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Diabetic nephropathy is strongly associated with both increased oxidative stress and kidney tissue hypoxia. The increased oxidative stress causes increased kidney oxygen consumption resulting in kidney tissue hypoxia. To date, it has been difficult to determine the role of kidney hypoxia, per se, for the development of nephropathy. We tested the hypothesis that kidney hypoxia, without confounding factors such as hyperglycemia or elevated oxidative stress, results in nephropathy. To induce kidney hypoxia, dinitrophenol (30 mg per day per kg bodyweight by gavage), a mitochondrial uncoupler that increases oxygen consumption and causes kidney hypoxia, was administered for 30 consecutive days to rats. Thereafter, glomerular filtration rate, renal blood flow, kidney oxygen consumption, kidney oxygen tension, kidney concentrations of glucose and glycogen, markers of oxidative stress, urinary protein excretion, and histological findings were determined and compared with vehicle-treated controls. Dinitrophenol did not affect arterial blood pressure, renal blood flow, glomerular filtration rate, blood glucose, or markers of oxidative stress but increased kidney oxygen consumption, and reduced cortical and medullary concentrations of glucose and glycogen, and resulted in intrarenal tissue hypoxia. Furthermore, dinitrophenol treatment increased urinary protein excretion, kidney vimentin expression, and infiltration of inflammatory cells. In conclusion, increased mitochondrial oxygen consumption results in kidney hypoxia and subsequent nephropathy. Importantly, these results demonstrate that kidney tissue hypoxia, per se, without confounding hyperglycemia or oxidative stress, may be sufficient to initiate the development of nephropathy and therefore demonstrate a new interventional target for treating kidney disease. [ABSTRACT FROM AUTHOR]

2,4-Dinitrophenol (2,4-DNP), a yellowish compound, has historically been used in the manufacture of dyes, explosives, and fungicides. As it uncouples mitochondrial oxidative phosphorylation, the compound was also used as an antiobesity agent early in the past century. The compound was subsequently banned by the United States Food and Drug Administration in 1938 due to its potentially fatal adverse effects, including hyperthermia, cataract, agranulocytosis, hepatoxicity, nephrotoxicity, and cardiotoxicity. However, the popularity of 2,4-DNP as a slimming aid has appeared to increase again in recent years. The Hong Kong Hospital Authority Toxicology Reference Laboratory recently confirmed two cases of self-administered 2,4-DNP with different clinical presentations to hospitals in the area. Here we describe those two cases, in an attempt to underscore the potential of misuse of this substance by body-conscious groups among the Chinese population. [ABSTRACT FROM AUTHOR]