Effect of Cadmium on the Peripheral Kynurenine Pathway in Rats
D. Pawlak1, M. Brzóska2, J. Moniuszko-Jakoniuk2, A. Stypułkowska3, K. Zwierz3
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1Department of Pharmacodynamics and 2Toxicology, Medical University, Mickiewicza 2C, 15-230 Białystok, Poland;
3Department of Pharmaceutical Biochemistry, Medical University, Mickiewicza 2A, 15-230 Białystok, Poland
Pol. J. Environ. Stud. 2005;14(4):501-507
This study investigated the kynurenine metabolism in rats treated with cadmium. We used an animal model at the levels of Cd corresponding to human environmental and occupational exposure to this metal which allows the assessment of its early effect on the structure and function of kidneys. We observed significant decrease in the serum concentration of tryptophan (TRP) and its metabolites: kynurenine (KYN), kynurenic acid (KYNA), and 3-hydroxykynurenine (3-HKYN), which was accompanied by a decrease in KYN derivatives in kidney and liver tissues. This effect was dependent on the level of Cd exposure. Regression analysis showed negative correlations between blood concentrations of Cd and TRP derivatives in serum, kidney and liver tissues.
Conversely, the urinary concentration of KYN and KYNA increased. Changes in product degradation of TRP after Cd treatment were proportional to the severity of renal damage and correlated with the concentration of proximal tubular injury marker - urinary isoenzyme B of N-acetyl-D-glucosaminidase (NAG-B).
Our results seem to indicate that intoxication with Cd induced significant disturbances in the peripheral kynurenine pathway.
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