Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats

Armağan, İlkay; Bayram, Dilek; Candan, İbrahim Aydın; Yiğit, Ayşe; Celik, Erdal; Armağan, Hamit Hakan; Uğuz, Abdülhadi Cihangir

doi:10.1016/j.etap.2015.04.003

Cited by 77 publications

(67 citation statements)

References 39 publications

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“…It has been reported that increased peroxynitrite caused renal injury and damage to arteries and tubules [39]. Previous studies showed that an MTX overdose led to nephrotoxicity due to lipid peroxidation, which resulted in increased levels of malondialdehyde (MDA), NO release, and ROS formation [2,5,6,[27][28][29][30]. Similarly, in the present study, the level of NO was increased in the kidney tissues of the MTX group.…”

Section: Discussionsupporting

confidence: 75%

“…However, some studies demonstrated that the main factor in MTX-associated tissue injury was oxidative damage, with subsequent free-radical generation [4][5][6]. The role of oxidative stress has been documented in MTX-induced nephrotoxicity [2,5,6,[27][28][29][30]38] and hepatotoxicity [6,29,30]. Here, we showed for the first time that HLX ameliorated MTX-induced oxidative stress and nephrotoxicity.…”

Section: Discussionmentioning

confidence: 53%

“…As a direct result, the side effects of chemotherapy and radiotherapy are reduced [24][25][26]. Several studies demonstrated that various agents, including caffeic acid phenethyl ester [5], melatonin [27], curcumin [28], thymoquinone [29], pentoxifylline [2,30], and alpha-lipoic acid [30], had beneficial effects helping to reduce MTX-induced tissue damage. Considering the nephrotoxic and genotoxic effects of MTX, we hypothesized that a V. album preparation (Helixor ® (HLX)) may improve MTX-induced oxidative stress and nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (Viscum album L.) Extract

et al. 2017

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Background: The protective effect of mistletoe extract (Helixor®, HLX) against methotrexate (MTX)-induced acute oxidative stress and nephrotoxicity in rats was evaluated by histological and biochemical methods as well as the comet assay. Material and Methods: 32 female Wistar albino rats were divided into 4 groups: control group, HLX group (5 mg/kg body weight (bw), days 1-10, intraperitoneally (i.p.)), MTX group (10 mg/kg bw, days 7, 8, and 9, i.p.), and MTX + HLX group (10 mg/kg bw, days 7, 8, and 9, i.p. + 5 mg/kg bw, days 1-10, i.p.). At the end of the experiment, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide (NO), and myeloperoxidase (MPO) levels were measured, and a histopathological analysis and comet assay were carried out. Results: MTX induced renal oxidative stress and nephrotoxicity in the rats. Pretreatment with HLX significantly improved the renal GSH-Px and SOD activities in the MTX + HLX group compared to the MTX group. The decrease in the NO and MPO levels in the rat groups pretreated with HLX was not significant. The histochemical evaluation revealed that HLX provided significant improvement in the MTX-induced renal degenerative changes, including tubule distension, interstitial inflammation, perirenal inflammation, glomerular congestion, glomerular degeneration, and parenchymal hemorrhage, in the MTX + HLX group compared to the MTX-administered group. According to the comet assay, pretreatment with HLX lowered the MTX-induced DNA damage in endogenous lymphocytes, although not significantly. Conclusion: This study demonstrated that HLX administration markedly reduced the MTX-induced acute oxidative stress and nephrotoxicity in rats through its antioxidant and anti-inflammatory properties.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

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Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (Viscum album L.) Extract

et al. 2017

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“…Hepatotoxicity and production of ROS are main side effects induced by MTX [9]. Then it has been advised to prevent MTX-induced hepatotoxicity, it is using concomitant with antioxidants [10]. Several protective agents such as penthoxyphyllin, alpha lipoic acid and beta carotenes have been investigated in different studies for prevention of MTX-caused hepatotoxicity [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Then it has been advised to prevent MTX-induced hepatotoxicity, it is using concomitant with antioxidants [10]. Several protective agents such as penthoxyphyllin, alpha lipoic acid and beta carotenes have been investigated in different studies for prevention of MTX-caused hepatotoxicity [10,11]. Vitamin E is considered a lipid soluble vitamin and an important antioxidant.…”

Section: Introductionmentioning

confidence: 99%

The use of 99mTc-phytate for assessment the protective effect of vitamin E against hepatotoxicity induced by methotrexat in rat

et al. 2018

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Hepatotoxicity is one of the most common side effects of methotrexate (MTX) therapy in patients. The aim of this study was to evaluate the protective effect of vitamin E against MTX-induced hepatotoxicity using 99m Tc-phytate as a radiopharmaceutical agent in animals. Rats were divided into five groups as follows: control, solvent, Vit E (100 mg/kg), MTX (20 mg/kg) and Vit E + MTX. Animals were intraperitoneally injected with Vit E for 17 days before MTX injection and continued for 4 days. Tc-phytate was injected into the tail of rats after the 21 days of Vit E administration. Percentage of the injected dose per gram of liver and spleen tissues (%ID/g) was calculated in treated rats. Liver imaging was obtained with gamma camera. In other experiment, liver of treated rats was assessed for histopathology. Tc-phytate uptake (%ID/g) of livers in control, solvent, Vit E, MTX and Vit E + MTX groups were 8.99% ± 1.37, 8.53% ± 2.91, 8.65% ± 3.84, 3.22% ± 1.09 and 8.38% ± 2.68. Vit E administration resulted in a significant increase of the level of %ID/g in MTX-injected animal. Vit E pre-treatment improved the shape of liver in MTX-treated rat which was seen abnormal view in planar imaging. Histophatological examinations approved the protective effect of Vit E against MTX-induced hepatotoxicity in rats. The results of this study show that Vit E significantly attenuates the MTX-induced hepatotoxicity in rats, and 99m Tc-phytate is an acceptable radiopharmaceutical agent for assessment of liver and spleen damages in the animal model.

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Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha‐lipoic acid on primary ovarian insufficiency

Kong,

Cho,

Hwang

et al. 2023

J of Cellular Biochemistry

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Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha‐lipoic acid (ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA‐related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis, protein–protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein‐to‐protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top 10 hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple targets and multiple pathways mechanisms.

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Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats

Cited by 77 publications

References 39 publications

Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (<b><i>Viscum album</i></b> L.) Extract

Methotrexate-Induced Nephrotoxicity in Rats: Protective Effect of Mistletoe (<b><i>Viscum album</i></b> L.) Extract

The use of 99mTc-phytate for assessment the protective effect of vitamin E against hepatotoxicity induced by methotrexat in rat

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha‐lipoic acid on primary ovarian insufficiency

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