Protective effect of N-acetylcysteine on cyclophosphamide-induced cardiotoxicity in rats

Mansour, Heba H.; kiki, Shereen M. El; Hasan, Hesham Farouk

doi:10.1016/j.etap.2015.07.013

Cited by 57 publications

(48 citation statements)

References 42 publications

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“…The known effects of CP, such as hepatotoxicity, nephrotoxicity, cardiotoxicity, oncogenic potential of secondary neoplasias, and generation of oxygen reactive species, are dependent on the administration dose and time of exposure (Mansour et al 2015;Fahmy et al 2016). In this study, CP had no significant effect on the studied parameters, which was also observed by Basu et al (2015viz., oxovanadium(IV).…”

Section: Resultssupporting

confidence: 85%

First phytochemical and biological study of the ethanolic extract from leaves of Capirona decorticans (Rubiaceae)

et al. 2018

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Capirona decorticans (Rubiaceae) is popularly used to treat warts, wounds, mycoses and scabies, and is also a component of the Ayahuasca tea. Despite its popular use, the phytochemical and pharmacological research on this species is limited. Therefore, this work quantified phenolic compounds in the ethanolic extract (EE) and hydromethanolic fraction (FM) (406, 293 mgEAG g-1, respectively) from leaves of C. decorticans. We identified flavonoids by LC-MS/MS-MMR-ESI (apigenin, rutin, luteolin, miricetin, quercetin, quercetin-3-β-D-glucoside, quercetrin), and evaluated oxidative stress and mutagenic/antimutagenic effect of EE and FM through an in vivo experiment using Swiss mice and cyclophosphamide (CP) as an inducer of DNA damage and oxidative stress. Mice were pretreated for 15 consecutive days with EE or FM (250 mg kg-1) and then intraperitoneally injected with CP (25 mg kg-1). Carbonylated proteins, ascorbic acid, catalase and thiobarbituric acid-reactive substances were measured in hepatic and renal tissues. The mutagenic/antimutagenic effect was evaluated through the Micronucleus Test. Protein carbonylation in the liver of animals exposed to CP was reduced by FM. There was no significant effect on other markers of oxidative stress. The groups treated with the extracts showed a significant percentage reduction (EE = 96% and FM = 71%) in the frequency of micronucleated polychromatic erythrocytes induced by CP. EE showed mutagenicity when used alone. The EE and FM of C. decorticans leaves showed antioxidant potential equivalent to that observed in other species, did not cause oxidative stress, nor toxicity, and had a protective and antimutagenic effect, although the EE showed signs of mutagenicity.

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Section: Resultssupporting

confidence: 85%

First phytochemical and biological study of the ethanolic extract from leaves of Capirona decorticans (Rubiaceae)

et al. 2018

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“…While LPO was increased, the SOD, CAT and GPx activities were diminished in the testicular and epididymal cells after CP treatment. It is known that these detoxification enzymes, such as SOD and GPx, are important cellular defence mechanisms against oxidative damage caused by free radicals (Mansour, El Kiki, & Hasan, ) and are involved in severe testicular damage (He et al., ). While the CP changed the antioxidant endogenous system, the co‐treatment with A. aculeata oil increased the activity of these enzymes, in a similar way to that observed following treatment with BC.…”

Section: Discussionmentioning

confidence: 99%

Acrocomia aculeataoil: Beneficial effects on cyclophosphamide-induced reproductive toxicity in male rats

et al. 2018

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This study aimed to evaluate the effects of the extracted oil of Acrocomia aculeata pulp in preventing or mitigating the reproductive toxicity induced by cyclophosphamide (CP) in male rats. Adult male rats were segregated into seven groups that received vehicle, 100 mg/kg/day of CP, or 10 mg/kg/day of β-carotene or 3 or 30 mg/kg/day of A. aculeata oil co-administered with CP. A. aculeata oil exhibited a high content of β-carotene. CP treatment induced reproductive toxicity in the animals, as it changed the reproductive organs weight, hormone levels, sperm counts and testicular histology. In contrast, co-administration of A. aculeata improved CP-induced alterations in these parameters. A. aculeata oil also increased the gene Ckit expression and normalised the antioxidant enzymes levels which were changed by CP. The A. aculeata oil is capable of protecting the male reproductive system from the adverse effects of CP, possibly by acting as an antioxidant and increasing the Ckit gene expression.

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“…2015; Mansour et al, 2015). Adduction of these electrophiles can prevent or reduce subsequent development of cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Enolate-Forming Phloretin Pharmacophores: Hepatoprotection in an Experimental Model of Drug-Induced Toxicity

Geohagen

Vydyanathan

Kosharskyy

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Drug-induced toxicity is often mediated by electrophilic metabolites, such as bioactivation of acetaminophen (APAP) to N-acetylp-benzoquinone imine (NAPQI). We have shown that APAP hepatotoxicity can be prevented by 2-acetylcyclopentanone (2-ACP). This 1,3-dicarbonyl compound ionizes to form an enolate nucleophile that scavenges NAPQI and other electrophilic intermediates. In this study, we expanded our investigation of enolate-forming compounds to include analyses of the phloretin pharmacophores, 29,49,69-trihydroxyacetophenone (THA) and phloroglucinol (PG). Studies in a mouse model of APAP overdose showed that THA provided hepatoprotection when given either by intraperitoneal injection or oral administration, whereas PG was hepatoprotective only when given intraperitoneally. Corroborative research characterized the molecular pharmacology (efficacy, potency) of 2-ACP, THA, and PG in APAP-exposed isolated mouse hepatocytes. For comparative purposes, N-acetylcysteine (NAC) cytoprotection was also evaluated. Measurements of multiple cell parameters (e.g., cell viability, mitochondrial membrane depolarization) indicated that THA and, to a lesser extent, PG provided concentration-dependent protection against APAP toxicity, which exceeded that of 2-ACP or NAC. The enolateforming compounds and NAC truncated ongoing APAP exposure and thereby returned intoxicated hepatocytes toward normal viability. The superior ability of THA to protect is related to multifaceted modes of action that include metal ion chelation, free radical trapping, and scavenging of NAPQI and other soft electrophiles involved in oxidative stress. The rank order of potency for the tested cytoprotectants was consistent with that determined in a parallel mouse model. These data suggest that THA or a derivative might be useful in treating drug-induced toxicities and other conditions that involve electrophile-mediated pathogenesis.

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Protective effect of N-acetylcysteine on cyclophosphamide-induced cardiotoxicity in rats

Cited by 57 publications

References 42 publications

First phytochemical and biological study of the ethanolic extract from leaves of Capirona decorticans (Rubiaceae)

First phytochemical and biological study of the ethanolic extract from leaves of Capirona decorticans (Rubiaceae)

Acrocomia aculeataoil: Beneficial effects on cyclophosphamide-induced reproductive toxicity in male rats

Enolate-Forming Phloretin Pharmacophores: Hepatoprotection in an Experimental Model of Drug-Induced Toxicity

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