Ischemic acute kidney injury may be exacerbated by an inflammatory response. How injury elicits inflammation remains a major question in understanding acute kidney injury. The present review examines the hypothesis that molecules released by injured cells elicit inflammation.
After necrotic death, intracellular molecules find their way into the extracellular space. These molecules include heat shock proteins and HMGB1. Receptors for these proteins include TLR4, TLR2, CD91 and RAGE. These proinflammatory mechanisms may be so useful that nature has evolved mechanisms for programming necrotic death via poly(ADP-ribose) polymerase and cyclophilin D. In addition, apoptosis may also elicit inflammation.
The concepts discussed in this review are important for clinical medicine. Drugs and genetic manipulation may ameliorate ischemic kidney injury by regulating the inflammatory response to cell injury.
"Acute kidney injury (AKI), previously known as acute tubular necrosis (ATN), is characterized by abrupt and reversible kidney dysfunction, caused by sepsis, ischemia or nephrotoxic agents. The major underlying pathogenic mechanisms are apoptosis and necrosis of kidney tubular cells , in particular in the proximal convoluted tubuli. Many recent studies suggest that chaperones, in particular members of the Hsp70 family, may provide protection against AKI  (for recent reviews see , , ). "
[Show abstract][Hide abstract] ABSTRACT: Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses.
PLoS ONE 02/2008; 3(8):e2998. DOI:10.1371/journal.pone.0002998 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have been studying the occurrence of low velocity detonations (LVI) in several liquid explosives. A hypothesis based on shock wave interactions and Mach reflections was proposed to explain the initiation and propagation of LVD. Using the card gap test we found general experimental agreement with this hypothesis. However, certain anomalous effects were noted. In addition, we developed a method to study the internal wave structure of a shocked liquid. This technique was applied to a liquid that sustains LVD and to one that does not. A comparison of these liquids shows that the reaction zone in a liquid explosive undergoing LVD is consistent with the Mach zone hypothesis.
The anomalous effects noted during gap testing were subjected to a photographic study using a high speed framing camera. The results of this study showed that mechanisms other than that explainable by the Mach zone hypothesis were also responsible for LVD initiation. These were wave reflections from witness plates for high sound speed-high strength confinement and donor air shock initiation for lead (low sound speed-low strength) confinement. We conclude that there appears to be no unique mechanism for LVD and that each mechanism proposed so far explains some of the observations.
Symposium (International) on Combustion 01/1969; 12(1):731–742. DOI:10.1016/S0082-0784(69)80454-6
[Show abstract][Hide abstract] ABSTRACT: Renal ischemia-reperfusion (I-R) contributes to the development of ischemic acute renal failure (ARF). Multi-factorial processes are involved in the development and progression of renal I-R injury with the generation of reactive oxygen species, nitric oxide and peroxynitrite, and the decline of antioxidant protection playing major roles, leading to dysfunction, injury, and death of the cells of the kidney. Renal inflammation, involving cytokine/adhesion molecule cascades with recruitment, activation, and diapedesis of circulating leukocytes is also implicated. Clinically, renal I-R occurs in a variety of medical and surgical settings and is responsible for the development of acute tubular necrosis (a characteristic feature of ischemic ARF), e.g., in renal transplantation where I-R of the kidney directly influences graft and patient survival. The cellular mechanisms involved in the development of renal I-R injury have been targeted by several pharmacological interventions. However, although showing promise in experimental models of renal I-R injury and ischemic ARF, they have not proved successful in the clinical setting (e.g., atrial natriuretic peptide, low-dose dopamine). This review highlights recent pharmacological developments, which have shown particular promise against experimental renal I-R injury and ischemic ARF, including novel antioxidants and antioxidant enzyme mimetics, nitric oxide and nitric oxide synthase inhibitors, erythropoietin, peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP-ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine. Novel approaches such as recent research involving combination therapies and the potential of non-pharmacological strategies are also considered.
Archiv für Experimentelle Pathologie und Pharmakologie 11/2007; 376(1-2):1-43. DOI:10.1007/s00210-007-0183-5 · 2.47 Impact Factor
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