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AIM:To investigate if cisplatin alters vitamin status andif VR modulates cisplatin induced intestinal apoptosis andoxidative stress in Wistar/NIN(WNIN)male rats.METHODS:Weanling,WNIN male rats(n=12 pergroup)received adlibitum for 17 wk:control diet(20%protein)or the same with 50% vitamin restriction.Theywere then sub-divided into two groups of six rats eachand administered cisplatin(2.61 mg/kg bodyweight)once a week for three wk or PBS(vehicle control).Intestinal epithelial cell(IEC)apoptosis was monitoredby morphometry,Annexin-V binding,M30 cytodeathassay and DNA fragmentation.Structural and functionalintegrity of the villus were assessed by villus height/crypt depth ratio and activities of alkaline phosphatase,lys,ala-dipeptidyl amino-peptidase,respectively.Toassess the probable mechanism(s)of altered apoptosis,oxidative stress parameters,caspase-3 activity,andexpression of Bcl-2 and Bax were determined.RESULTS:Cisplatin per se decreased plasma vitaminlevels and they were the lowest in VR animals treatedwith cisplatin.As expected VR increased only villusapoptosis,whereas cisplatin increased stem cellapoptosis in the crypt.However,cisplatin treatmentof VR rats increased apoptosis both in villus and cryptregions and was associated with higher levels of TBARS,protein carbonyls and caspase-3 activity,but lower GSHconcentrations.VR induced decrease in Bcl-2 expression was further lowered by cispiatin.Bax expression,unaffected by VR was increased on cisplatin treatment.Mucosal functional integrity was severely compromisedin cisplatin treated VR-rats.CONCLUSION:Low intake of vitamins increases thesensitivity of rats to cisplatin and promotes intestinalepithelial cell apoptosis.
AIM: To investigate if cisplatin alters vitamin status andif VR modulates cisplatin induced intestinal apoptosis and oxidative stress in Wistar / NIN (WNIN) male rats. METHODS: Weanling, WNIN male rats (n = 12 pergroup) received adlibitum for 17 wk: control diet ( 20% protein) or the same with 50% vitamin restriction. Theywere then sub-divided into two groups of six rats eachand administered cisplatin (2.61 mg / kg bodyweight) once a week for three wk or PBS (vehicle control) .Intestinal epithelial cells (IEC) apoptosis was monitored by morphometry, Annexin-V binding, M30 cytodeathassay 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, . Toassess the probable mechanism (s) of altered apoptosis, oxidative stress parameters, caspase-3 activity, andexpression 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 villusapoptosis, cisplatin increased stem cellapoptosis in the crypt. However, cisplatin treatment of VR rats increased apoptosis both in villus and cryptregions and was associated with higher levels of TBARS, protein carbonyls and caspase-3 activity, but lower GSH concentration.VR induced decrease in Bcl-2 expression was lowered lower by cispiatin.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 thesensitivity of rats to cisplatin and promotes intestinalepithelial cell apoptosis.