The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

Oxidative stress is an important mechanism of injury in chronic kidney disease. Potential pathways of oxidative stress mediating kidney injury are discussed. ABSTRACT:n ep_1572 311..321Chronic kidney disease (CKD) is a common and serious problem that adversely affects human health, limits longevity and increases costs to health-care systems worldwide. Its increasing incidence cannot be fully explained by traditional risk factors. Oxidative stress is prevalent in CKD patients and is considered to be an important pathogenic mechanism. Oxidative stress develops from an imbalance between free radical production often increased through dysfunctional mitochondria formed with increasing age, type 2 diabetes mellitus, inflammation, and reduced anti-oxidant defences. Perturbations in cellular oxidant handling influence downstream cellular signalling and, in the kidney, promote renal cell apoptosis and senescence, decreased regenerative ability of cells, and fibrosis. These factors have a stochastic deleterious effect on kidney function. The majority of studies investigating anti-oxidant treatments in CKD patients show a reduction in oxidative stress and many show improved renal function. Despite heterogeneity in the oxidative stress levels in the CKD population, there has been little effort to measure patient oxidative stress levels before the use of any anti-oxidants therapies to optimize outcome. This review describes the development of oxidative stress, how it can be measured, the involvement of mitochondrial dysfunction and the molecular pathways that are altered, the role of oxidative stress in CKD pathogenesis and an update on the amelioration of CKD using anti-oxidant therapies.

Chronic kidney disease (CKD) is a major public health problem. The classification of CKD by KDOQI and KDIGO and the routine eGFR reporting have resulted in increased identification of CKD. It is important to be able to identify those at high risk of CKD progression and its associated cardiovascular disease (CVD). Proteinuria is the most sensitive marker of CKD progression in clinical practice, especially when combined with eGFR, but these have limitations. Hence, early, more sensitive, biomarkers are required. Recently, promising biomarkers have been identified for CKD progression and its associated CVD morbidity and mortality. These may be more sensitive biomarkers of kidney function, the underlying pathophysiological processes, and/or cardiovascular risk. Although there are some common pathways to CKD progression, there are many primary causes, each with its own specific pathophysiological mechanism. Hence, a panel measuring multiple biomarkers including disease-specific biomarkers may be required. Large, longitudinal observational studies are needed to validate candidate biomarkers in a broad range of populations prior to implementation into routine CKD management. Recent renal biomarkers discovered include neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and liver-type fatty acid-binding protein. Although none are ready for use in clinical practice, it is timely to review the role of such biomarkers in predicting CKD progression and/or CVD risk in CKD.

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The results suggest that, in addition to its well-known erythropoietic effects, EPO inhibits apoptotic cell death, enhances tubular epithelial regeneration and promotes renal functional recovery in hypoxic or ischaemic acute renal injury.

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The pathogenesis of heat-induced cell death is controversial. Categorizing the death occurring after various heat loads as either apoptosis or necrosis might help to elucidate this problem, since it has been shown that these two processes differ in their mode of initiation as well as in their morphological and biochemical features. Log-phase cultures of mastocytoma P-815 x 2.1 were heated at temperatures ranging from 42 to 47 degrees C for 30 min. After 42 degrees C heating a slight increase in apoptosis was observed morphologically. However, after heating at 43, 43.5 and 44 degrees C, there was marked enhancement of apoptosis, and electrophoresis of DNA showed characteristic internucleosomal cleavage. With heating at 45 degrees C both apoptosis and necrosis were enhanced, whereas at 46 and 47 degrees C only necrosis was produced. DNA extracted from the 46 and 47 degrees C cultures showed virtually no degradation, which contrasts with the random DNA breakdown observed in necrosis produced by other types of injury; lysosomal enzymes released during heat-induced necrosis may be inactivated at the higher temperatures. It is suggested that apoptosis following heating may be triggered either by a limited increase in cytosolic calcium levels resulting from mild membrane changes or by DNA damage. Necrosis, on the other hand, is likely to be a consequence of severe membrane disruption.