L-Carnitine Ameliorates Glycerol-Induced Myoglobinuric Acute Renal Failure in Rats

Üstündağ, Sedat; Sen, Sayan; Yalçın, Ömer; Ciftci, Senturk; Demirkan, Bora; Türe, Mevlüt

doi:10.1080/08860220802599130

Cited by 33 publications

(22 citation statements)

References 37 publications

(59 reference statements)

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“…Unfortunately, some patients still progress to AKI. 19 Oxidative stress, inflammation, and renal tubular epithelial cell necrosis play important roles in rhabdomyolysis-induced AKI, and the application of L-carnitine, carvedilol, 20,21 and hepatocyte growth factor 22,23 can attenuate rhabdomyolysis-induced AKI. However, these agents are not yet used clinically.…”

Section: Discussionmentioning

confidence: 99%

Fasudil Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of Apoptosis

et al. 2011

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During times of war or natural disasters, rhabdomyolysis leading to acute kidney injury (AKI) can assume epidemic proportions. Fasudil attenuates ischemia/reperfusion-induced AKI. We investigated the therapeutic effect of an early application of fasudil on AKI induced by rhabdomyolysis and explored the potential mechanisms. Male Wistar rats were randomly divided into a control group (saline, 7 mL/kg, i.m.), a Gly group (50% glycerol, 7 mL/kg, i.m.), and a fasudil group (50% glycerol, 7 mL/kg, i.m.; fasudil, 20 mg/kg bodyweight, i.p., three times every 24 h beginning 72 h before glycerol administration). Serum creatinine, blood urea nitrogen (BUN), and histopathological changes were used to demonstrate kidney function 24 h after the glycerol injection. Cell apoptosis and the expression of rho-associated protein kinase member (ROCK1), phosphatase and tensin homolog (PTEN), P-Akt, and caspase-8, -9, and -3 were measured. Serum creatinine and BUN levels increased significantly in Gly group compared with control group. Both levels decreased after fasudil treatment. The renal tubular damage score was significantly lower and cell apoptosis was significantly less in fasudil group compared with Gly group. The expression levels of ROCK1, PTEN, and caspase-8, -9, and -3 were upregulated significantly in Gly group, and their expression was reduced in the fasudil group. The P-Akt level was decreased in Gly group and upregulated significantly in fasudil group. Early application of fasudil reduced rhabdomyolysis-associated renal injury by inhibiting Rho kinase and thereby activating the PI-3K/Akt pathway, which decreased cell apoptosis via both the intrinsic and extrinsic apoptotic pathways.

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Section: Discussionmentioning

confidence: 99%

Fasudil Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of Apoptosis

et al. 2011

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“…7 Group 2 (n ¼ 6) were intramuscularly injected with 50% glycerol (10 mL/kg) in each hind leg. Group 3 (n ¼ 6) were intramuscularly injected with 50% glycerol (10 mL/kg) in each hind leg and orally received dexamethasone (0.1 mg/kg) starting at the same time as the glycerol injections.…”

Section: Experimental Designmentioning

confidence: 99%

“…5,6 And there is growing evidence indicating that the reactive oxygen species (ROS) plays an important role in the pathogenesis of myoglobinuric ARF, oxidative stress would participate in the tubular necrosis favoring lipid peroxidation of cellular membranes. 1,[7][8][9] In the kidney, NO is an important molecule in the regulation of renal microvascular tone, and much evidence suggests that intrarenal oxygen supply is NO, inappropriate high release of NO related to the tubular injury, inhibition of the renal endothelial NO synthase (eNOS), therefore the main production of NO is iNOS, an enzyme which can be blocked by dexamethasone. 10,11 Dexamethasone is glucocorticosteroid which have been advocated for decades, and it can inhibit the production of iNOS by attenuation in gene expression.…”

Section: Introductionmentioning

confidence: 99%

L-Citrulline Protects Against Glycerol-Induced Acute Renal Failure in Rats

Liu

Gou

et al. 2013

Renal Failure

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There is an increasing evidence that oxidative stress plays an important role in the pathogenesis of rhabdomyolysisinduced acute renal failure (ARF). In this study, protective effects of L-citrulline on glycerol-induced ARF in rats were investigated. Six groups of rats were employed in this study: group 1 served as a control; group 2 was only given glycerol (50%, 10 mL/kg, i.m.); group 3 was given glycerol plus dexamethasone (0.1 mg/kg, i.g.) as positive reference drug, starting at the same time as the glycerol injections; the last three groups were given glycerol plus L-citrulline (300, 600, and 900 mg/kg, i.g.) respectively, starting at the same time as the glycerol injections. The injections of glycerol were only once, and after glycerol injections the i.g. administrations of dexamethasone and L-citrulline were repeated every 24 h for 7 days. After 7 days of glycerol injections, the blood samples and kidney tissues were harvested for future biochemical and pathology analyses. The levels of creatinine (Cr) and urea nitrogen (BUN) in plasma, the content of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), the activity of total nitric oxide synthase (TNOS), inducible nitric oxide synthase (iNOS), endothelial NO synthase (eNOS), and superoxide dismutase (SOD) were evaluated in kidney tissues. Consequently, administrations of L-citrulline improved an impaired intrarenal oxygenation and kidney function compared with the glycerol group, and prevented the renal oxidative stress damage as well as severe functional and morphological renal deterioration. Therefore, L-citrulline might have potential application in the amelioration of glycerol-induced ARF.

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“…LC reversed the increases in blood BUN and creatinine following the doxorubicin or gentamicin caused renal injuries. LC has been shown to reduce the severity of glycerol-induced myoglobinuric kidney damages, indicating that LC may be a beneficial agent in the prevention and treatment of glycerol-induced myoglobinuric acute renal failure (Ustundag et al, 2009). The mechanisms of the renal protective effect of LC are not entirely clear.…”

Section: Discussionmentioning

confidence: 97%

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

Cao

Chen

Wang

et al. 2013

Braz. J. Pharm. Sci.

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The urine excretion of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-Lcarnitine (PLC) and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD), total antioxidative capacity (T-AOC), malondialdehyde (MDA) and nitrogen monoxidum (NO) activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 μmol, 166.93±76.87 μmol, 219.92±76.30 μmol, 100.48±23.89 μmol, 72.07±25.77 μmol, respectively. The excretion of ALC was 29.70±14.43 μmol, 80.59±32.70 μmol, 109.85±49.21 μmol, 58.65±18.55 μmol, and 80.43±35.44 μmol, respectively. The urine concentration of PLC was 6.63±4.50 μmol, 15.33±12.59 μmol, 15.46±6.26 μmol, 13.41±11.66 μmol and 9.67±7.92 μmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277) or T-AOC (r = 0.9547), and a negative correlation was found between urine LC excretions and NO (r = -0.8575) or MDA (r = 0.7085). In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.Uniterms: L-carnitine/antioxidant activity. Acetyl-L-carnitine/antioxidant activity. Propionyl-Lcarnitine/ antioxidant activity. Antioxidants. Urine excretion/analysis. A excreção urinária de L-carnitina (LC), acetil-L-carnitina (ALC) e propionil-L-carnitine (PLC) e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g) foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. INTRODUCTIONL-carnitine (3-hydroxy-4-N-trimethylammonium butyrate, LC) is an endogenous compound which has several physiological functions. LC is involved in the transfer of long-chain fatty acids across the inner matrix membrane of mitochondria (Mancinelli et al., 2007). It also regulates acetyl storage and transfer in mitochondria, cells, and between organs, and the transport of potentially toxic, activated acids out of mitochondria (Bellinghieri et al., 2003). LC is believed to be important for acting as an osmo protectant in organs such as the kidney, and as a general cell membrane stabilizer (Lahjouji et al., 2004;Biolo et al., 2008). LC homeostasis is maintained by a modest biosynthesis in the liver and kidney, absorption from dietary sources (eg, meat and dairy products), and efficient renal tubular reabsorption from glomerular filtrate (Rebouche, Seim 1998). Short-chain carnitine esters, including acetylLcarnitine (ALC) and propionyl-L-carni...

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L-Carnitine Ameliorates Glycerol-Induced Myoglobinuric Acute Renal Failure in Rats

Cited by 33 publications

References 37 publications

Fasudil Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of Apoptosis

Fasudil Ameliorates Rhabdomyolysis-Induced Acute Kidney Injury via Inhibition of Apoptosis

L-Citrulline Protects Against Glycerol-Induced Acute Renal Failure in Rats

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

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