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.

Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review.

Oxidative stress is considered to be the main cause of diabetic complications. As the role of antioxidants in diabetes therapy is still underestimated, the aim of the present investigation was to study the antioxidative action of melatonin in comparison with N-acetylcysteine (NAC) under diabetic conditions. Alloxan-diabetic rabbits were treated daily with either melatonin (1 mg/kg, i.p.), NAC (10 mg/kg, i.p.) or saline. Blood glutathione redox state and serum hydroxyl free radicals (HFR), creatinine and urea levels were monitored. After 3 wk of treatment animals were killed and HFR content, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio as well as the activities of glutathione reductase, glutathione peroxidase and gamma-glutamylcysteine synthetase were estimated in both liver and kidney cortex. Diabetes evoked a several-fold increase in HFR levels accompanied by a significant decline in GSH/GSSG ratio in serum and the examined organs. In contrast to NAC, melatonin (at 1/10 the dose of NAC) attenuated diabetes-induced alterations in glutathione redox state and HFR levels, normalized creatinine concentration and diminished urea content in serum. Moreover, the indole resulted in an increase in glutathione reductase activity in both studied organs and in a rise in glutathione peroxidase and gamma-glutamylcysteine synthetase activities in the liver. In contrast to NAC, melatonin seems to be beneficial for diabetes therapy because of its potent antioxidative and nephroprotective action. The indole-induced increase in the activities of the enzymes of glutathione metabolism might be of importance for antioxidative action of melatonin under diabetic conditions.

Melatonin attenuates diabetes-induced oxidative stress in rabbits.

http://scimfac.mans.edu.eg/arabic/authorguide/zoology.pdf/Prof.%20Thanaa%20A.%20A.%20Fayed.Physiology.pdf

Ameliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injury

Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine–Tryptophan–Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39–71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity.

Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation.

Protective effect of rutin on the ischemia/reperfusion induced damage in rat kidney.

Melatonin ameliorates renal ischemia/reperfusion injury.

Antecedentes:
No hay suficiente evidencia sobre la frecuencia de re
-
chazo agudo y la funcion del injerto en los pacientes con retiro tem
-
prano de esteroides (RTE). El objetivo del presente estudio es comparar
el efecto del RTE sobre la tasa de filtrado glomerular (TFG), la super
-
vivencia/rechazo del injerto en receptores de una cohorte de tratados
con tacrolimus/mofetil micofenolato, comparada con un grupo con
-
trol.
Material y metodos:
Cohorte retrospectiva en 60 receptores de
bajo riesgo inmunologico entre diciembre de 2005 y julio de 2010.
Cohorte del estudio (C-RTE; N
=
32), el RTE se hizo el 5o dia mientras
recibian tacrolimus/mofetil micofenolato. La cohorte control (C-C, N =
28) recibio prednisona/tacrolimus/mofetil micofenolato. Las variables
clinicas, bioquimicas e histologicas fueron evaluadas al inicio del estu
-
dio, y a los 3, 6 y 12 meses de seguimiento. Se utilizo Kaplan-Meier y el
modelo de riesgos proporcionales de Cox para evaluar la superviven
-
cia. Las comparaciones entre cohortes fueron hechas por la
t
de Stu
-
dent y
c
2
.
Resultados:
Durante el seguimiento, la C-C muestra presion
sanguinea significativamente mayor tanto sistolica (125
±
10 frente a
114
±
8) como diastolica (81
±
8 frente a 72
±
7), glucosa serica (96
±
13
frente a 86
±
10), trigliceridos (177
±
61 frente a 129
±
34), colesterol
total (183
±
43 frente a 148
±
34) y colesterol LDL (100
±
22 frente a
87
±
25). La C-C presento una mayor proporcion de uso de antihiper
-
tensivos (57 frente a 13
%) y de estatinas (27 frente a 9
%). La tasa
de filtrado glomerular estimada (TFGe) fue mejor en la C-RTE que en
la C-C (85,4
±
20,6 frente a 70,6
±
17,0,
p
=
0,004
). La frecuencia de
rechazo agudo fue menor en la C-RTE.
Conclusiones:
La superviven
-
cia del injerto, la TFG, la tasa de rechazo agudo y el perfil metabolico
fueron mejores en la C-RTE que en la C-C

/pdf/retiro-temprano-de-esteroides-en-una-cohorte-de-trasplante-21kc3iyegr.pdf

Retiro temprano de esteroides en una cohorte de trasplante renal tratada con tacrolimus, mofetil micofenolato y basiliximab

Background: The B-cell activating factor (BAFF) controls the maturation and survival of B cells. An imbalance in this cytokine has been associated with systemic autoimmunity in SLE and lupus nephritis (LN). However, few investigations have evaluated the tissular expression of BAFF in LN. This study aimed to associate BAFF system expression at the tissular level with the proliferative LN classes. Methods: The analysis included eighteen kidney tissues, with sixteen LN (class III = 5, class IV = 6, class III/IV+V = 4, and class V = 1), and two controls. The tissular expression was evaluated with an immunochemistry assay. A Cytation5 imaging reader and ImageJ software were used to analyze the quantitative expression. A p-value < 0.05 was considered significant. Results: The expressions of BAFF, A proliferation-inducing ligand (APRIL), and their receptors were observed in glomerular, tubular, and interstitial zones, with BAFF being the most strongly expressed in the overall analysis. BAFF-Receptor (BR3), transmembrane activator and CALM interactor (TACI), and B-Cell maturation antigen (BCMA) displayed higher expressions in LN class IV in all zones analyzed (p < 0.05). Additionally, a positive correlation was found between APRIL, TACI, and BCMA at the glomerular level; BCMA and APRIL in the interstitial zone; and BR3, TACI, and BCMA in the tubule (p < 0.05). Conclusions: The expression of BAFF and BAFF receptors is mainly associated with LN class IV, emphasizing the participation of these receptors as an essential pathogenic factor in kidney involvement in SLE patients.

https://www.mdpi.com/2077-0383/12/1/71/pdf?version=1671689689

Francisco Ramos-Solano

Papers

Melatonin ameliorates renal ischemia/reperfusion injury.

Retiro temprano de esteroides en una cohorte de trasplante renal tratada con tacrolimus, mofetil micofenolato y basiliximab

Renal Tissue Expression of BAFF and BAFF Receptors Is Associated with Proliferative Lupus Nephritis