectively; p=0.089). Finally, the area of the endometriotic implants of the mice models administered with all treatment was smaller than the control group (0.01±0.025 mm2, 8.76±18.776 mm2, and 34.80±13.079 mm2, respectively; p=0.003). Conclusion: Kebar grass extract, as well as green tea extract administration to endometriosis model mice, resulted in lower MDA serum level and TNF-α expression, smaller the area of endometriotic implants compared, but not resulted in a significant difference of VEGF expression.


2020 ◽  
Vol 10 (3) ◽  
pp. e21-e21
Author(s):  
Ali Valibeik ◽  
Negar Naderi ◽  
Abdolhakim Amini ◽  
Niloufar Tavakoli Dastjerd ◽  
Sobhan Rahimi Monfared ◽  
...  

Introduction: Camphor is a natural antioxidant with anti-inflammatory and tissue repair properties. Nephrotoxicity is the most important side effect of gentamicin (GEM) administration. Therefore, investigating the effect of natural antioxidants can resolve this complication. Objectives: We aimed to assay the effect of camphor on biochemical factors and gene expression of antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPX]) and inflammatory markers (tumor necrosis factor-alpha [TNF-α], nuclear factor kappa-B [NF-κB], interleukine-6 [IL-6]), and apoptotic indices (BCL2-associated X protein [Bax], B-cell lymphoma 2 [Bcl-2], caspase-3)], against GEM-induced nephrotoxicity in rats. Materials and Methods: Thirty adult male Wistar rats were allocated to five groups. Positive control and treatment groups were given GEM to induce nephrotoxicity. Animal treatment groups were treated with camphor in olive oil for 12 days. Renal biopsies, serum, extraction of renal tissue and urine of rats were taken after the twelfth day. Biopsies were examined for structural changes using a light microscope, moreover, apoptosis, desired biochemical and inflammatory factors, were investigated by suitable methods. Results: Camphor had no effect on biochemical factors, including malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), urea, creatinine and urine protein. However, it reduced the gene expression of TNF-α, NF-κB, IL-6, Bax, and caspase-3 and increased the gene expression of GPX and CAT and Bcl-2. Moreover, camphor improved kidney histopathological changes in the camphor groups in comparison with the GEM group. Conclusion: Camphor can be useful in the attenuation of GEM-induced nephrotoxicity based on expression levels of examined enzymes and factors and improving kidney histopathological changes.


Sign in / Sign up

Export Citation Format

Share Document