Attenuation of Ischemia-Reperfusion Injury in a Canine Model of Autologous Renal Transplantation

Lin, Angello; Sekhon, Charanpal; Sekhon, Bipanjeet; Smith, Allyson; Chavin, Kenneth D.; Orak, John K.; Singh, Inderjit; Singh, Avtar

doi:10.1097/01.tp.0000131664.18670.17

Cited by 37 publications

(34 citation statements)

References 23 publications

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“…With this model of canine autologous kidney transplant, renal function decreased, confirmed by an elevation in serum creatinine values and comparable to previous results with this model (16,17). As expected, the accompanying decrease in renal plasma clearance of iodinated contrast medium could be detected by CT. Serum creatinine is an insensitive indirect measurement of renal function, increasing only when GFR is severely impaired (22).…”

Section: Discussionsupporting

confidence: 89%

Patlak plot analysis CT‐GFR for the determination of renal function: comparison of normal dogs with autologous kidney transplant dogs

Alexander

Authier

Castillo

et al. 2010

Contrast Media & Molecular

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Glomerular filtration rate (GFR) can be determined using Patlak plot analysis with single-slice dynamic computed tomography (CT). Acute autologous graft failure has several causes, all of which induce a measurable decrease in glomerular filtration rate. This study demonstrated in an experimental model of canine autologous renal transplant that CT-derived renal plasma clearance was significantly lower (p = 0.002) in dogs having undergone transplant (0.077 +/- 0.058 ml min(-1) ml renal tissue(-1)) compared with control dogs (0.396 +/- 0.139 ml min(-1) ml renal tissue(-1)). A significant negative curvilinear relationship was seen between serum creatinine and total renal plasma clearance (R(2) = 0.84, p = 0.0001). Alterations in renal time attenuation curve shape in dogs having undergone transplant may have been related to increased renal vascular resistance related to tubular necrosis. CT-GFR may be a useful experimental tool in the evaluation of renal dysfunction in transplant models.

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Section: Discussionsupporting

confidence: 89%

Patlak plot analysis CT‐GFR for the determination of renal function: comparison of normal dogs with autologous kidney transplant dogs

Alexander

Authier

Castillo

et al. 2010

Contrast Media & Molecular

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“…22 AICAR-induced activation of AMPK is reported to inhibit the NF-B-dependent expression of adhesion molecules (ICAM-1 and VCAM-1) in human umbilical vein endothelial cells. 45 Likewise, anti-inflammatory properties of AICAR protects against injury during cardiac ischemia and reperfusion in transplanted rat heart 46 and dog kidney 47 as well as in chest trauma and inflamed tissues. 48,49 Recently, we documented the restoration of the remyelination process in the CNS of lovastatin-treated EAE animals via enhanced survival and differentiation of oligodendrocyte progenitors, 21 but its effect on the survival and differentiation of neuronal axons in vivo deserve detailed investigation.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effect of Combination Therapy with Lovastatin and 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Alleviates Neurodegeneration in Experimental Autoimmune Encephalomyelitis

Paintlia

Singh

et al. 2006

The American Journal of Pathology

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Combination therapy with multiple sclerosis (MS) therapeutics is gaining momentum over monotherapy for improving MS. Lovastatin, an HMG-CoA reductase inhibitor (statin), was immunomodulatory in an experimental autoimmune encephalomyelitis (EAE) model of MS. Lovastatin biases the immune response from Th1 to a protective Th2 response in EAE by a different mechanism than 5-aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside, an immunomodulating agent that activates AMP-activated protein kinase. Here we tested these agents in combination in an EAE model of MS. Suboptimal doses of these drugs in combination were additive in efficacy against the induction of EAE; clinical symptoms were delayed and severity and duration of disease was reduced. In the central nervous system, the cellular infiltration and proinflammatory immune response was decreased while the anti-inflammatory immune response was increased. Combination treatment biased the class of elicited myelin basic protein antibodies from IgG2a to IgG1 and IgG2b, suggesting a shift from Th1 to Th2 response. In addition, combination therapy lessened inflammation-associated neurodegeneration in the central nervous system of EAE animals. These effects were absent in EAE animals treated with either drug alone at the same dose. Thus, our data sug- Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS) that mimics many aspects of multiple sclerosis (MS). 1Pathophysiology of EAE includes breaching of the blood brain barrier, infiltration of mononuclear cells-predominantly myelin-reactive CD4 ϩ and CD8 ϩ T-cells and macrophages, resulting in the activation of resident CNS glial cells.2 Different from EAE, however, myelin-reactive CD8 ϩ T cells play a major role in MS pathogenesis.3 On activation CNS glial cells secrete proinflammatory mediators [cytokines, chemokines, and inducible nitric oxide (NO) synthase] and activate complement cascade pathways. 4 These events produce excitotoxic and oxidative damage because of the depletion of intracellular energy stores, destabilization of the cell membrane, opening of voltage-gated Ca 2ϩ channels, and activation of NMDA receptors in neurons and oligodendrocytes. [5][6][7] Moreover, depletion of ATP in astrocytes during EAE leads to mitochondrial malfunction and cellular energy failure, contributing to neuron loss. 8,9 Consequently, these inflammatory events lead to CNS demyelination because of degradation of the myelin sheath and a loss of both oligodendrocytes and neuronal axons in the CNS.

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“…CD, collecting duct; DT, distal tubule; mTAL, medullary thick ascending limb; PT, proximal tubule. (4,135,163) and cultured human PTCs (332), its use for the treatment of patients with CKD has been disappointing (186,252). However, in patients with end-stage renal disease, NAC did reduce inflammatory cytokines (119,198) while improving early outcomes in kidney transplant recipients (54).…”

Section: N-acetylcysteinementioning

confidence: 99%

Oxidant Mechanisms in Renal Injury and Disease

Ratliff

Abdulmahdi

Pawar

et al. 2016

Antioxidants & Redox Signaling

512

513

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Significance: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/ disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. Recent Advances: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/ RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. Critical Issues: The review summarizes the critical sources of oxidative stress in the kidney during injury/ disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules. Future Directions: Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones.

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Attenuation of Ischemia-Reperfusion Injury in a Canine Model of Autologous Renal Transplantation

Abstract: Combination therapy with AICAR and NAC attenuates renal I/R injury and improves the outcome of the transplanted kidney after prolonged cold preservation.

Cited by 37 publications

References 23 publications

Patlak plot analysis CT‐GFR for the determination of renal function: comparison of normal dogs with autologous kidney transplant dogs

Patlak plot analysis CT‐GFR for the determination of renal function: comparison of normal dogs with autologous kidney transplant dogs

Immunomodulatory Effect of Combination Therapy with Lovastatin and 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Alleviates Neurodegeneration in Experimental Autoimmune Encephalomyelitis

Oxidant Mechanisms in Renal Injury and Disease

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