Modulation of fatty acid methyl esters in rats pretreated with tri-o-tolyl phosphate

Research output: Contribution to journalArticle

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Abstract

Formation and toxicity of fatty acid methyl esters (FAMEs) have been reported both in vitro and in vivo. In previous studies, it was shown that fatty acid ethyl ester synthase (FAEES), which catalyzes the formation of FAMEs, also expresses esterase activity. Therefore, it was hypothesized that inhibitors of esterases such as tri-o-tolyl phosphate (TOTP) can modulate the formation of FAMEs. To test this, four groups of rats were used. Group 1 served as control (vehicle only). Group 2 was treated with methanol only (3 g/kg via gavage), group 3 was given TOTP only (100 mg/kg ip in corn oil), and group 4 was administered TOTP as in group 3, followed by methanol after 18 h. Three hours after exposure, animals were sacrificed and FAEES activity and FAME levels were measured in blood, liver, pancreas, and brown fat. About 95% of FAEES activity was inhibited in the liver and whole blood of TOTP-treated rats (group 3) but no inhibition was observed in the pancreas or brown fat. Total hepatic FAMEs were found to be lowest for the TOTP-treated group (3) and highest in the methanol-treated animals (group 2). Total pancreatic FAMEs in different groups were not statistically different, while significant increases were observed in the brown fat in both methanol-treated groups. To verify that the oxidative metabolism of methanol was unaffected by TOTP, alcohol dehydrogenase activity was also measured and found to be unchanged in any group as compared to control. These results demonstrate that the formation of FAMEs can be modulated in the liver and probably in blood, but not in the pancreas or brown fat by the inhibitors of FAEES.

Original languageEnglish (US)
Pages (from-to)583-593
Number of pages11
JournalJournal of Toxicology and Environmental Health - Part A
Volume67
Issue number7
StatePublished - Apr 9 2004

Fingerprint

Fatty acids
ester
Rats
Esters
Phosphates
Fatty Acids
fatty acid
Modulation
phosphate
Brown Adipose Tissue
Methanol
Fats
Liver
methanol
Oils and fats
Pancreas
Blood
fat
Esterases
Animals

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health
  • Pollution
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Modulation of fatty acid methyl esters in rats pretreated with tri-o-tolyl phosphate. / Mericle, Kelly A.; Kaphalia, Bhupendra; Ansari, Ghulam.

In: Journal of Toxicology and Environmental Health - Part A, Vol. 67, No. 7, 09.04.2004, p. 583-593.

Research output: Contribution to journalArticle

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abstract = "Formation and toxicity of fatty acid methyl esters (FAMEs) have been reported both in vitro and in vivo. In previous studies, it was shown that fatty acid ethyl ester synthase (FAEES), which catalyzes the formation of FAMEs, also expresses esterase activity. Therefore, it was hypothesized that inhibitors of esterases such as tri-o-tolyl phosphate (TOTP) can modulate the formation of FAMEs. To test this, four groups of rats were used. Group 1 served as control (vehicle only). Group 2 was treated with methanol only (3 g/kg via gavage), group 3 was given TOTP only (100 mg/kg ip in corn oil), and group 4 was administered TOTP as in group 3, followed by methanol after 18 h. Three hours after exposure, animals were sacrificed and FAEES activity and FAME levels were measured in blood, liver, pancreas, and brown fat. About 95{\%} of FAEES activity was inhibited in the liver and whole blood of TOTP-treated rats (group 3) but no inhibition was observed in the pancreas or brown fat. Total hepatic FAMEs were found to be lowest for the TOTP-treated group (3) and highest in the methanol-treated animals (group 2). Total pancreatic FAMEs in different groups were not statistically different, while significant increases were observed in the brown fat in both methanol-treated groups. To verify that the oxidative metabolism of methanol was unaffected by TOTP, alcohol dehydrogenase activity was also measured and found to be unchanged in any group as compared to control. These results demonstrate that the formation of FAMEs can be modulated in the liver and probably in blood, but not in the pancreas or brown fat by the inhibitors of FAEES.",
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