Home banner
Divider
A-Z Index

Quick way to the find the information that you need...

More button
Register with FRAME

Although you do not need to register, any information you provide will be confidential and used only by FRAME to improve the website

Register button
Account Login
Forgot password?

ATLA - ISI
The Journal

 

Alternatives to Laboratory Animals - ATLA

Download latest issue button Download back issues button Subscribe to ATLA
Contact Us

Tel icon

Tel: +44 (0)115 9584740


Tel icon

Fax: +44 (0)115 9503570

Make an Enquiry

Haloalcohols deplete glutathione when incubated with fortified liver fractions.


Garle,M.J., Sinclair, C., Thurley P. and Fry, J.R.

Xenobiotica, 29(5), 533 - 545 (1999).

This study has examined the ability of dichloropropanols, haloalcohols and their putative metabolites to deplete glutathione when incubated with liver fractions obtained from untreated and differentially induced rats. 2. 1,3-Dichloropropan-2-ol and 2,3-dichloropropan-1-ol (0-1000 muM) both depleted glutathione in a dose-dependent manner when incubated with cofactors (NADPH generating system) and liver microsomes from the untreated rat. 3. The extent of GSH depletion was significantly enhanced when liver microsomes from the isoniazid- or isosafrole-treated rat were used. 4. Epichlorohydrin produced a moderate, dose-dependent depletion of GSH. By contrast, 1,3-dichloroacetone (identified by TLC as a metabolite of 1,3-dichloropropanol) was a potent depletor of glutathione. 5. N-acetylcysteine was less efficient than glutathione as a nucleophile trap for epichlorohydrin, 1,3-dichloroacetone or reactive metabolites derived from 1,3-dichloropropan-2-ol. 6. 1,3-Dibromopropan-2-oland 1,4-dibromobutan-2-ol were potent depletors of GSH but 1-bromopropan-2-ol produced less GSH depletion. Both dibromoalcohols depleted GSH when incubated with dialysed cytosol derived from the livers of untreated rats. 7. The GSH depletion mediated by 1,3-dichloropropan-2-ol, 1,3-dibromopropan-2- ol, 1,4-dibromobutan-2-ol and 1-bromopropan-2-ol was inhibited by inclusion of pyridine (1 mM) or cofactor omission. 1,3-Difluoropropanol did not deplete GSH under any of the conditions examined.