Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 21, 2006; 12(7): 1078-1085
Published online Feb 21, 2006. doi: 10.3748/wjg.v12.i7.1078
Chronic low vitamin intake potentiates cisplatin-induced intestinal epithelial cell apoptosis in WNIN rats
Bodiga Vijayalakshmi, Boindala Sesikeran, Putcha Udaykumar, Subramaniam Kalyanasundaram, Manchala Raghunath
Bodiga Vijayalakshmi, Boindala Sesikeran, Putcha Udaykumar, Department of Pathology, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania, Hyderabad - 500 007, Andhra Pradesh, India
Subramaniam Kalyanasundaram, National Center for Laboratory Animal Sciences, National Institute of Nutrition, Jamai Osmania, Hyderabad - 500 007, Andhra Pradesh, India
Manchala Raghunath, Endocrinology and Metabolism Division, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania, Hyderabad - 500007 Andhra Pradesh, India
Supported by The Indian Council of Medical Research
Correspondence to: Dr. Manchala Raghunath, National Institute of Nutrition, Hyderabad - 500007, Andhra Pradesh, India.
Telephone: +91-40-27008921 Fax: +91-40-27019074
Received: July 1, 2005
Revised: July 2, 2005
Accepted: August 26, 2005
Published online: February 21, 2006

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.

Keywords: Apoptosis, Cisplatin, Intestinal epithelium, Mucosal integrity, Oxidative stress, Vitamins.