Effects of vitamin restriction and supplementation on rat intestinal epithelial cell apoptosis.
Diet influences intestinal growth and function and vitamins modulate intestinal cell turnover. We have assessed the effects of chronic, moderate (50% of control) vitamin restriction and supplementation on intestinal epithelial cell (IEC) apoptosis and the relevance of this to alterations in tissue oxidative stress and antioxidant status. Feeding a vitamin-restricted diet to male, weanling WNIN rats for 20 weeks significantly increased IEC apoptosis, but only in the villi region, as evident from increased annexin V staining, M30 positivity, histological observations, DNA ladder formation, and reduced expression of Bcl-2. This was associated with elevated levels of lipid peroxides and protein carbonyls in the intestinal mucosa despite the increased activities of superoxide dismutase, catalase, and glutathione peroxidase. Consistent with the increased oxidative stress and apoptosis, structural and functional integrity of the villi were compromised as evident from the lowered ratio of villus height:crypt depth and the decreased activities of the membrane marker enzymes alkaline phosphatase and Lys-Ala dipeptidyl aminopeptidase. These changes were reversed by supplementation with a vitamin mixture or vitamin E alone, whereas riboflavin or folic acid supplementation reduced the apoptotic rates, but only partially. Further, oxidative stress was the least in vitamin E- or vitamin mixture-supplemented rats and correlated well with their IEC apoptotic rates. Increased tissue oxidative stress seems to mediate the vitamin-restriction-induced apoptosis of the IECs in rats.
Vijayalakshhmi
Bodiga
B
Pathology Division, Naitonal Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad 500007, Andhra Pradesh, India.
Sesikeran
Boindala
B
Udaykumar
Putcha
P
Kalyanasundaram
Subramaniam
S
Raghunath
Manchala
M
D000818:Animals; D017304:Annexin A5; D000975:Antioxidants / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D001361:Avitaminosis / Q000178:diet therapy / Q000503:physiopathology*; D005492:Folic Acid / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000166:cytology*; D007583:Jejunum / Q000473:pathology; D007633:Keratins / Q000276:immunology / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012256:Riboflavin / Q000627:therapeutic use; D013194:Staining and Labeling; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein
D017304:Annexin A5; D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D017392:Thiobarbituric Acid Reactive Substances; D014815:Vitamins; D051028:bcl-2-Associated X Protein; D014810:Vitamin E; D007633:Keratins; D005492:Folic Acid; D012256:Riboflavin