PMID- 9332170
OWN - NLM
STAT- MEDLINE
DCOM- 19971120
LR  - 20061115
IS  - 0019-5189 (Print)
IS  - 0019-5189 (Linking)
VI  - 35
IP  - 3
DP  - 1997 Mar
TI  - Effects of silymarin on UDP-glucuronic acid and glucuronidation activity in the 
      rat isolated hepatocytes and liver in relation to D-galactosamine toxicity.
PG  - 256-63
AB  - Influence of silymarin on UDP-glucuronic acid (UDPGA) and glucuronidation 
      activity of freshly isolated rat hepatocytes in suspension and in rat liver in 
      vivo was examined. Viability of the hepatocytes (> 85%) was not altered in Hank's 
      balanced salt solution at least for 4 hr at 37 degrees C under oxygen. Silymarin 
      at 0.4 mM depleted UDPGA by more than 60% at the end of 4 hr of incubation, the 
      fall in nucleotide pool was rapid and concentration (0.1-0.4 mM)-dependent. The 
      rate of glucuronidation of 3-OH- benzo(a)pyrene (3-OH-BP) determined 
      simultaneously was also reduced significantly; silybin being 3-times more 
      effective than silymarin. Combination of flavonoids with D-galactosamine (GalN) 
      further attenuated the glucuronidation functions of the cells. The flavonoids 
      also offered strong inhibition of UDP-glucose dehydrogenase (UDP-GDH) activity in 
      the liver cytosolic fraction while the activity in hepatocytes was not affected 
      even after 4 hr of incubation. Interestingly, the GalN- induced strong inhibition 
      of UDP-GDH in isolated hepatocytes was completely abolished by flavonoids. 
      Decrease in UDPGA appeared neither due to the activation of UDPGA-pyrophosphatase 
      activity nor to the inhibition of UDP-GDH activity in hepatocytes. Further, the 
      flavonoids also inhibited hepatic UDP-glucuronyltransferase activity towards 
      3-OH-BP (UGT) both in vitro and in intact cells. On the contrary, silymarin 
      administered (70 mg/kg body wt; i.p.) to rats for 3 hr increased the hepatic 
      UDPGA by 2-fold while GalN (400 mg/kg body wt) reduced the nucleotide content to 
      50% of control. Coadministration of silymarin and GalN restored the UDPGA content 
      significantly while the activities of UDP-GDH and UGT were comparable to the 
      untreated control. The results indicated that silymarin elicits differential 
      effects on the rate of glucuronidation and contents of UDPGA in the isolated rat 
      hepatocytes and in liver. The flavonoid counteracted D-GalN-induced lowering of 
      UDPGA presumably by relieving UDP-GDH of in vivo inhibition affected by 
      GalN-metabolite.
FAU - Chrungoo, V J
AU  - Chrungoo VJ
AD  - Biochemistry Section, Regional Research Laboratory (C.S.I.R.), Jammu, India.
FAU - Reen, R K
AU  - Reen RK
FAU - Singh, K
AU  - Singh K
FAU - Singh, J
AU  - Singh J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - India
TA  - Indian J Exp Biol
JT  - Indian journal of experimental biology
JID - 0233411
RN  - 0 (Silymarin)
RN  - 2616-64-0 (Uridine Diphosphate Glucuronic Acid)
RN  - 7535-00-4 (Galactosamine)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
SB  - IM
MH  - Animals
MH  - Galactosamine/*toxicity
MH  - Glucuronosyltransferase/*metabolism
MH  - Liver/cytology/*drug effects/metabolism
MH  - Male
MH  - Rats
MH  - Silymarin/*pharmacology
MH  - Uridine Diphosphate Glucuronic Acid/*metabolism
EDAT- 1997/03/01 00:00
MHDA- 1997/10/23 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/10/23 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
PST - ppublish
SO  - Indian J Exp Biol. 1997 Mar;35(3):256-63.