There were two recent studies described below utilizing EagleBio’s Creatinine Microplate Assay, a kit designed for the quantitative determination of creatinine in urine by a microplate assay.This assay is part of our Oxidative Assay Kit Line which is a comprehensive group consisting of a numerous valuable products for assisting scientists in fields of research such as diabetes, cancer, aging, and other similar areas of study.
Authors: Alex E. Grill
Furan, a possible human carcinogen, is found in heat treated foods and tobacco smoke. Past studies have shown that humans are capable of converting furan to its reactive metabolite, cis-2-butene-1,4-dial (BDA), and thus may be susceptible to furan toxicity. Human risk assessment of furan exposure has been hindered because of the lack of mechanism-based exposure biomarkers.
In order to investigate this further, a study was performed at the University of Minnesota for evaluate six furan metabolites by measuring their levels in urine from furan-exposed rodents as well as in human urine from smokers and nonsmokers. The targets of this study were the metabolites that result from direct reaction of BDA with lysine (BDA-N(α)-acetyllysine) and from cysteine-BDA-lysine cross-links (N-acetylcyteine-BDA-lysine, N-acetylcysteine-BDA-Nα-acetyllysine and their sulfoxides. Researchers utilize Eagle Bioscience’s Creatinine Microplate Assay to measure creatinine in urine samples.
Five of the six metabolites were identified in urine from rodents treated with furan by gavage. BDA-N(α)-acetyllysine, N-acetylcysteine-BDA-lysine and its sulfoxide were detected in most human urine samples from three different groups. The levels of N-acetylcysteine-BDA-lysine sulfoxide were more than 10 times higher than the corresponding sulfide in many samples. The amount of this metabolite was higher in smokers relative to non-smokers and was significantly reduced following smoking cessation. Our results indicate a strong relationship between BDA-derived metabolites and smoking. Future studies will determine if levels of these biomarkers are associated with adverse health effects in humans.
Lung cancer is the leading cause of cancer death in the world and in order to have a better understanding of lung cancer susceptibility the different risks among smokers in varied ethnic groups needed to be evaluated.
The results of the Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. In addition, it was found that Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology.
Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA), respectively, are validated biomarkers of acrolein and crotonaldehyde exposure.The levels of 3-HPMA and HMPMA were quanified in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. Creatinine levels were analyzed using Eagle Bioscience’s Creatinine Microplate Assay to measure creatinine in urine samples.
In conclusion, the overall results of this study suggest that acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.
image above from Grill et. al cited above