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Li X, Yang J, Liang C, Yang W, Zhu Q, Luo H, Liu X, Wang J, Zhang J. Potential Protective Effect of Riboflavin Against Pathological Changes in the Main Organs of Male Mice Induced by Fluoride Exposure. Biol Trace Elem Res 2022; 200:1262-1273. [PMID: 33961201 DOI: 10.1007/s12011-021-02746-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 04/28/2021] [Indexed: 12/13/2022]
Abstract
Long-term exposure to excessive fluorine could cause damage to various tissues and organs in human and animals. However, there is no effective antidote to prevent and cure fluorosis except for avoiding fluoride intake. As an essential nutrient, riboflavin (VB2) has been identified to relieve oxidative stress and inflammation in animal tissues caused by other toxic substances, whether it can alleviate the damage caused by fluoride is unknown. For this, 32 ICR male mice were allocated to four groups of eight each. They were treated with 0 (distilled water), 100 mg/L sodium fluoride (NaF), 40 mg/L VB2, and their combination (100 mg/L NaF plus 40 mg/L VB2) via the drinking water for 90 consecutive days, respectively. The content of bone fluoride and the histomorphology of the main organs including liver, kidney, cerebral cortex, epididymis, small intestine, and colon were evaluated and pathologically scored. The results found that fluoride caused the pathological changes in liver, kidney, cerebral cortex, epididymis, small intestine, and colon at varying degrees, while riboflavin supplementation reduced significantly the accumulation of fluoride in bone, alleviated the morphological damage to cerebral cortex, epididymis, ileum, and colon. This study provides new clues for deeply exploring the mechanism of riboflavin intervention in fluorosis.
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Affiliation(s)
- Xiang Li
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Jie Yang
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Chen Liang
- College of Animal Science, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Wei Yang
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Qianlong Zhu
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Huifeng Luo
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Xueyan Liu
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Jundong Wang
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China
| | - Jianhai Zhang
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People's Republic of China.
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Dairy products and the French paradox: Could alkaline phosphatases play a role? Med Hypotheses 2016; 92:7-11. [DOI: 10.1016/j.mehy.2016.04.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 04/17/2016] [Indexed: 12/13/2022]
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Lewczuk B, Przybylska-Gornowicz B, Gajęcka M, Targońska K, Ziółkowska N, Prusik M, Gajęcki M. Histological structure of duodenum in gilts receiving low doses of zearalenone and deoxynivalenol in feed. ACTA ACUST UNITED AC 2015; 68:157-66. [PMID: 26679981 DOI: 10.1016/j.etp.2015.11.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2015] [Revised: 09/27/2015] [Accepted: 11/26/2015] [Indexed: 10/22/2022]
Abstract
Deoxynivalenol (DON) and zearalenone (ZEN), produced by microfungi of the Fusarium family, are among the most commonly occurring mycotoxins. They are considered important factors affecting human and animal health as well as livestock productivity. The aim of this study was to determine the effect of low doses of these mycotoxins on the histological structure of the pig duodenum. The study was performed on 72 gilts, with initial weights of approximately 25kg, divided into 4 equal groups. Group I received per os ZEN (40μg/kg BW), group II-DON (12μg/kg BW), group III-ZEN (40μg/kg BW) and DON (12μg/kg BW), and group IV-vehicle. The pigs were killed after 1, 2, 3, 4, 5 and 6 weeks of the treatment, and the duodenum samples were prepared for histological investigations. The slides were digitalized and subjected to morphometrical analysis. The treatment with DON and ZEN did not change the architecture of the mucosa or the ratio between goblet and adsorptive cells in the epithelium. The administration of DON induced an increase in the number of lymphocytes in the mucosal epithelium. Both mycotoxins, administered alone or together, increased the quantity of lymphocytes, plasma cells and macrophages with black-brown granules in the lamina propria. The time-courses of changes in the number of defense system cells evoked by DON and ZEN were different. In conclusion, dietary exposure to low doses of Fusarium mycotoxins should be considered an important risk factor for subclinical inflammation in the small intestine.
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Affiliation(s)
- Bogdan Lewczuk
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland.
| | - Barbara Przybylska-Gornowicz
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland
| | - Magdalena Gajęcka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland
| | - Krystyna Targońska
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland
| | - Natalia Ziółkowska
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland
| | - Magdalena Prusik
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland
| | - Maciej Gajęcki
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Poland
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Przybylska-Gornowicz B, Tarasiuk M, Lewczuk B, Prusik M, Ziółkowska N, Zielonka Ł, Gajęcki M, Gajęcka M. The effects of low doses of two Fusarium toxins, zearalenone and deoxynivalenol, on the pig jejunum. A light and electron microscopic study. Toxins (Basel) 2015; 7:4684-705. [PMID: 26569306 PMCID: PMC4663528 DOI: 10.3390/toxins7114684] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 10/05/2015] [Accepted: 11/03/2015] [Indexed: 11/16/2022] Open
Abstract
Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON.
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Affiliation(s)
- Barbara Przybylska-Gornowicz
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
| | - Michał Tarasiuk
- BIOMIN Polska Sp. z o.o., Grochowska 16, 04-217 Warszawa, Poland.
| | - Bogdan Lewczuk
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
| | - Magdalena Prusik
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
| | - Natalia Ziółkowska
- Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
| | - Łukasz Zielonka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
| | - Maciej Gajęcki
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
| | - Magdalena Gajęcka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
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Farooq SM, Boppana NB, Asokan D, Sekaran SD, Shankar EM, Li C, Gopal K, Bakar SA, Karthik HS, Ebrahim AS. C-phycocyanin confers protection against oxalate-mediated oxidative stress and mitochondrial dysfunctions in MDCK cells. PLoS One 2014; 9:e93056. [PMID: 24691130 PMCID: PMC3972226 DOI: 10.1371/journal.pone.0093056] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 03/02/2014] [Indexed: 12/04/2022] Open
Abstract
Oxalate toxicity is mediated through generation of reactive oxygen species (ROS) via a process that is partly dependent on mitochondrial dysfunction. Here, we investigated whether C-phycocyanin (CP) could protect against oxidative stress-mediated intracellular damage triggered by oxalate in MDCK cells. DCFDA, a fluorescence-based probe and hexanoyl-lysine adduct (HEL), an oxidative stress marker were used to investigate the effect of CP on oxalate-induced ROS production and membrane lipid peroxidation (LPO). The role of CP against oxalate-induced oxidative stress was studied by the evaluation of mitochondrial membrane potential by JC1 fluorescein staining, quantification of ATP synthesis and stress-induced MAP kinases (JNK/SAPK and ERK1/2). Our results revealed that oxalate-induced cells show markedly increased ROS levels and HEL protein expression that were significantly decreased following pre-treatment with CP. Further, JC1 staining showed that CP pre-treatment conferred significant protection from mitochondrial membrane permeability and increased ATP production in CP-treated cells than oxalate-alone-treated cells. In addition, CP treated cells significantly decreased the expression of phosphorylated JNK/SAPK and ERK1/2 as compared to oxalate-alone-treated cells. We concluded that CP could be used as a potential free radical-scavenging therapeutic strategy against oxidative stress-associated diseases including urolithiasis.
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Affiliation(s)
- Shukkur M. Farooq
- Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, United States of America
| | - Nithin B. Boppana
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, United States of America
| | - Devarajan Asokan
- Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Shamala D. Sekaran
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Esaki M. Shankar
- Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Chunying Li
- Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, Michigan, United States of America
| | - Kaliappan Gopal
- Department of Orthopedics, National Orthopedics Center for Excellence in Research and Learning (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sazaly A. Bakar
- Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Harve S. Karthik
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Abdul S. Ebrahim
- Department of Internal Medicine, Wayne State University, Detroit, Michigan, United States of America
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Methyl donor deficiency affects small-intestinal differentiation and barrier function in rats. Br J Nutr 2012; 109:667-77. [DOI: 10.1017/s0007114512001869] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Dietary methyl donors and their genetic determinants are associated with Crohn's disease risk. We investigated whether a methyl-deficient diet (MDD) may affect development and functions of the small intestine in rat pups from dams subjected to the MDD during gestation and lactation. At 1 month before pregnancy, adult females were fed with either a standard food or a diet without vitamin B12, folate and choline. A global wall hypotrophy was observed in the distal small bowel (MDD animals 0·30 mm v. controls 0·58 mm; P< 0·001) with increased crypt apoptosis (3·37 v. 0·4 %; P< 0·001), loss of enterocyte differentiation in the villus and a reduction in intestinal alkaline phosphatase production. Cleaved caspase-3 immunostaining (MDD animals 3·37 % v. controls 0·4 %, P< 0·001) and the Apostain labelling index showed increased crypt apoptosis (3·5 v. 1·4 %; P= 0·018). Decreased proliferation was observed in crypts of the proximal small bowel with a reduced number of minichromosome maintenance 6 (MDD animals 52·83 % v. controls 83·17 %; P= 0·048) and proliferating cell nuclear antigen-positive cells (46·25 v. 59 %; P= 0·05). This lack of enterocyte differentiation in the distal small bowel was associated with an impaired expression of β-catenin and a decreased β-catenin–E-cadherin interaction. The MDD affected the intestinal barrier in the proximal small bowel by decreasing Paneth cell number after immunostaining for lysosyme (MDD animals 8·66 % v. controls 21·66 %) and by reducing goblet cell number and mucus production after immunostaining for mucin-2 (crypts 8·66 v. 15·33 %; villus 7 v. 17 %). The MDD has dual effects on the small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats.
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Chen M, Peyrin-Biroulet L, George A, Coste F, Bressenot A, Bossenmeyer-Pourie C, Alberto JM, Xia B, Namour B, Guéant JL. Methyl deficient diet aggravates experimental colitis in rats. J Cell Mol Med 2012; 15:2486-97. [PMID: 21199330 PMCID: PMC3822959 DOI: 10.1111/j.1582-4934.2010.01252.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n= 12–16 per group): C DSS− (control/DSS−), D DSS− (deficient/DSS−), C DSS+ (control/DSS+) and D DSS+ (deficient/DSS+). Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied within colonic mucosa. In rat pups, the MDD produced a decreased plasma concentration of vitamin B12 and folate and an increased homocysteine (7.8 ± 0.9 versus 22.6 ± 1.2 μmol/l, P < 0.001). The DSS-induced colitis was dramatically more severe in the D DSS+ group compared with each other group, with no change in superoxide dismutase and glutathione peroxidase activity, but decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA levels of tumour necrosis factor (TNF)-α and protein levels of p38, cytosolic phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS+ pups and were accompanied by a decrease in the protein level of tissue inhibitor of metalloproteinases (TIMP)3, a negative regulator of TNF-α. MDD may cause an overexpression of pro-inflammatory pathways, indicating an aggravating effect of folate and/or vitamin B12 deficiency in experimental IBD. These findings suggest paying attention to vitamin B12 and folate deficits, frequently reported in IBD patients.
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Affiliation(s)
- Min Chen
- Inserm U954, Medical faculty and CHU of Nancy, Nancy-Université, Nancy, France
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Bodiga VL, Bodiga S, Surampudi S, Boindala S, Putcha U, Nagalla B, Subramaniam K, Manchala R. Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats. Nutrition 2011; 28:572-80. [PMID: 22189195 DOI: 10.1016/j.nut.2011.09.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2011] [Revised: 08/17/2011] [Accepted: 09/07/2011] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Chemotherapeutic agents induce small intestinal mucositis that is characterized structurally by crypt loss and villus atrophy and functionally by absorptive and barrier impairments. We studied the effect of selected individual vitamins and multiple-vitamin mixture supplementation in modulating cisplatin-induced intestinal damage and apoptosis. METHODS Thirty-six male Wistar/NIN rats 20 wk old and fed the control diet (AIN-93G) were randomly divided into six groups. Five groups were administered cisplatin (2.61 mg/kg of body weight) once a week for 3 wk and were concomitantly provided the control diet or riboflavin, folate, α- tocopherol, or a multiple-vitamin mixture supplemented diet. The sixth group served as a control for cisplatin and received saline as the vehicle. Intestinal epithelial cell apoptosis was monitored by morphometry, M30 staining, DNA fragmentation, and caspase-3 activity. Functional and structural integrities were determined by measuring activities of alkaline phosphatase and lysine ala-dipeptidyl aminopeptidase and the villus height/crypt depth ratio. Oxidative burden was assessed as the formation of thiobarbituric acid-reactive substances and protein carbonyls. Plasma levels of selected vitamins were also measured. RESULTS Cisplatin administration significantly increased intestinal apoptosis in the villus and crypt regions that correlated with increased oxidative damage, decreased Bcl-2/Bax, and compromised functional integrity. Riboflavin, folate, and the multiple-vitamin mixture supplementation attenuated the cisplatin-induced increase in apoptotic indices, with a decrease in oxidative burden, increased Bcl-2/Bax, and improved functional and structural integrities. The α-tocopherol supplementation, although effective in attenuating oxidative stress and improving functional integrity, failed to lower the apoptotic indices. CONCLUSIONS Riboflavin, folate, and the multiple-vitamin supplementation proved to be more efficacious in attenuating the cisplatin-induced intestinal damage and associated changes in apoptosis.
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Affiliation(s)
- Vijaya Lakshmi Bodiga
- Pathology Division, National Institute of Nutrition, Hyderabad, Andhra Pradesh, India.
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Jiang Y, Du HZ, Zhu WY, Xiao HJ, Huang CY. Effects of a regional Chinese diet and its vitamin supplementation on proliferation of human esophageal cancer cell lines. BIOMEDICAL AND ENVIRONMENTAL SCIENCES : BES 2008; 21:442-448. [PMID: 19133620 DOI: 10.1016/s0895-3988(08)60067-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
OBJECTIVE To study the effects of a local diet popular in Yanting region (YT diet) on the proliferation of two human cell lines (Eca-109 esophageal squamous cell carcinoma line and HL7702 normal liver epithelial cell line) in rats by a sero-physiological approach. METHODS Male SD rats were divided into six groups and fed respectively with a conventional diet and the YT diet (one of the five experimental diets) supplemented with two vitamin mixtures (Mix. 1: vitamins A, E, and folic acid; Mix.2: mix.1 plus riboflavin and vitamin C) at two different doses. On the 30th day, sera were collected from the rats and added into a medium for cell culture, with 10% FBS used as a serum control. The effects were assessed by MTT assay, DNA synthesis and flow cytometry assays. RESULTS Compared with the control, the sera from rats fed with the YT diet significantly promoted the proliferation of Eca-109 cells, which was, however, reversed by the supplementation with two vitamin mixtures at high doses. Surprisingly, the same treatment produced contrary effects on HL7702 cells as compared with Eca-109 cells. CONCLUSION The sera from rats fed with the YT diet could promote the proliferation of human esophageal cancer cell line Eca-109, whereas the sera from those fed with the YT diet supplemented with vitamin mixtures might have inhibitory effects on the proliferation of Eca-109 cells.
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Affiliation(s)
- Yan Jiang
- Department of Nutrition and Food Hygiene, West China School of Public Health, Sichuan University, Chengdu 610041, Sichuan, China
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Choi KM, Yoon HH, Seo YK, Song KY, Kwon SY, Lee HS, Park YS, Kim YJ, Park JK. Effect of essential and nonessential amino acid compositions on the in vitro behavior of human mesenchymal stem cells. KOREAN J CHEM ENG 2008. [DOI: 10.1007/s11814-007-0121-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Vijayalakshmi B, Sesikeran B, Udaykumar P, Kalyanasundaram S, Raghunath M. Chronic low vitamin intake potentiates cisplatin-induced intestinal epithelial cell apoptosis in WNIN rats. World J Gastroenterol 2006; 12:1078-85. [PMID: 16534849 PMCID: PMC4087900 DOI: 10.3748/wjg.v12.i7.1078] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate if cisplatin alters vitamin status and if VR modulates cisplatin induced intestinal apoptosis and oxidative stress in Wistar/NIN (WNIN) male rats.
METHODS: Weanling, WNIN male rats (n = 12 per group) received adlibitum for 17 wk: control diet (20% protein) or the same with 50% vitamin restriction. They were then sub-divided into two groups of six rats each and administered cisplatin (2.61 mg/kg bodyweight) once a week for three wk or PBS (vehicle control). Intestinal epithelial cell (IEC) apoptosis was monitored by morphometry, Annexin-V binding, M30 cytodeath assay and DNA fragmentation. Structural and functional integrity of the villus were assessed by villus height / crypt depth ratio and activities of alkaline phosphatase, lys, ala-dipeptidyl amino-peptidase, respectively. To assess the probable mechanism(s) of altered apoptosis, oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined.
RESULTS: Cisplatin per se decreased plasma vitamin levels and they were the lowest in VR animals treated with cisplatin. As expected VR increased only villus apoptosis, whereas cisplatin increased stem cell apoptosis in the crypt. However, cisplatin treatment of VR rats increased apoptosis both in villus and crypt regions and was associated with higher levels of TBARS, protein carbonyls and caspase-3 activity, but lower GSH concentrations. VR induced decrease in Bcl-2 expression was further lowered by cisplatin. Bax expression, unaffected by VR was increased on cisplatin treatment. Mucosal functional integrity was severely compromised in cisplatin treated VR-rats.
CONCLUSION: Low intake of vitamins increases the sensitivity of rats to cisplatin and promotes intestinal epithelial cell apoptosis.
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Affiliation(s)
- Bodiga Vijayalakshmi
- Department of Pathology, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania, Hyderabad-500007, Andhra Pradesh, India
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