Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues.

/pdf/cell-biology-of-ischemia-reperfusion-injury-1rdtb8k8os.pdf

Cell Biology of Ischemia/Reperfusion Injury

The incidence rate of AKI in hospitalized patients is increasing. However, relatively little attention has been paid to the association of AKI with long-term risk of adverse coronary events. Our study investigated hospitalized patients who recovered from de novo dialysis-requiring AKI between 1999 and 2008 using patient data collected from inpatient claims from Taiwan National Health Insurance. We used Cox regression with time-varying covariates to adjust for subsequent CKD and ESRD after discharge. Results were further validated by analysis of a prospectively constructed database. Among 17,106 acute dialysis patients who were discharged, 4869 patients recovered from dialysis-requiring AKI (AKI recovery group) and were matched with 4869 patients without AKI (non-AKI group). The incidence rates of coronary events were 19.8 and 10.3 per 1000 person-years in the AKI recovery and non-AKI groups, respectively. AKI recovery associated with higher risk of coronary events (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.36 to 2.04) and all-cause mortality (HR, 1.67; 95% CI, 1.57 to 1.79) independent of the effects of subsequent progression to CKD and ESRD. The risk levels of de novo coronary events after hospital discharge were similar in patients with diabetes alone and patients with AKI alone (P=0.23). Our results reveal that AKI with recovery associated with higher long-term risks of coronary events and death in this cohort, suggesting that AKI may identify patients with high risk of future coronary events. Enhanced postdischarge follow-up of renal function of patients who have recovered from temporary dialysis may be warranted.

Long-Term Risk of Coronary Events after AKI

http://if-pan.krakow.pl/pjp/pdf/2012/1_31.pdf

Animal models of acute renal failure

Hyperlipidemia Enhanced Oxidative Stress and Inflammatory Response Evoked by Renal Ischemia/Reperfusion Injury

It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

https://www.tandfonline.com/doi/pdf/10.3109/0886022X.2010.504911

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Background: Elevation of serum homocysteine is considered to contribute to endothelial dysfunc- tion, which is considered to be the initial event in vascular disease following renal transplantation. We sought to investigate whether an association exist- ed between serum homocysteine levels and endo- thelial dysfunction after renal ischemia/reperfusion (I/R) injury. Materials and methods: Acetylcholine (Ach)-induced endothelium-dependent and sodium nitroprusside (SNP)-induced endothelial-independent relaxation responses were determined in thoracic aortas from different I/R groups. A correlation analysis was per- formed between Ach responses and homocysteine levels. Results: Long-term I/R injury decreased the respons- es to acetylcholine and the pD 2 values of the con- centration response curves compared with controls. While vascular responses to SNP were unchanged among all groups. Homocysteine levels correlated with the pD 2 values of acetylcholine among control and I/R groups, indicating that the increase in homo- cysteine was associated with decreased sensitivity to acetylcholine. In short-term I/R rats, no associa- tion was observed between these parameters. Conclusion: These data suggest a possible link be- tween serum homocysteine and decreased vascular reactivity to endothelium-dependent relaxation in I/R aorta.

http://www.sin-italy.org/web/eventi/SIN/archivio/jn/2011/jnephrol_2011_5/631-635%20BHALODIA.pdf

Homocysteine-dependent endothelial dysfunction induced by renal ischemia/reperfusion injury.

Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.) and identification of the active ingredient.

https://www.jyoungpharm.org/sites/default/files/10.4103_0975-1483.51883.pdf

N. P. Jivani

Papers

Hyperlipidemia Enhanced Oxidative Stress and Inflammatory Response Evoked by Renal Ischemia/Reperfusion Injury

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Homocysteine-dependent endothelial dysfunction induced by renal ischemia/reperfusion injury.

Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.) and identification of the active ingredient.

Protective Effect of Polyherbal Formulation on Simvastatin Hepatotoxicity in Rats