ABSTRACT
OBJECTIVE: N,N-dimethylformamide (DMF) exerts anti-inflammatory and anti-oxidant capacities. We aim to explore whether DMF could regulate cisplatin-induced kidney injury in rats via NF-E2-related factor 2 (Nrf2) pathway and nuclear factor-κB (NF-κB) pathway. MATERIALS AND METHODS: A total of 30 Sprague Dawley (SD) rats were randomly assigned into sham group, cisplatin treatment group (DDP group) and DMF + cisplatin treatment group (DMF group), with 10 rats in each group. After 10 days of treatment, we collected serum and kidney samples of rats. Serum levels of creatinine (Cr) and urea nitrogen (BUN) were detected using relative commercial kits. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of kidneys. The relevant oxidative stress indicators in the kidney homogenates of each group were detected by commercial kits, including malondialdehyde (MDA), total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and monoamine oxidase (MAO). Protein expressions of Nrf2 and NF-κB in kidney tissues were detected by Western blot. RESULTS: Serum levels of Cr and BUN were lower in DMF group than those of DDP group. Higher activities of SOD, GSH, CAT and T-AOC were found in DMF group compared with those of DDP group. However, MAD and ROS contents were remarkably decreased in DMF group than those of DDP group. DMF pretreatment remarkably reduced renal pathological changes. Western blot analysis also indicated that DMF effectively upregulated expression levels of Nrf2, Heme Oxygenase-1 (HO-1) and NAD (P) H, quinine oxidoreductase 1 (NQO-1), while downregulated NF-κB. CONCLUSIONS: DMF could inhibit oxidative stress by activating Nrf2 signaling pathway and reduce inflammatory response by attenuating NF-κB signaling pathway, thus protecting cisplatin-induced kidney injury.
Subject(s)
Acute Kidney Injury/prevention & control , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Dimethylformamide/pharmacology , Inflammation Mediators/metabolism , Kidney/drug effects , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Cisplatin , Disease Models, Animal , Kidney/metabolism , Kidney/pathology , Neutrophil Infiltration/drug effects , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Ruminants are an important reservoir of Escherichia coli O157:H7. To reduce E coli O157:H7 excretion by these animals could play a key role in prevention and control of human infections. In the present study, the authors used 12 three-month-old goats to evaluate the efficacy of intranasal administration of the Stx2B-Tir-Stx1B-Zot protein. These goats were inoculated on days 0 and 21 and infected with 10(10) colony-forming units (cfu) of E coli O157:H7 by oral inoculation on day 36. Faecal shedding was monitored daily for two weeks. All of six goats immunised with recombinant protein elicited significant Stx2b-Tir-Stx1b-Zot-specific serum IgG antibodies, and three of them also showed production of antigen-specific IgA in faeces. The immunised goats showed much less shedding of E coli O157:H7 after challenge. These results demonstrate the potential for the use of Stx2B-Tir-Stx1B-Zot protein in mucosal vaccine formulations to prevent colonisation and shedding of E coli O157:H7 in goats.