Frontiers in Neuroscience
·
2021
·
IF 4.677
Wang Rui,Hong Ming,Huang Jingyi,Zhou Na,Zhang Yao,Xu Siyuan,Liu Jiaye,Yuan Junjie,Zhang Lusiqi,Huang Linyuan,Huang Ping,Tan Bo,Cao Hong-ying
Aim: This research aimed to investigate the neurotoxicity of low-dose cyclophosphamide (CYP) on the urinary bladder of rats by in vivo and in vitro studies.Methods: To establish CYP-induced cystitis rat model, rats were treated with three intraperitoneal injections of CYP (25 mg/kg) in a week. During treatment, the up-down method was used to assess the mechanical withdrawal threshold. On day 8, urodynamic test and bladder smooth muscle contractility study, including the contraction of bladder strips to electrical field stimulation (EFS, 2–64 Hz), carbachol (CCh, 10–8–10–5 M) and KCl (120 mM), were performed to evaluate the function of bladder function. Body weight and bladder weight were also recorded. Morphometric analysis using an optical microscope and transmission electron microscope was performed to observe the changes of microstructure and submicrostructure of the bladder. The major pelvic neurons were isolated and treated with acrolein (the main CYP metabolite) to assess apoptosis in vitro. RT-PCR assays were used to quantify the mRNA expression levels of Nlrp6, Asc, Casp11 and Casp1 in bladder tissues and primary neurons.Results: After CYP injections, the body weights decreased, but the bladder weights increased in the model group. The mechanical withdrawal threshold of the cystitis model remained at a low level. The morphometric analysis suggested bladder inflammation and neuroinflammation in the bladder of the cystitis rat model. Urodynamic test revealed that, the amplitude, the pressure baseline, the peak pressure and pressure threshold of model rats significantly increased after CYP treatment. The muscle strips of model rats exhibited significantly higher contractility caused by EFS and CCh than the controls. Apoptotic cells appeared at the highest concentration group (100 μM acrolein) after 6 h of acrolein incubation in apoptosis assay of primary neurons. The mRNA expression levels of Nlrp6 and Casp11 were significantly increased in the cystitis rat model and in the acrolein-treated neurons.Conclusions: Low-dose CYP treatment was confirmed to induce nerve injury, which leading to bladder pain and overactive bladder in female rats, and the up-regulation of Nlrp6 and Casp11 may contribute to these pathological changes.
研究领域:
药理学
·
神经科学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
Antioxidants
·
2020
·Vol. 9
·期 8
·745
·
IF 5.014
Shuoqi Jiang,Zhuangwei Zhang,FangFang Huang,Zuisu Yang,Fangmiao Yu,Yunping Tang,Guofang Ding
The major component of theSolenocera crassicornishead protein hydrolysates-fraction 1 (SCHPs-F1) are low molecular weight peptides (MW < 1 kDa). In this study, we investigated the potential renoprotective effects of SCHPs-F1 in a cyclophosphamide (CTX) toxicity mouse model. In brief, 40 male mice were randomly divided into 5 groups and received either saline or 80 mg/kg body weight (BW) CTX by intraperitoneal injection for 5 days, followed by either saline or SCHPs-F1 (100, 200, and 400 mg/kg BW) by intragastric administration for 15 days. SCHPs-F1 treatment significantly reversed the CTX-induced decreases in the levels of blood urea nitrogen (BUN), creatinine (CRE), and cytochrome P450 (CYP450), as well as the renal histological lesions. Furthermore, the results indicated that SCHPs-F1 potentially alleviated CTX-induced nephrotoxicity through mitigating inflammatory responses, oxidative stress, and apoptosis status of the kidneys, as evidenced by decreased levels of malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ and increased levels of total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, overexpression of pro-apoptotic proteins pair B-cell lymphoma-2 (Bcl-2)-associated X (Bax)/Bcl-2, cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 in renal tissues were suppressed by treatment with SCHPs-F1. In addition, the protein levels of the antioxidant factor nuclear factor erythroid-2 related factor 2 (Nrf2) and the expression levels of its downstream target genes heme-oxygenase (HO-1), glutamate-cysteine ligase modifier subunit (GCLM) and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were stimulated by treatment with SCHPs-F1 in the CTX-induced renal injury model. Taken together, our data suggested that SCHPs-F1 could provide a novel potential strategy in mitigating the nephrotoxicity caused by CTX.Keywords:apoptosis;cyclophosphamide;inflammation;oxidative stress;peptides;Solenocera crassicornis
研究领域:
药理学
·
毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2025
·
IF 2.8
Cong Feng,Yue Jiang,Yi Wang,Yuehui Zhang,Yu Liu,Jia Li
Premature ovarian insufficiency (POI) is a prevalent gynecological disorder. Cyclophosphamide (CP), as a chemotherapeutic drug, particularly plays an important role in inducing POI. Protocatechualdehyde (PCA) is a major phenolic acid in Chinese herb Danshen, and has been reported to have beneficial effects on anti-inflammatory, anti-apoptotic, and anti-oxidant functions. We aimed to investigate the effect of different doses of PCA on ovarian function and the underlying molecular mechanisms. PCA administration reduced estrous cycle disorders, increased ovarian weight, promoted the secretion of serum hormone levels, and improved the CP-damaged ovarian microenvironment. Importantly, the administration of PCA contributed to the recovery of ovarian function with POI by inhibiting the senescence and apoptosis of granulosa cells. In vitro assay further confirmed the protective effect of PCA on CP-induced senescence and apoptosis of granulosa cells. Mechanistically, both in vivo and in vitro experiments proved that PCA administration promoted activation of the Sirt1/p53 signaling cascade, ultimately improving ovarian function. In conclusion, PCA might protect against ovarian damage in CP-induced POI that might be related to its activity on senescence and apoptosis of granulosa cells by the Sirt1/p53 pathway.
研究领域:
生殖医学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Zhiying Zhang,Ting Pan,Chunrong Liu,Xiaoyun Shan,Zeqiong Xu,Huachang Hong,Hongjun Lin,Jianrong Chen,Hongjie Sun
The widespread use of cyclophosphamide (CP) in medical treatment had caused ubiquitous contamination in the environment. To data, many studies have been carried out on the toxic effect of CP. However, among these toxic effects of CP, which are the most sensitive remains unclear. Present study aimed to investigate the toxicity of CP on mice and evaluate the sensitivity of physiological-biochemical parameters upon exposure of mice to CP. Results showed that as compared with the control group, CP caused significant reduction in body weight (p < 0.01), spleen coefficient (p < 0.01), leukocyte density (p < 0.01) and alanine transaminase (ALT) in kidney (p < 0.01); However superoxide dismutase (SOD), malondialdehyde (MDA), ALT in liver and creatinine (Cr) in kidney significantly (p < 0.05) increased. Among the suppressed physiological and biochemical parameters, the sensitivity to CP toxicity was generally ranked as body weight > leukocyte density > ALT in kidney > spleen coefficient; while among the stimulated parameters, the sensitivity was ranked as MDA (liver) > Cr (kidney) > ALT (liver). Overall, the most sensitive parameters to CP toxicity may be associated with growth, immune system and the normal function of liver and kidney.
研究领域:
毒理学
·
生物化学
·
环境科学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 12
·10297
·
IF 5.6
Rui Zhao,Shuoqi Jiang,Yunping Tang,Guofang Ding
This study aimed to investigate the immunoenhancement effects of low molecular weight peptides (SCHPs-F1) from red shrimp (Solenocera crassicornis) head against cyclophosphamide (CTX)-induced immunosuppressed mice. ICR mice were intraperitoneally injected with 80 mg/kg CTX for 5 consecutive days to establish the immunosuppressive model and then intragastrically administered with SCHPs-F1 (100 mg/kg, 200 mg/kg, and 400 mg/kg) to investigate its improving effect on immunosuppressed mice and explore its potential mechanism using Western blot. SCHPs-F1 could effectively improve the spleen and thymus index, promoting serum cytokines and immunoglobulins production and upregulating the proliferative activity of splenic lymphocytes and peritoneal macrophages of the CTX-treated mice. Moreover, SCHPs-F1 could significantly promote the expression levels of related proteins in the NF-κB and MAPK pathways in the spleen tissues. Overall, the results suggested that SCHPs-F1 could effectively ameliorate the immune deficiency caused by CTX and had the potential to explore as an immunomodulator in functional foods or dietary supplements.Keywords:low molecular weight peptides;immunoenhancement;cyclophosphamide;Solenocera crassicornis;signal pathways
研究领域:
免疫学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Yan Zhang,Hui Wang,Qin Ge,Jing Shi,Huiying Zhang,Jiaqi Gao,Jiaxin Han
MLS is a bioactive extract of Melientha longistaminea shoots. In this study, we characterized the preliminary structure of MLS. And establish in vivo immune model experiments. To investigate the potential mechanism of immunomodulatory effects on CTX-induced immunosuppressed mice. From the experimental results, we found that MLS restored immune organ damage in immunosuppressed mice, increased cytokine and immunoglobulin secretion in the spleen, and attenuated oxidative damage to the liver by CTX. Meanwhile, MLS was also effective in ameliorating immune injury in immunosuppressed mice by activating the NF-κB and Nrf2 signaling pathways. MLS effectively improved the composition of the gut flora and increased the production of SCFAs in the gut. The results indicate that MLS has immunomodulatory effects and provides a research basis for developing Melientha longistaminea polysaccharides as immunomodulatory adjuvants.
研究领域:
免疫学
·
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 8
·期 9
·3383-3393
·
IF 3.247
Hongjie Shi,Yaoguang Chang,Yuan Gao,Xiong Wang,Xin Chen,Yuming Wang,Changhu Xue,Qingjuan Tang
Cyclophosphamide (cy) is a widely used cancer drug. Many researchers have focused on the prevention and alleviation of its side effects, particularly damage to the intestinal mucosal barrier. In this study, we examined the effects of fucoidan, isolated from Acaudina molpadioides, on mice with intestinal mucosal damage induced by cyclophosphamide. Our results showed that fucoidan intervention could relieve injury such as decreasing inflammation and increasing the expression of tight junction proteins, and 50 kDa fucoidan significantly increased the abundance of short chain fatty acid (SCFA) producer Coprococcus, Rikenella, and Butyricicoccus (p < 0.05, p < 0.001, and p < 0.05, respectively) species within the intestinal mucosa compared with the cyclophosphamide group, as determined by 16S rDNA gene high-throughput sequencing. In addition, SCFAs, particularly propionate, butyrate, and total SCFAs, were increased in the feces, and SCFA receptors were upregulated in the small intestine. The protective effects of fucoidan on cyclophosphamide treatment may be associated with gut microflora, and 50 kDa fucoidan had superior effects. Therefore, fucoidan may have applications as an effective supplement to protect against intestinal mucosal barrier damage during chemotherapy.
研究领域:
药理学
·
微生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 5
·4291-4303
·
IF 4.171
Wenyan Huo,Zhengping Feng,Suying Hu,Langjun Cui,Ting Qiao,Lu Dai,Peng Qi,Liguang Zhang,Yu Liu,Junzhi Li
Polysaccharides isolated from mushrooms have been identified as potential prebiotics that could impact gut microbiota. In this study, a water-soluble polysaccharide (MP) extracted from wild morels was evaluated for its effects on the gut microbiota of non-treated and cyclophosphamide (CP)-treated mice. The results showed that MP restored the spleen weight and increased the counts of white blood cells and lymphocytes in the peripheral blood and spleen of the CP-treated mice. Mice treated with MP exhibited increased levels of short-chain fatty acid (SCFA)-producing bacteria, especially Lachnospiraceae, compared to normal mice, and increased levels of Bacteroidetes and SCFA-producing bacteria, especially Ruminococcaceae, compared to the CP-treated mice. Moreover, MP treatment increased the production of valeric acid and decreased the production of acetic acid in the non-treated mice and increased the production of acetic acid, propionic acid, butyric acid, and valeric acid in the CP-treated mice. These results show that MP is potentially good for health.
研究领域:
免疫学
·
微生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2021
·Vol. 57
·期 1
·92-100
·
IF 3.713
Wei Wang,Lijun Fan,Xuewen Li,Zirong Wang,Jianzhong Zhou,Buligen Jialengbieke,Jianye Ren,Xiaodong Hu
In this study, the digestion of pectic polysaccharide from Brassica rapa L. (BRP) in vitro and its effect on the intestinal microbiota in cyclophosphamide (Cy)-treated mice were investigated. As a result, the molecular weight ( M w ) of BRP was significantly decreased after simulated gastrointestinal digestion, and content of reducing sugars ( C R ) was significantly increased ( P < 0.05), implying that BRP was gradually degraded under gastrointestinal digestion conditions in vitro . In vivo , both 50 or 200 mg kg −1 ·BW/d of BRP significantly improved SCFAs concentrations that decreased by Cy treatment ( P < 0.05). Meanwhile, BRP enriched the alpha-diversity of intestinal microbiota and altered the microbial composition with an increase of Lactobacillus and a decrease of Clostridium, Ruminococcus, Oscillospira ( P < 0.05). Besides, BRP intervention was conducive to the recovery of mouse body weight, thymus and spleen indices, and contributed to improve the intestinal barrier.
研究领域:
食品科学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 9
·2754
·
IF 4.927
Lirong Guo,Qing Gao,Jieqiong Zhu,Xiaobao Jin,Hui Yin,Tao Liu
Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy.N-Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (Lepidium meyenii). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury.Keywords:docosahexaenoic acids;ovary;granulosa cells;cyclophosphamide;macamide
研究领域:
药理学
·
生殖生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND AGRICULTURAL IMMUNOLOGY
·
2016
·
IF 1.548
Wenlong Liu,Jian Chen,Qiang Li,Aidong Sun
To supply reference for further antitumor mechanism studies, the antitumor effect of acylated blueberry anthocyanin (ABA) was studied on H22 murine-transplanted tumor experiment. Mice treated with ABA in combination with cyclophosphamide (CTX) had 53.74% life extension rate. CTX also has significant antineoplastic effect, which could inhibit tumor growth by 63.12%. The spleen and thymus indices decreased by CTX also ameliorated considerably. The activities of alanine aminotransferase and aspartate aminotransferase were significantly lower compared with model group. Malondialdehyde, the product of lipid peroxidation was also decreased. Meanwhile, the activities of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase, were enhanced in a dose-dependent manner (P < .05). Electron microscopy images showed that tumor cells in the mix group had a large sheet of necrosis than the other groups. ABA had strong antitumor effect on H22, as well as synergetic and attenuated toxic effect when combined with CTX.
研究领域:
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Food Science & Nutrition
·
2024
·
IF 3.5
XinQian Rong,QingLong Shu
Astragalus polysaccharide is one of the most extensively studied traditional Chinese medicinal polysaccharides because of its immunomodulatory activity and has attracted considerable attention. Existing evidence suggests that its potential immunomodulatory mechanism is related to the modulation of intestinal microbiota. However, current research methods on the gut microbiota mainly focus on 16S rRNA sequencing, providing limited evidence of specific changes in functional bacterial groups in the intestine. Butyrate is a class of short-chain fatty acids among the microbial metabolites in the gut and is most closely associated with immunomodulatory activity. Thus, in this study, we extracted and purified a polysaccharide from astragalus composed of a main chain of →4)-α-D-Glcp-(1 → and →4,6)-α-D-Glcp-(1→, with side chains of →6)-α-D-Glcp-(1→ and aggregated arabinose, and investigated the changes in butyrate-producing bacterial groups in mice during the immunomodulation process of astragalus polysaccharide, using two butyrate-producing bacterial-specific primers. The results showed that oral administration of astragalus polysaccharide significantly increased butyrate production in the mouse intestine, restoring the disrupted butyrate-producing bacterial abundance and diversity caused by immunosuppression. In conclusion, our study provides the first evidence of the targeted modulation of the butyrate-producing gut microbiota by astragalus polysaccharide, offering insights into its pharmacological activity.
研究领域:
药理学
·
免疫学
·
微生物学
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）