scholarly journals Study of the Potential Use of Lithium in Treatment of Acute Kidney Injury in Rat Model

2018 ◽  
Vol 6 (2) ◽  
pp. 14-19
Author(s):  
Mahmoud Abdelaziz Kora ◽  
Yassin Salah Yassin ◽  
Ahmed Mohamed Zahran ◽  
Ahmed Ragheb ◽  
Safwa Othman Abdellatif ◽  
...  

 Background: Management of acute kidney injury is still facing a big problem. It is only dependent up till now on supportive measures, like fluid resuscitation and renal replacement therapy. No current drug therapy has been approved for the treatment of acute kidney injury. Acute kidney injury situations in a lot of cases can be predicted so, finding a drug for AKI will really benefit many patients. The pathophysiology of AKI is complex and many signaling pathways are involved in it. The Glycogen synthase kinase 3B enzyme is an important member in some of these pathways. The effect of its inhibition by the FDA approved drug, lithium on AKI is still under study.Material & Methods: The current study was conducted on28 Male Sprague–Dawley rats. We classified the rats into groups. We induced acute kidney injury to rats with cisplatin. We administered lithium chloride to treat AKI in comparison with saline treatment. We have done renal functions and histopathological examinations to all rats enrolled in our study.Results: Single intraperitoneal injection of cisplatin (5 mg/kg) in rat induced acute kidney injury. The effect of lithium chloride treatment with dose (80 mg/kg) on serum creatinine and blood urea levels showed significant regression in the rising of serum creatinine and blood urea in lithium chloride treated rats in comparison to saline-treated rats. Pathological pictures and scores demonstrated an improvement in lithium chloride treated rats than saline-treated but results were not significant.Conclusion:Administration of lithium may be a promising treatment for acute kidney injury.Journal of Nobel Medical CollegeVolume 6, Number 2, Issue 11 (July-December, 2017) Page:14-19

2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Rehab H. Ashour ◽  
Mohamed-Ahdy Saad ◽  
Mohamed-Ahmed Sobh ◽  
Fatma Al-Husseiny ◽  
Mohamed Abouelkheir ◽  
...  

Author(s):  
HAYDER M AL-KURAISHY ◽  
ALI I AL-GAREEB ◽  
HUDA ABDULBAKI RASHEED

Objectives: Nephrotoxicity is a renal-specific situation in which the excretion of toxic metabolites is reduced due to toxic agents and drugs. Gentamicin is an antibiotic belongs to aminoglycoside group which may induce nephrotoxicity due to induction of oxidative stress. Curcumin is a component of traditional medicine with significant nephroprotective effect. Therefore, the objective of the present study was to evaluate the nephroprotective effect of curcumin on gentamicin-induced nephrotoxicity. Methods: A total of 30 male Sprague-Dawley rats were used which divided into Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus gentamicin 100 mg/kg for 12 days, and Group 3 (n=10): Rats treated with curcumin 100 mg/kg plus gentamicin 100 mg/kg for 12 days. Blood urea, serum creatinine, malondialdehyde (MDA), kidney injury molecule (KIM-1), and cystatin-C were measured in both control and experimental groups. Results: Rats treated with gentamicin showed nephrotoxicity as evident by significant elevation in blood urea, serum creatinine, KIM-1, MDA, and cystatin-C sera levels. Curcumin leads to significant reduction of blood urea and serum creatinine compared to gentamicin group, p<0.05. Curcumin also reduced MDA, KIM-1, and cystatin-C sera levels significantly compared to gentamicin group, p<0.01. Conclusion: Curcumin produced significant nephroprotective effect on gentamicin-induced nephrotoxicity through modulation of oxidative stress and inflammatory biomarkers.


2019 ◽  
Vol 51 (8) ◽  
pp. 2838-2841
Author(s):  
Won Seo Park ◽  
Min Su Park ◽  
Sang Wook Kang ◽  
Seul A. Jin ◽  
Youngchul Jeon ◽  
...  

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhiquan Zhang ◽  
Qing Ma ◽  
Mihai V Podgoreanu

Introduction: Acute kidney injury (AKI) is a prevalent and prognostically important complication of cardiac surgery. The complex multifactorial pathogenesis and lack of appropriate animal models to recapitulate the clinical insults leading to CSA-AKI have been implicated in the failure of multiple pharmacologic renoprotective strategies. We have reported anti-inflammatory and renoprotective effects of a novel Annexin-A1 (ANXA1) tripeptide (Ac-QAW) in a rodent model of experimental cardiac surgery. Here, we tested the hypothesis that Ac-QAW attenuates CSA-AKI by upregulating Sirtuin6 and Forkhead box protein O3 (SIRT6/FoxO3), key players in stress resistance, cell survival, and life span. Methods: Male Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA). Animals were treated (iv) with 1 mg/kg Ac-QAW (n = 6), the commercially available ANXA1 peptide Ac2-26 (as a positive control; n = 5), or vehicle (n = 6) at 1 h before CPB, during CA, and 1 h after CPB. At 24 h post-reperfusion, renal levels of activated caspase-3, ANXA1, SIRT6, and FoxO3 were determined by Western blot; renal and plasma levels of myeloperoxidase (MPO) were determined by ELISA. Results: At 24 hours post-reperfusion following CPB/CA, rats treated with Ac-QAW showed a) reduced renal caspase-3 activity (P < 0.05); b) decreased MPO in both blood and kidney; and c) increased renal levels of ANXA1 (P < 0.05), SIRT6, and FoxO3 (P < 0.01) (Figure). Conclusions: Using a clinically relevant animal model, we provide preliminary translatable evidence that administration of Ac-QAW attenuates CSA-AKI. This may result from action by Ac-QAW to 1) reduce inflammation by increasing inflammation-resolving molecule ANXA1; 2) inhibit neutrophil transmigration; and 3) promote pro-survival mechanisms by increasing SIRT6/FoxO3 expression. More Ac-QAW studies are needed to define its exact mechanism of action and its impact on long-term functional outcomes.


2018 ◽  
Vol 81 (11) ◽  
pp. 397-407 ◽  
Author(s):  
Ji Su Kim ◽  
Ji Yeon Son ◽  
Kyeong Seok Kim ◽  
Hyun Jung Lim ◽  
Mee-Young Ahn ◽  
...  

2016 ◽  
Vol 9 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Fatma E Moustafa ◽  
Mohamed-A Sobh ◽  
Mohamed Abouelkheir ◽  
Youmna Khater ◽  
Khalid Mahmoud ◽  
...  

2019 ◽  
Vol 23 (2) ◽  
pp. 43 ◽  
Author(s):  
O. A. Grebenchikov ◽  
A. V. Lobanov ◽  
E. R. Shayhutdinova ◽  
A. N. Kuzovlev ◽  
A. V. Ershov ◽  
...  

<p><strong>Aim.</strong> To investigate the cardioprotective effect of lithium chloride in vivo on a rat model of myocardial infarction.<br /><strong>Methods.</strong> Twelve male Sprague-Dawley rats were randomly divided into two groups of six, with both groups modelling cardiac ischaemia and subsequent reperfusion. At the start of reperfusion, 30 mg/kg of 4.2% lithium chloride solution was intravenously administered via a catheter to the test group and 0.5 ml/kg of saline solution was administered to the comparison group. A control group comprised sham-operated rats that were not injected with any drugs other than anaesthesia during making skin incision. At the end of each experiment, the total area of the risk zone and areas of the infarction zone and left ventricle were calculated for each animal using a double-staining technique with 2% methylene blue and 1% triphenyltetrazolium chloride. A further series of experiments using 15 male Sprague-Dawley rats (third group) was performed to assess the protein content of glycogen synthase-3β in myocardial tissue. The method was similar to that for the earlier experiments; however, at the end of the experiments, the hearts were removed and homogenised, following which the concentration of glycogen synthase-3β was determined using electrophoresis.<br /><strong>Results.</strong> The group treated with lithium chloride showed a significant decrease in the area of the infarction zone compared with the group treated with saline. The difference in the indices between the two groups was &gt;26% (p &lt; 0.05).<br /><strong>Conclusion.</strong> This study demonstrated that 30 mg/kg of 4.2% lithium chloride solution, administered at the onset of reperfusion, exerted a protective effect on cardiomyocytes in a rat model of myocardial infarction by reducing the area of the infarction zone compared with that in the control group. This effect was probably mediated by an almost two-fold increase in the content of the phosphorylated form of glycogen synthase-3β in the myocardium.</p><p>Received 23 June 2019. Revised 6 August 2019. Accepted 7 August 2019.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p><p><strong>Author contributions</strong> <br />Conception and study design: A.N. Kuzovlev<br />Data collection and analysis: O.A. Grebenchikov<br />Statistical analysis: A.V. Ershov<br />Drafting the article: A.V. Lobanov, E.R. Shayhutdinova<br />Critical revision of the article: V.V. Likhvantsev<br />All authors approved final version to be published.<br /><br /></p>


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