Biochemistry & Analytical Biochemistry

Chemical N-nitrosation of metaprim [(5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine] prophylactic dose regime and the toxicological consequences in rats fed diets containing varying levels of protein of the derivable n

Global Congress on Biochemistry, Glycomics & Amino Acids

December 08-09, 2016 San Antonio, USA

Oladele F W, Akanni I B, Adimekwe N F, Ogungbuji T E, Olayemi Oludairo E and Maduagwu E N

Covenant University, Nigeria

Posters & Accepted Abstracts: Biochem Anal Biochem

Abstract:

A 50 gm portion of metaprim [(5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine] was nitrosated and the nitrosamine formed were identified qualitatively and quantitatively, before calculating the amount measuring to an adult metaprim prescribed regimen of 25 mg per week, and using the pure compound for toxicity studies in rats fed diets containing varying levels of protein. Twenty four 130 gm rats in six animals per group were fed with semi-purified diets of 18% normal-proteindiet; 8% low-protein-diet; 64% high-protein-diet; or 0% protein-free-diet, with drinking water ad libitum for 14 days, before dosing orally with 0.1 mg authentic nitrosamine, sacrificing in extremis and conducting liver function tests, urine nitrite analysis, liver histopathology, in vitro metabolisms, and identifying formed nitrosamine by double-dimensional thin-layerchromatography, using reference pure nitrosamine, recommended color spray reagents and UV irradiation (240 nm). N-Nitrosodimethylamine (NDMA) was detected. There was a significant increase in mean nitrite content of urine of the highprotein- diet rats (0.083 mg/ml) and a lower level in either the low-protein or protein-free-diet animals (0.010 and 0.001 mg/ml, respectively), compared to normal-protein-diet rats (0.003mg/ml). A higher increase in nitrite was found on exposure to UV irradiation, thereby indicating presence of a nitrosamine in voided urine. There were significant increases (P< 0.05) in ALT and AST levels of serum (81.47±7.91 and 204.15±22.33 IU/L, respectively) in the high-protein-fed rats. The direct serum bilirubin of both the low-protein and protein-free-diet rats were much increased. A mild liver lobular inflammation and accumulation of mononuclear cells in the perivascular area was seen in the high-protein-diet rats. In vitro degradation of NDMA increased in the high-protein-diet rats and decreased in lower-protein-diet species, as compared to normal-protein-diet rats. Metaprim is an exogenous source of NDMA, and its endogenous nitrosation is likely to cause mild toxicity to liver, preventable by a lowprotein- diet and accentuated by high-protein-diet intake.

Biography :

Email: oladelefoluke55@yahoo.com