Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury.

Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement. Region-specific changes (e.g., medulla and cortex) in metabolites related to DNA damage and energy generation were observed over the 72-h exposure period. Therefore, this metabolomics approach may become a novel strategy for elucidating early renal responses to cisplatin, prior to the detection of kidney damage evaluated by conventional method.

Nifedipine treatment reduces brain damage after transient focal ischemia, possibly through its antioxidative effects.

Stroke is a major cause of mortality and morbidity in hypertensive patients. This study investigated the effects of nifedipine, an L-type voltage-gated Ca(2+) channel blocker, on ischemic lesion volume after focal cerebral ischemia and reperfusion in rats. Rats were subjected to 1 h of transient middle cerebral artery occlusion (MCAO). At 2 days after MCAO, the rats were randomized into two groups that were fed either a normal control diet (n=10) or a nifedipine (0.001%) containing diet (n=11) for 2 weeks. Nifedipine treatment significantly reduced ischemic lesion volume (116.5 ± 10.8 vs. 80.0 ± 8.2 mm(3), P < 0.05) without affecting body weight or blood pressure. It also decreased thiobarbituric-reactive substances, an index of lipid peroxide, (2.6 ± 0.4 vs. 1.7 ± 0.1 µmol g(-1) tissue, P < 0.05) and increased glutathione peroxidase (54.9 ± 4.7 vs. 70.9 ± 6.4 U g(-1) protein, P < 0.05) and glutathione reductase activities (32.4 ± 1.4 vs. 39.9 ± 2.7 U g(-1) protein, P < 0.05) in the mitochondria from the ischemic hemispheres. These results suggest that nifedipine treatment can reduce ischemic lesion volume after focal cerebral ischemia, possibly because of the decrease in oxidative stress with an increase in antioxidant activities within the ischemic area.