PMID- 7503757
OWN - NLM
STAT- MEDLINE
DCOM- 19960117
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 50
IP  - 10
DP  - 1995 Nov 9
TI  - Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat.
PG  - 1557-65
AB  - Parameters related to hepatic oxidative stress, cell injury, phagocytic activity, 
      and liver histology were studied in control rats and in animals subjected to 
      L-3,3',5-triiodothyronine (T3) and/or lindane administration. Hyperthyroidism 
      elicited a calorigenic response and increased rates of hepatic O2 uptake, which 
      were not modified by lindane treatment. T3 diminished serum lindane levels as 
      well as those in the liver and adipose tissue, whereas lindane enhanced serum T3 
      levels in animals given T3. Compared with control rats, lindane significantly 
      increased the rate of formation of thiobarbituric acid reactants (TBARS) by the 
      liver, with no changes in either the reduced glutathione (GSH) content, the 
      TBARS/GSH ratio as indicator of oxidative stress, or in the fractional rates of 
      lactate dehydrogenase (LDH) and GSH efflux from perfused livers as integrity 
      parameters. Hyperthyroidism induced GSH depletion in the liver, with a 
      significant enhancement in the TBARS formation, the TBARS/GSH ratio, and in the 
      fractional LDH and GSH efflux. These parameters were increased further by joint 
      T3 and lindane administration in a magnitude exceeding the sum of the effects 
      produced by the separate treatments. In addition, hyperthyroidism led to Kupffer 
      cell hyperplasia and significant increases in serum glutamate oxalacetate 
      transaminase (GOT) and in hepatic zymosan-induced chemiluminescence, while liver 
      myeloperoxidase (MPO) activity was found unchanged, compared with controls. Rats 
      treated with lindane presented normal liver histology, with no changes in 
      biochemical parameters related to cell injury. The joint administration of T3 and 
      lindane, however, elicited a marked elevation in serum GOT and glutamate pyruvate 
      transaminase (GPT), concomitantly with extensive liver necrosis and the presence 
      of granulomas containing lymphocytes, Kupffer cells and polymorphonuclear 
      leukocytes (PMN). In this condition, hepatic zymosan-induced light emission and 
      MPO activity were enhanced over control values. It is concluded that 
      hyperthyroidism increases the susceptibility of the liver to the toxic effects of 
      lindane, which seems to be accomplished by potentiation of the hepatic oxidative 
      stress status. The latter effect may be conditioned by an enhanced phagocytic 
      respiratory burst activity due to the observed Kupffer cell hyperplasia and PMN 
      infiltration, in addition to the increased production of reactive oxygen species 
      in parenchymal cells.
FAU - Videla, L A
AU  - Videla LA
AD  - Departamento de Bioqimica, Facultad de Medicina, Universidad de Chile, Santiago, 
      Chile.
FAU - Smok, G
AU  - Smok G
FAU - Troncoso, P
AU  - Troncoso P
FAU - Simon, K A
AU  - Simon KA
FAU - Junqueira, V B
AU  - Junqueira VB
FAU - Fernandez, V
AU  - Fernandez V
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 59NEE7PCAB (Hexachlorocyclohexane)
RN  - 9010-72-4 (Zymosan)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - *Chemical and Drug Induced Liver Injury
MH  - Glutathione/metabolism
MH  - Hexachlorocyclohexane/*toxicity
MH  - Hyperthyroidism/chemically induced/metabolism/*physiopathology
MH  - Kupffer Cells/drug effects/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Liver/cytology/drug effects/metabolism
MH  - Liver Diseases/metabolism
MH  - Luminescent Measurements
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Microscopy
MH  - Neutrophils/drug effects/metabolism
MH  - Oxidative Stress/physiology
MH  - Peroxidase/metabolism
MH  - Phagocytes/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Triiodothyronine/blood/toxicity
MH  - Zymosan/pharmacology
EDAT- 1995/11/09 00:00
MHDA- 1995/11/09 00:01
CRDT- 1995/11/09 00:00
PHST- 1995/11/09 00:00 [pubmed]
PHST- 1995/11/09 00:01 [medline]
PHST- 1995/11/09 00:00 [entrez]
AID - 000629529502025X [pii]
AID - 10.1016/0006-2952(95)02025-x [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1995 Nov 9;50(10):1557-65. doi: 10.1016/0006-2952(95)02025-x.