Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity

Formaldehyde has been previously shown to play a dominant role in promoting synergy between doxorubicin (Dox) and formaldehyde-releasing butyric acid (BA) prodrugs in killing cancer cells. In this work, we report that these prodrugs also protect neonatal rat cardiomyocytes and adult mice against toxicity elicited by Dox. In cardiomyocytes treated with Dox, the formaldehyde releasing prodrugs butyroyloxymethyl diethylphosphate (AN-7) and butyroyloxymethyl butyrate (AN-1), but not the corresponding acetaldehyde-releasing butyroyloxydiethyl phosphate (AN-88) or butyroyloxyethyl butyrate (AN-11), reduced lactate dehydrogenase leakage, prevented loss of mitochondrial membrane potential (ΔΨm) and attenuated upregulation of the proapoptotic gene Bax. In Dox-treated mice, AN-7 but not AN-88 attenuated weight-loss and mortality, and increase in serum lactate dehydrogenase. These findings show that BA prodrugs that release formaldehyde and augment Dox anticancer activity also protect against Dox cardiotoxicity. Based on these observations, clinical applications of these prodrugs for patients treated with Dox warrant further investigation

Elevated serum levels of procollagen C‐proteinase enhancer‐1 in patients with chronic kidney disease is associated with a declining glomerular filtration rate

Background Procollagen C-proteinase enhancer-1 (PCPE-1) is a 55 kDa glycoprotein, which increases the activity of procollagen C-proteinases that break down C-terminal propeptides. Studies have shown that PCPE-1 is involved in the fibrotic process that occurs in various tissues and organs. Our review of the literature revealed no data concerning the relation between PCPE-1 and chronic kidney disease (CKD). The purpose of this study was to determine PCPE-1 levels in CKD. Methods One hundred thirty-one CKD patients and 34 healthy controls were included in our study. Demographic data were recorded, and routine biochemical tests were performed. Blood specimens were collected for PCPE-1 investigation. Demographic data, biochemical test results and PCPE-1 levels were compared between the control and patient groups. Parameters affecting PCPE-1 levels in our patient group were assessed. Results Procollagen C-proteinase enhancer-1 levels were significantly higher in our patient group compared to the control group. Parameters affecting PCPE-1 elevation in the patient group were identified as systolic blood pressure, blood urea nitrogen, phosphorus, haemoglobin, intact parathormone levels, glomerular filtration rate and body mass index. Conclusion We determined high PCPE-1 levels in CKD patients. PCPE-1 levels being negatively correlated with glomerular filtration rate suggests that PCPE-1 may be associated with progression in CKD patients