Combined supplementation of vanadium and beta-carotene suppresses placental glutathione S-transferase-positive foci and enhances antioxidant functions during the inhibition of diethylnitrosamine-induced rat liver carcinogenesis.
OBJECTIVE
The present study was designed to investigate the chemopreventive effects of combined vanadium (V; 0.5 p.p.m.) and beta-carotene (BC; 120 mg/kg of basal diet) on diethylnitrosoamine (DEN)-induced and phenobarbital (PB)-promoted rat hepatocarcinogenesis.


METHODS
All rats were subjected to two-thirds partial hepatectomy (PH) at the fourth week. After PH they were administered either trioctanoin alone (groups A', B', C' and D') or a single injection of DEN in trioctanoin at a dose of 10 mg/kg of body weight (groups A, B, C and D). Two weeks after the DEN treatment PB was administered (0.05% in basal diet) to all the DEN-treated rats and continued until the end of the experiment. Supplementation of V (groups B and B'), BC (groups C and C') or both V and BC (groups D and D') at the doses stated previously were started 4 weeks before DEN administration (at week 0) and continued until the 16th week.


RESULTS
It was observed that in the DEN-treated and PB-promoted group (group A) the expression of the numbers and areas of the placental form of glutathione S-transferase (GST-P)-positive altered hepatic foci (AHF) was maximum. Treatment with V (group B) and BC (group C) significantly reduced the expression of GST-P-positive AHF by 29.5% and 42.8%, respectively. An additive protection action (65.7%) was noticed in group D, which received both V and BC for the entire period of the experiment. It was also observed that supplementation of V and BC for the entire period of the experiment significantly reduced the number and size of the hyperplastic nodules, while the combination treatment worked as an additive effect, reducing the number and size of the hyperplastic nodules to 22% from 89%. Moreover, a significantly reduced level of cytosolic glutathione (P < 0.001) and glutathione-S-transferase (P < 0.001) activity and stabilization of aerobic metabolism and hepatic architecture of the cells as compared with carcinogen control were observed in the V + BC-treated group.


CONCLUSIONS
The present study suggests that V, an essential trace element, may be useful in combination with BC, an antioxidant, in the inhibition of experimentally induced rat hepatocarcinogenesis.
Chattopadhyay
Mitali Basu
MB
Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
C B
Mahendra Kumar
MK
Kanna
P Suresh
PS
Ray
Rajarshi Sankar
RS
Roy
Souvik
S
Chatterjee
Malay
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004052:Diethylnitrosamine; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014639:Vanadium / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
D000975:Antioxidants; D014639:Vanadium; D019207:beta Carotene; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D005978:Glutathione