Increased Accumulation of Protein-Bound Nε-(Carboxymethyl)lysine in Tissues of Healthy Rats after Chronic Oral Nε-(Carboxymethyl)lysine

Abstract

In recent years, chronic diseases related to advanced glycation end products (AGEs) have attracted more attention. Because diet is an important exogenous source of AGEs, this study aimed to investigate the effects of chronic oral administration of pure N(ε)-(carboxymethyl)lysine (CML) (a major AGE) at 60 mg kg(-1) per day on healthy Sprague-Dawley rats. After administration for 12 weeks, the levels of protein-bound CML were increased to 202 ± 17, 167 ± 47, 217 ± 44, 107 ± 4, 144 ± 23, and 33 ± 7 μg/g dry matter in the kidneys, heart, liver, lungs, spleen, and pancreas, respectively, in comparison with control values of 98 ± 1, 90 ± 15, 140 ± 42, 76 ± 18, 115 ± 15, and 30 ± 4 μg/g dry matter. The difference was significant (p < 0.05) for the kidneys, heart, liver, and lungs, whereas no significant increase was seen in the spleen and pancreas. Furthermore, serum blood urea nitrogen (BUN), creatinine (CREA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values increased significantly (p < 0.05), as evidence of impaired kidney and liver function. Additionally, the rats' fasting blood glucose (FBG) levels remained within the normal range, indicating that chronic intake of CML does not promote a rise in blood glucose. These results clearly indicate that a CML-rich diet might be a potential health risk in humans, particularly with respect to kidney and liver function.