Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats

Open Medicine ◽  
2009 ◽  
Vol 4 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Kerim Cayir ◽  
Ali Karadeniz ◽  
Abdulkadir Yildirim ◽  
Yildiray Kalkan ◽  
Akar Karakoc ◽  
...  

AbstractThe present study was designed to investigate the protective effects of L-carnitine (LC) on changes in the levels of lipid peroxidation and endogenous antioxidants induced by cisplatin (cis-diamminedichloroplatinum II, CDDP) in the liver and kidney tissues of rats. Twenty-four Sprague Dawley rats were equally divided into four groups of six rats each: control, cisplatin, L-carnitine, and L-carnitine plus cisplatin. The degree of protection produced by L-carnitine was evaluated by determining the level of malondialdehyde (MDA). The activity of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and superoxide dismutase (SOD) were estimated from liver and kidney homogenates, and the liver and kidney were histologically examined as well. L-carnitine elicited significant liver and kidney protective activity by decreasing the level of lipid peroxidation (MDA) and elevating the activity of GSH, GSHPx, GST, and SOD. Furthermore, these biochemical observations were supported by histological findings. In conclusion, the present study indicates a significant role for reactive oxygen species (ROS) and their relation to liver and kidney dysfunction, and points to the therapeutic potential of LC in CDDP-induced liver and kidney toxicity.

Author(s):  
MOHAMMAD IQBAL ◽  
MUHAMMAD DAWOOD SHAH ◽  
SENTY VUN-SANG ◽  
RIANA BINTI AWANG SAMAN

Objective: The pathogenesis of various liver injuries involves oxidative damage. This research was planned to examine the effects of Mereemia borneensis extract on hepatic oxidative damage caused by carbon tetrachloride (CCl4) in rats. Methods: Sprague Dawley rats were exposed to M. borneensis (125 and 250 mg/kg b. wt.) once daily for 14 d followed by two doses of CCl4 (1.2 ml/kg b. wt.). After 2 w, the rats were sacrificed and hepatoprotective analysis was done. Results: Orally administration of CCl4 enhances serum transaminase (ALT; alanine transaminase and AST; aspartate transaminase), γ-glutamyl transpeptidase, lipid peroxidation, reduction in glutathione, catalase, glutathione reductase, glutathione peroxidase, quinone reductase and glutathione S-transferase. Pretreatment of rats with M. borneensis at 125 and 250 mg/kg body weight significantly reduced levels of ALT, AST, γ-glutamyl transpeptidase and lipid peroxidation of CCl4 treated rats. Pretreatment with M. borneensis against rats treated with CCl4, hepatic enzymatic and non-enzymatic antioxidant molecules have increased significantly. A decreased histopathological change in the liver is further evidence of the protective effect of M. borneensis. Conclusion: Our data suggest that M. borneensis can be a potential hepatoprotective agent in preventing or treating degenerative diseases that involve oxidative stress.


1978 ◽  
Vol 175 (3) ◽  
pp. 937-943 ◽  
Author(s):  
Barbara F. Hales ◽  
Valerie Jaeger ◽  
Allen H. Neims

The glutathione S-transferases that were purified to homogeneity from liver cytosol have overlapping but distinct substrate specificities and different isoelectric points. This report explores the possibility of using preparative electrofocusing to compare the composition of the transferases in liver and kidney cytosol. Hepatic cytosol from adult male Sprague–Dawley rats was resolved by isoelectric focusing on Sephadex columns into five peaks of transferase activity, each with characteristic substrate specificity. The first four peaks of transferase activity (in order of decreasing basicity) are identified as transferases AA, B, A and C respectively, on the basis of substrate specificity, but the fifth peak (pI6.6) does not correspond to a previously described transferase. Isoelectric focusing of renal cytosol resolves only three major peaks of transferase activity, each with narrow substrate specificity. In the kidney, peak 1 (pI9.0) has most of the activity toward 1-chloro-2,4-dinitrobenzene, peak 2 (pI8.5) toward p-nitrobenzyl chloride, and peak 3 (pI7.0) toward trans-4-phenylbut-3-en-2-one. Renal transferase peak 1 (pI9.0) appears to correspond to transferase B on the basis of pI, substrate specificity and antigenicity. Kidney transferase peaks 2 (pI8.5) and 3 (pI7.0) do not correspond to previously described glutathione S-transferases, although kidney transferase peak 3 is similar to the transferase peak 5 from focused hepatic cytosol. Transferases A and C were not found in kidney cytosol, and transferase AA was detected in only one out of six replicates. Thus it is important to recognize the contribution of individual transferases to total transferase activity in that each transferase may be regulated independently.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Catherine Crinigan ◽  
Matthew Calhoun ◽  
Karen L. Sweazea

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.


2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.


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.


2012 ◽  
Vol 63 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Xiu-Quan Shi ◽  
Wei Yan ◽  
Ke-Yue Wang ◽  
Qi-Yuan Fan ◽  
Yan Zou

We tested the hypothesis that dietary fi bre (DF) has protective effects against manganese (Mn)-induced neurotoxicity. Forty-eight one-month old Sprague-Dawley rats were randomly divided into six groups: control, 16 % DF, Mn (50 mg kg-1 body weight), Mn+ 4 % DF, Mn+ 8 % DF, and Mn+ 16 % DF. After oral administration of Mn (as MnCl2) by intragastric tube during one month, we determined Mn concentrations in the blood, liver, cerebral cortex, and stool and tested neurobehavioral functions. Administration of Mn was associated with increased Mn concentration in the blood, liver, and cerebral cortex and increased Mn excretion in the stool. Aberrations in neurobehavioral performance included increases in escape latency and number of errors and decrease in step-down latency. Irrespective of the applied dose, the addition of DF in forage decreased tissue Mn concentrations and increased Mn excretion rate in the stool by 20 % to 35 %. All neurobehavioral aberrations were also improved. Our fi ndings show that oral exposure to Mn may cause neurobehavioral abnormalities in adult rats that could be effi ciently alleviated by concomitant supplementation of DF in animal feed.


2020 ◽  
Vol 23 (4) ◽  
pp. 570-579
Author(s):  
Mahboubeh Sheikhan ◽  
◽  
Mohammad Reza Kordi ◽  
Hamid Rajabi ◽  
◽  
...  

Background and Aim: Several microRNAs are involved in regulating muscle mass, which plays an essential role in hypertrophy and atrophy of skeletal muscle, The present study examined the expression of some genes as regulators of muscular atrophy following a period of inertia in rats. Methods & Materials: For this purpose, 18 male Sprague-Dawley rats were divided into three groups (Control, Exercise+inactivity, and Inactivity). The exercise+inactivity group run on the treadmill for 18 weeks and five times per week. The hindlimb of the animal was immobilized for seven days with the casting method. Soleus muscle was extracted and the expression of the genes was measured by the RT-PCR method. Univariate ANOVA and Tukey post hoc test was used to determine the differences (α=0.05). Ethical Considerations: The Ethics Committee of the Tehran University of Medical Sciences Research approved this study (Code: IR.SUMS.REC.1396.S 463). Results: Results showed that immobilization in both Exercise+ inactivity and inactivity groups, compare to the control group, increased expression of miR-1 genes (P<0.10), FOXO3a (P<0.001) and decreased expression of miR-206 (P<0.007) and IGF-1 (P<0.001). This difference was statistically significant. Conclusion: According to the results of this study, it can be said that changes in the expression of RNAs by chromatography cause changes in the expression of muscle regulating genes, and although endurance exercises have protective effects, they cannot prevent these changes.


2020 ◽  
Vol 12 (4) ◽  
pp. 298
Author(s):  
Dana N. Abdelrahim ◽  
Hamed R. Takruri ◽  
Khalid M. Al-Ismail

This study aimed to determine the effect of Ruta chalepensis L. plant on liver enzymes, liver weight and lipid peroxidation using rats toxified with paracetamol. An animal experiment was conducted using five groups of Sprague Dawley rats, 9 rats each. The groups were fed: Normal diet, high cholesterol diet, with or without the plant or the liver toxicant paracetamol (PCM). The experiment lasted six weeks; at the end of the sixth week; a single dose of 3 g paracetamol/kg body weight was given for rats of two groups, then blood and liver samples were collected. The hepatoprotective effect of the plant was evaluated using aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBL) levels as indicators. This study finds that the groups to which plant and PCM were given had significantly lower MDA levels in comparison with other groups that didn&rsquo;t receive plant before PCM toxification. Tested liver enzymes levels were significantly (P &lt; 0.05) lowered by the introduction of plant to the diet. Introducing PCM without ingestion of plant in the diet significantly (P &lt; 0.05) increased the rats absolute liver weight. It is concluded that the use of Ruta chalepensis L. plant significantly lowered hepatic toxicity as indicated by the liver enzymes levels. Also, the plant lowered the MDA level and liver weight. The ingestion of the plant can be significantly protective against hepatic injury.


2020 ◽  
Vol 39 (11) ◽  
pp. 1565-1581
Author(s):  
S Iqbal ◽  
F Jabeen ◽  
C Peng ◽  
MU Ijaz ◽  
AS Chaudhry

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia ( C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably ( p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.


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