The Concept of Activity Profiles of Antimutagens

Waters, Michael D.; Brady, Ann L.; Stack, H.Frank; Brockman, Herman E.

doi:10.1007/978-1-4615-9561-8_7

Cited by 5 publications

(6 citation statements)

References 51 publications

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“…Each animal was assessed for 1,000 polychromatic erythrocytes (PCEs) to estimate MNPCE frequency. The PCE:NCE ratio was measured by scoring 1,000 erythrocytes per animal to assess cytotoxicity (Waters et al, 1990).…”

Section: In Vivo Bone Marrow Micronuclei Assaysmentioning

confidence: 99%

Amelioration of cyclophosphamide-induced DNA damage, oxidative stress, and hepato- and neurotoxicity by Piper longum extract in rats: The role of γH2AX and 8-OHdG

et al. 2023

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Background: The identification of genoprotectants is a promising strategy for improving human health. Piper longum has drawn scientific attention because of its diverse biological effects and traditional utilization. The current investigation aims to evaluate the genome-stabilizing potential of Piper longum against cyclophosphamide-associated genotoxicity.Methods: We adopted a funnel screening with a three-tier evaluation approach, where Piper longum was investigated in an acellular medium, peripheral blood lymphocytes, and a rodent model. The genoprotective action of the Piper longum extract was initially performed with plasmid pBluescript SK(-) DNA. Furthermore, the extract and various fractions were screened against cyclophosphamide-induced genotoxicity using a cytokinesis-block micronucleus assay and a chromosomal aberration assay in human peripheral blood lymphocytes. The genome-stabilizing action of the extract and potent (hexane) fraction was further confirmed in vivo in Wistar albino rats by evaluating them using mammalian erythrocyte micronucleus tests, DNA fragmentation, oxidative stress markers, 8-hydroxy-2-deoxyguanosine (8-OHdG), γH2AX, and histopathological lesions in the liver and hippocampus. Additionally, acute and sub-acute toxicity studies were conducted following the Organization for Economic Co-operation and Development (OECD) guidelines for rats. Furthermore, the extract was quantified and characterized by high-performance thin-layer chromatography (HPTLC), ultra-high performance liquid chromatography–mass spectroscopy (UPLC-MS), and gas chromatography–mass spectrometry (GC-MS).Results: The Piper longum ethanol extract was shown to protect plasmid pBluescript SK(-) DNA against H2O2-induced strand breaks. In human lymphocytes, the extract and hexane fraction showed a reduction in micronucleus formation (p < 0.001) and chromosomal aberrations (p < 0.01) against cyclophosphamide. Furthermore, the extract and fraction treatment, when administered at 200 mg/kg for 28 days in Wistar rats, restored cyclophosphamide-induced genomic instability by reducing micronucleus formation and DNA fragmentation; restoring redox homeostasis; decreasing 8-OHdG, a hallmark of oxidative DNA damage; reducing γH2AX, a DNA double-strand break (DSB) marker; and preserving the liver and hippocampus against histopathological lesions. The extract and fraction revealed no signs of systemic toxicity at the used doses. Piperine and piperlongumine are the major alkaloids quantified along with the presence of flavonoids in the ethanol extract and the presence of fatty acids and terpenoids in the hexane fraction of Piper longum.Conclusion: Our investigation confirms the genoprotective action of Piper longum by reducing cyclophosphamide-associated cytogenotoxicity, oxidative stress, hepato- and neurotoxicity, oxidative DNA damage, and DNA double-strand breaks. The outcomes are critical for mitigating the genotoxic effects of chemotherapy recipients, requiring further attention.

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Section: In Vivo Bone Marrow Micronuclei Assaysmentioning

confidence: 99%

Amelioration of cyclophosphamide-induced DNA damage, oxidative stress, and hepato- and neurotoxicity by Piper longum extract in rats: The role of γH2AX and 8-OHdG

et al. 2023

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“…Em contraste, algumas plantas contém substâncias inibidoras que interferem nas etapas dos eventos mutagênicos, apresentando efeitos moduladores da mutagênese (Waters et al 1990). Embora evidências diretas sobre a origem mutacional das doenças somáticas humanas sejam limitadas, inferências obtidas a partir de resultados experimentais em vários organismos fornecem apoio consistente para a visão de que muitas doenças têm suas raízes nas mutações.…”

Section: 1unclassified

“…A incidência de doenças genéticas pode ser reduzida pelo decréscimo nas taxas de mutação, uma das estratégias para a proteção das populações humanas seria, portanto, a identificação dos agentes mutagênicos, seguida da implementação de medidas de controle do risco genético, através da diminuição da exposição humana a estes agentes (De Flora, 1998). Assim, surge uma nova possibilidade para a proteção da saúde humana, que é a identificação e caracterização de substâncias naturais ou sintéticas que são capazes de modular os efeitos da mutagênese e são ditas antimutagênicas (Waters et al 1990;Hartaman e Shankel, 1990). Estudos relatam que substâncias extraídas de frutas, vegetais e plantas contém compostos como os polifenóis, dentre outros, que apresentam um efeito protetor do organismo contra doenças (Kaur et al 2015).…”

Section: 1unclassified

“…La utilización de plantas desconocidas desde el punto de vista toxicológico, puede causar eventos mutacionales somáticos o germinativos, desencadenando enfermedades o desordenes hereditarios multiples en los seres humanos (Corrêa et al 1999). En contraste, algunas plantas contienen substancias inibidoras que interfieren en diferentes etapas de los eventos mutagénicos, presentando efectos moduladores de la mutagénesis (Waters et al 1990).…”

Section: Introductionunclassified

“…Una de las estrategias para la protección de las poblaciones humanas sería, por tanto, la identificación de los agentes mutagénicos, seguida por la implementación de medidas del control de riesgo genético, a través de la disminuición de la exposición humana a estos agentes (De Flora, 1998). Así surge una nueva posibilidad para la protección de la salud humana, y es la identificación y caracterización de substancias naturales o sinteticas que sean capaces de modular los efectos de la mutagenesis y que son llamadas de antimutagénicas (Waters et al 1990;Hartman & Shankel, 1990 Estudios relatan que substancias extraídas de frutas, vegetales y plantas contienen compuestos como los polifenoles, entre otros, que presentan un efecto protector del organismo contra enfermedades (Kaur et al, 2015).…”

Section: Introductionunclassified

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