On the Performance of Trimetazidine and Vitamin E as Pharmacoprotection Agents in Cyclosporin A-Induced Toxicity

Cristina, De la Cruz Rodríguez Lilia; Rey, Rosario; Rosa, Araujo Carmen; Veronica, Oldano Ana

doi:10.1155/2013/605640

Cited by 4 publications

(1 citation statement)

References 22 publications

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“…Naringin, as an antioxidant, has previously been shown to improve antioxidant gene expression and antioxidant enzyme activity at the dose it was administered in the present study [ 41 , 53 , 54 ]. On the other hand, vitamin E has previously been administered at various doses for its ability to prevent lipid peroxidation in various tissues [ 31 , 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

Adebiyi

Owira

2015

Nutrients

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Nucleoside Reverse Transcriptase Inhibitors (NRTIs) have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7) were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT) (groups I, II III), 50 mg/kg stavudine (d4T) (groups IV, V, VI) and 3 mL/kg of distilled water (group VII). Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

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Section: Discussionmentioning

confidence: 99%

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

Adebiyi

Owira

2015

Nutrients

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Ameliorative effect of trimetazidine on cisplatin-induced hepatotoxicity in rats

Ateyya

Yosef

Nader

2016

Can. J. Physiol. Pharmacol.

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This study was designed to evaluate the protective effects of trimetazidine (TMZ) against cisplatin (CP) induced liver damage in rats. Animals were distributed among 4 groups as follows: control group; TMZ group (20 mg/kg body mass, per oral), which was treated for 10 days; CP group (6 mg/kg, by intraperitoneal injection), which received a single injection; and the CP + TMZ group (20 mg/kg, per oral), which received TMZ 4 days before and 6 days after CP injection. The extent of hepatic damage was studied by assessing biochemical parameters and histopathological evaluation of the extracted liver tissue. The results revealed that liver enzymes were markedly elevated after injection of CP, as evident from significant increases in the serum levels of alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GT), and lactate dehydrogenase (LDH), as well as marked changes to the liver architecture, with a significant decrease in serum levels of albumin. There were also marked changes to the antioxidant defense system, as indicated by significant decreases in total antioxidants and hepatic levels of reduced glutathione (GSH) and superoxide dismutase (SOD), together with a significant increase in lipid peroxidation. However, there was a significant increase in the activity of hepatic nuclear factor kappa B (NF-κB) as well as hepatic Bax protein expression. We conclude that TMZ protects against CP-induced liver damage through scavenging free radicals and anti-inflammatory and antiapoptotic effects, as well as through reducing NF-κB activation.

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The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats

El-Sherbeeny

Attia

2016

Can. J. Physiol. Pharmacol.

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Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into 4 groups; control Group, TMZ Group, CSP Group, and CSP + TMZ Group. CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis and inflammatory cell infiltrates; all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde levels (MDA), renal NF-κB (nuclear factor-kappa B) DNA-binding activity and protein expression, tumor necrosis factor-alpha (TNF-α) and IL-6 levels.Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6, NFκB expression and its DNA-binding activity caused by CSP administration.TMZ has protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress, and attenuation of CSP-induced inflammation.Keywords: Cisplatin, Oxidative stress, Trimetazidine, nephrotoxicity, NF-κB IntroductionTMZ, a piperazine derivative, is the first of a new class of metabolic agents. It has been found to have a cytoprotective effect on both renal and hepatic cells (Cristina et al. 2013). TMZ is well known for its cardioprotective effect and is used as adjuvant anti-anginal drug. It can normalize metabolic disturbances in low-flow myocardial ischemia and prevents the secondary cell death that may follow (Kantor et al. 2000; Sellier and Broustet 2003). TMZ acts by preserving intracellular levels of ATP through shifting cardiac metabolism from fatty acid oxidation to more glucose oxidation (Kantor et al. 2000). The drug may also reduce free-radical-mediated injury (Kaur et al. 2003), inhibit cell apoptosis (Khan et al. 2010) and improve endothelial function (Park et al. 2010).Cis-Diammineplatinum (II) dichloride (CSP) is the prototype of the platinum containing anti-cancer drugs. It's widely used in clinical practice as part of the standard treatment plans for various solid tumors (Oh et al. 2014). CSP adverse effects include ototoxicity, bone marrow suppression and hepatotoxicity but the main dose- The current study was undertaken to investigate the possible protective role of TMZ against CSP-induced renal damage in rats and to elucidate the possible underlying mechanism. Materials and methods MaterialsCisplatin (Bristol-Myers-Squibb Co.) was obtained as the pharmaceutical drug (5 mg/mL vial) and was diluted with isotonic saline. Trimetazidine dihydrochloride; Experimental protocolTwenty four rats were divided randomly into four groups with six rats for each group. received TMZ (20 mg/kg/day, p.o.) for ten consecutive days, Group III: received drug vehicle ...

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On the Performance of Trimetazidine and Vitamin E as Pharmacoprotection Agents in Cyclosporin A-Induced Toxicity

Cited by 4 publications

References 22 publications

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

Ameliorative effect of trimetazidine on cisplatin-induced hepatotoxicity in rats

The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats

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