Objective Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,β-unsaturated aldehyde, is a common dietary and environmental pollutant. Design The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models. Methods Acrolein-conjugated proteins (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin-angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system. Results We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathway, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function. Conclusions These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.

Scope Acrolein is a highly electrophilic α,β‐unsaturated aldehyde and is associated with human diseases. It is formed by Maillard reaction during food processing and could be detected in the emissions of overheated cooking oils. Consequently, humans are at risk of acrolein exposure through consumption of such prepared food. Methods and results We conducted three human studies that healthy subjects (21–30 years) were served fried foods including fried chicken and French fries from three commercial fast food restaurants. Acrolein‐related metabolites including urinary 3‐hydroxypropyl mercapturic acid (3‐HPMA), serum acrolein‐protein conjugates (Acr‐FDP), and buccal acrolein‐induced DNA damages (Acr‐dG adducts) along with GSH levels in serum or buccal cells were investigated for different times after consumption. Conclusion Urinary 3‐HPMA levels were increased after 2‐hr consumption of fried food with an elimination half‐life of 10 hr. In addition, increased Acr‐dG adducts in oral cavity were inversely correlated to buccal glutathione (GSH) levels after consumption. However, there was no significant change in systemic GSH levels or Acr‐FDP adducts in serum. These results indicate that exposure of acrolein from consuming fried food affects local oral cavity homeostasis. This may provide a possible link between intake of fried food and increased risk of upper aerodigestive tract cancers.

No abstract

Glioblastoma (GBM), the most lethal type of brain tumor in adults, has considerable cellular heterogeneity. The standard adjuvant chemotherapeutic agent for GBM, temozolomide (TMZ), has a modest response rate due to the development of drug resistance. Multiple studies have shown that valproic acid (VPA) can enhance GBM tumor control and prolong survival when given in conjunction with TMZ. However, the beneficial effect is variable. In this study, we analyzed the impact of VPA on GBM patient survival and its possible correlation with TMZ treatment and p53 gene mutation. In addition, the molecular mechanisms of TMZ in combination with VPA were examined using both p53 wild-type and p53 mutant human GBM cell lines. Our analysis of clinical data indicates that the survival benefit of a combined TMZ and VPA treatment in GBM patients is dependent on their p53 gene status. In cellular experiments, our results show that VPA enhanced the antineoplastic effect of TMZ by enhancing p53 activation and promoting the expression of its downstream pro-apoptotic protein, PUMA. Our study indicates that GBM patients with wild-type p53 may benefit from a combined TMZ+VPA treatment.