Hippurate metabolism as a hydroxyl radical trapping mechanism in the rat kidney.
Hippurate (Hip) is considered to be the end product of benzoate (BA) metabolism. However, the kidney is able to metabolize Hip. Although only Hip but no BA is present in the blood, rat urine contains under normal conditions less Hip (about 0.4 mM) than BA (about 4.5 mM) and of hydroxylated derivatives of BA (hydroxy-BAs = HB and dihydroxy-BAs = DHB). Generation of HBs and DHBs is the result of radical substitution by free OH radicals (*OH). Thus, rate of synthesis of HBs and DHBs may reflect the production rate of *OH in the kidney *OH generation is elevated following ischemic stress. Therefore, production of HBs and DHBs can be expected to be elevated in postischemic injury. The validity of this assumption was tested in vitro on isolated tubular segments and in vivo in the rat. Metabolism of Hip at 0.1 mmol x l(-1 ) (0.1 mM) as well as of BA resulted in enlarged production of both HBs (especially 3-HB and 4-HB) and of DHBs (especially 2,6-DHB). Production of 2,3- and especially of 2,5-DHB was elevated in the presence of high concentration (1.0 mM) of salicylate (2-HB) only. In vivo both in acute (120 min) and in chronic (5 days) experiments ligation of one renal artery for 30 respectively 60 min resulted in enlarged excretion of HBs and DHBs, especially of 2,6- and 3,5-DHB. This finding is noteworthy since (a) formation of 2,6-DHB necessitates as precursor salicylate which could not be detected in our experiments and (b) the spontaneous attack of *OH upon the benzol ring would prefer the positions 2,3- 2,5- and 3,4-. Therefore, the existence of regulating factor(s) guiding OH groups to definite positions is a distinct possibility. These results indicate that metabolism of Hip leading to hydroxylated BAs may be a renoprotective mechanism against attack of *OH in reoxygenated renal tissue.
Mályusz
M
M
Department of Physiology, University of Kiel, Germany. m.malyusz@physiologie.uni-kiel.de
Kähler
W
W
Gronow
G
G
D000818:Animals; D006626:Hippurates / Q000378:metabolism*; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation
D006626:Hippurates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C030514:hippuric acid