Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats

Souza, Pablo Cambeses; Santos, Emanuel Burck dos; Motta, Giordana de Cássia Pinheiro da; Bona, Silvia Regina; Schaefer, Pedro Guilherme; Campagnol, Daniela; Bortolini, Tiago; Corso, Carlos Otávio

doi:10.1590/s0102-865020180030000001

Cited by 3 publications

(6 citation statements)

References 28 publications

(26 reference statements)

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“…It is thought that the protective results observed in animals receiving quercetin were a consequence of the reduced oxidative damage in renal tissue. However, oxidative stress has not been directly evaluated in the present study, as in others (27), and future studies should clarify the mechanisms of action. The use of this flavonoid was effective in preventing glomerular loss (N[glom]), which occurred only in animals subjected to renal ischemia without quercetin treatment.…”

Section: Discussionmentioning

confidence: 78%

Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model

et al. 2021

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Purpose: To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia. Materials and Methods: Male rats were allocated into 4 groups: sham (S), sham quercetin (SQ), ischemia (I), and ischemia quercetin (IQ). Groups SQ and IQ received quercetin (50mg/kg) before and after surgery. Groups I and IQ had their left renal vessels clamped for 60 minutes. All animals were euthanized four weeks after the procedure, and serum urea and creatinine levels were measured. Renal weight and volume, cortex-non-cortex area ratio (C-NC), cortical volume (CV), glomerular volumetric density (Vv[glom]), volume-weighted glomerular volume (VWGV) and number of glomeruli per kidney (N[glom]) were evaluated by stereological methods. Results were considered statistically signifi cant when p <0.05. Results: Serum urea levels in group I increased by 10.4% in relation to group S, but no differences were observed among the other groups. The C-NC of group I was lower than those of all other groups, and group IQ had similar results to sham groups. The Vv [glom] and N[glom] of group I were lower than those of group S (33.7% and 28.3%, respectively) and group IQ had no signifi cant difference compared to the S group. Conclusions: Quercetin was effective as a nephroprotective agent in preventing the glomerular loss observed when the kidney was subjected to warm ischemia. This suggests that this fl avonoid may be used preventively in kidney surgery, when warm ischemia is necessary, such as partial nephrectomy.

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Section: Discussionmentioning

confidence: 78%

Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model

et al. 2021

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“…Two hundred seventeen publications were identified after search. After removing duplicates and performing title and abstract screening, 35 papers were selected for full-text screening, and 31 met the inclusion criteria (Sener et al, 2002 ; Kunduzova et al, 2003 ; Sahna et al, 2003 ; Rodríguez-Reynoso et al, 2004 ; Aktoz et al, 2007 ; Kurcer et al, 2007a , b ; Fadillioglu et al, 2008 ; Ersoz et al, 2009 ; Sinanoglu et al, 2012 ; Ahmadiasl et al, 2013 , 2014a , b ; Sezgin et al, 2013 ; Cetin et al, 2014 ; Sehajpal et al, 2014 ; Hadj Ayed Tka et al, 2015 ; Oguz et al, 2015 ; Yilmaz et al, 2015 ; Yip et al, 2015 ; Banaei et al, 2016a , b ; Chang et al, 2016 ; Souza et al, 2018 ; Chen et al, 2019a , b ; Shi et al, 2019 ; M El Agaty and Ibrahim Ahmed, 2020 ; Wang et al, 2020 ; Yang et al, 2020 ; Zahran et al, 2020 ). Of the four publications excluded at the full-text level, two did not conduct renal I/R injury to AKI (Li et al, 2009 ; Zhu et al, 2017 ), and the other two used melatonin combined with other treatments (mesenchymal stem cell-derived exosomes, or nitric oxide synthase inhibitor) (Deniz et al, 2006 ; Alzahrani, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Most studies took melatonin intraperitoneal injection, except one with subcutaneous injection (Sener et al, 2002 ), one with intravenous injection (Kunduzova et al, 2003 ), and another one with oral administration (M El Agaty and Ibrahim Ahmed, 2020 ). Single-dose administration was conducted in 18 studies (Sener et al, 2002 ; Kunduzova et al, 2003 ; Sahna et al, 2003 ; Rodríguez-Reynoso et al, 2004 ; Kurcer et al, 2007a ; Ersoz et al, 2009 ; Ahmadiasl et al, 2013 , 2014a , b ; Cetin et al, 2014 ; Sehajpal et al, 2014 ; Hadj Ayed Tka et al, 2015 ; Oguz et al, 2015 ; Banaei et al, 2016a , b ; Souza et al, 2018 ; Wang et al, 2020 ; Zahran et al, 2020 ), while the others used multiple-dose administration (Deniz et al, 2006 ; Aktoz et al, 2007 ; Kurcer et al, 2007b ; Fadillioglu et al, 2008 ; Sinanoglu et al, 2012 ; Sezgin et al, 2013 ; Yilmaz et al, 2015 ; Yip et al, 2015 ; Chang et al, 2016 ; Chen et al, 2019a , b ; Shi et al, 2019 ; Yang et al, 2020 ). Two independent reviewers assessed the data, with a Kw of 0.817.…”

Section: Resultsmentioning

confidence: 99%

“…All of them were peer reviewed publication, and applied appropriate animal model, and anesthetic without significant intrinsic vascular protection activity, but none of them reported sample size calculation, and only 10 studies did not report control of temperature (Sener et al, 2002 ; Kunduzova et al, 2003 ; Sinanoglu et al, 2012 ; Sehajpal et al, 2014 ; Yilmaz et al, 2015 ; Chen et al, 2019b ; M El Agaty and Ibrahim Ahmed, 2020 ; Wang et al, 2020 ; Yang et al, 2020 ; Zahran et al, 2020 ). Randomization was conducted in 14 studies (Aktoz et al, 2007 ; Kurcer et al, 2007b ; Fadillioglu et al, 2008 ; Ersoz et al, 2009 ; Sinanoglu et al, 2012 ; Sezgin et al, 2013 ; Yilmaz et al, 2015 ; Yip et al, 2015 ; Souza et al, 2018 ; Chen et al, 2019a , b ; Shi et al, 2019 ; M El Agaty and Ibrahim Ahmed, 2020 ; Yang et al, 2020 ), then no study reported blinded induction of model, and blinded assessment of the outcome was applied in 15 studies (Sahna et al, 2003 ; Ersoz et al, 2009 ; Sinanoglu et al, 2012 ; Ahmadiasl et al, 2013 , 2014a , b ; Cetin et al, 2014 ; Yilmaz et al, 2015 ; Yip et al, 2015 ; Banaei et al, 2016a ; Chang et al, 2016 ; Souza et al, 2018 ; Shi et al, 2019 ; Yang et al, 2020 ). Most of the studies reported compliance with animal welfare regulations (Sahna et al, 2003 ; Wang et al, 2020 ), while 10 studies reported potential conflicts of interest and study funding (Sener et al, 2002 ; Rodríguez-Reynoso et al, 2004 ; Aktoz et al, 2007 ; Ersoz et al, 2009 ; Ahmadiasl et al, 2013 ; Sehajpal et al, 2014 ; Yilmaz et al, 2015 ; Yip et al, 2015 ; Banaei et al, 2016a , …”

Section: Resultsmentioning

confidence: 99%

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Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

et al. 2022

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Background: Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury.Objectives: This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models.Methods and Results: The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = −30.00 [−42.09 to −17.91], p < 0.00001), and serum creatinine (SCr) (20 studies, WMD = −0.91 [−1.17 to −0.66], p < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease.Conclusions: From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.

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“…In our present study, renal glomerular and tubular lesions and histopathological scores in Group III were significantly reduced following 4 h- and 6 h-HT one day following ROSC compared with Group II. Ribeiro et al ( 46 ) and Souza et al ( 50 ) reported that HT was effective in animal models of renal I/R injury. Islam et al ( 23 ) and Jawad et al ( 22 ) determined that HT reduced the severity of renal injury and increased the survival rate in an asphyxial CA model.…”

Section: Discussionmentioning

confidence: 99%

Effect of therapeutic hypothermia against renal injury in a rat model of asphyxial cardiac arrest: Α focus on the survival rate, pathophysiology and antioxidant enzymes

et al. 2021

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Although multi-organ dysfunction is associated with the survival rate following cardiac arrest (CA), the majority of studies to date have focused on hearts and brains, and few studies have considered renal failure. The objective of the present study, therefore, was to examine the effects of therapeutic hypothermia on the survival rate, pathophysiology and antioxidant enzymes in rat kidneys following asphyxial CA. Rats were sacrificed one day following CA. The survival rate, which was estimated using Kaplan-Meier analysis, was 42.9% one day following CA. However, hypothermia, which was induced following CA, significantly increased the survival rate (71.4%). In normothermia rats with CA, the serum blood urea nitrogen level was significantly increased one day post-CA. In addition, the serum creatinine level was significantly increased one day post-CA. However, in CA rats exposed to hypothermia, the levels of urea nitrogen and creatinine significantly decreased following CA. Histochemical staining revealed a significant temporal increase in renal injury after the normothermia group was subjected to CA. However, renal injury was significantly decreased in the hypothermia group. Immunohistochemical analysis of the kidney revealed a significant decrease in antioxidant enzymes (copper-zinc superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase and catalase) with time in the normothermia group. However, in the hypothermia group, these enzymes were significantly elevated following CA. Collectively, the results revealed that renal dysfunction following asphyxial CA was strongly associated with the early survival rate and therapeutic hypothermia reduced renal injury via effective antioxidant mechanisms.

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Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats

Cited by 3 publications

References 28 publications

Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model

Quercetin as a nephroprotector after warm ischemia: histomorphometric evaluation in a rodent model

Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

Effect of therapeutic hypothermia against renal injury in a rat model of asphyxial cardiac arrest: Α focus on the survival rate, pathophysiology and antioxidant enzymes

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