Modulatory role of rutin on 2,5-hexanedione-induced chromosomal and DNA damage in rats: validation of computational predictions

Abstract

The aim of this study was to evaluate the potentials of rutin on 2,5-hexanedione-induced toxicities. Two successive phases were involved using in silico and in vivo approaches. The in silico was adopted for potential oral toxicity and docking. The in vivo was carried-out in two stages for two weeks; the ameliorative (stage 1, first week), preventive, and curative studies (stage 2, extended to second week). In stage 1, rats were divided into four groups of seven each (distilled water, 3% (v/v) 2,5-hexanedione, 10 mg/kg rutin, and co-administration). In stage 2, the experimental groups were given either rutin or 2,5-hexanedione and treated in reverse order. Lipid peroxidation, protein carbonyl, and DNA fragmentation in tissues and bone marrow cells micronucleus were determined. The predicted Median lethal dose (LD) of >5000 mg/kg and toxicity class of five (5) indicates the safety of rutin when orally administered. 2,5-Hexanedione comfortably docked in to the active sites of SOD (-22.857Kcal/mol; KI = 0.9621 µM), GPx (-11.2032Kcal/mol; KI = 0.9813 µM), and CAT (-16.446Kcal/mol; KI = 0.9726 µM) with strong hydrogen bond and hydrophobic interactions. However, only strong hydrophobic interaction was observed in the case of DNA (-3.3296Kcal/mol; KI = 0.9944). In vivo findings revealed deleterious effects of 2,5-hexanedione through induction of oxidative and chromosomal/DNA damage characterized by higher level of malondialdehyde, micronuclei formations, and DNA fragmentation. These have invariably, validates the findings from in silico experiments. Furthermore, rutin was able to ameliorate, protect, and reverse these effects, and was relatively non-toxic corroborating toxicity predictions. Rutin exhibited counteractive effects on 2,5-hexanedione-induced oxidative, chromosomal, and DNA damage.

Sickling-preventive effects of rutin is associated with modulation of deoxygenated haemoglobin, 2,3-bisphosphoglycerate mutase, redox status and alteration of functional chemistry in sickle erythrocytes

“…Changes in the functional chemistry may as well be connected with membrane stabilizing effects of rutin currently observed bearing in mind that, erythrocytes akin to other cells composed of lipids, proteins and carbohydrates at membranous and non-membranous levels. Rutin has also been reported to have high bioavailability that enhances its antioxidant properties as currently observed based on the decreased in lipid peroxidation and increased in GSH, CAT and SOD (Muhammad et al., 2018). Equally, treatment with rutin has been reportedly associated with anti-inflammatory and protein stability effects which may be beneficial in battling SCD associated oxidative stress, inflammation and decreased haemoglobin S stability (Nafees et al., 2015).…”

“…Arguably, the sickling process in SCD patients is characterized by unceasing polymerization of erythrocytes due to oxidative stress in addition to insufficient oxygen supply distinctive of sickle erythrocytes (Erukainure et al., 2017; Imaga, 2013; Poillon et al., 1995). The antioxidant properties of rutin can help defend against oxidative stress that further enhances the stability of erythrocyte membranes (Muhammad et al., 2018, 2015; Nafees et al., 2015). This come to an agreement with previous studies which showed that treatment with rutin frustrated oxidative stress levels in treated experiments relative to non-treated controls (Muhammad et al., 2018).…”

“…The antioxidant properties of rutin can help defend against oxidative stress that further enhances the stability of erythrocyte membranes (Muhammad et al., 2018, 2015; Nafees et al., 2015). This come to an agreement with previous studies which showed that treatment with rutin frustrated oxidative stress levels in treated experiments relative to non-treated controls (Muhammad et al., 2018). Changes in the functional chemistry may as well be connected with membrane stabilizing effects of rutin currently observed bearing in mind that, erythrocytes akin to other cells composed of lipids, proteins and carbohydrates at membranous and non-membranous levels.…”

“…It is a low molecular weight polyphenolic compound that has been studied for its antioxidant properties in relation to human health and disease prevention (Cristina Marcarini et al., 2011; Yang et al., 2008). Recently, from our laboratory we reported the antioxidant, anticlastogenic and DNA-protective effects of rutin at in vitro and in vivo levels (Muhammad et al., 2018, 2015). It has also been shown to be protective against ROS-induced oxidative stress and inflammation (Nafees et al., 2015) which are conditions implicated in SCD.…”

Antisickling Effects of Quercetin may be Associated with Modulation of Deoxyhaemoglobin, 2, 3-bisphosphoglycerate mutase, Redox Homeostasis and Alteration of Functional Chemistry in Human Sickle Erythrocytes.

“…The proteins groundwork and energy minimization were done with the aid of Discovery studio 2.5v. The CHARMm-based DOCKER program was used to score the interaction between the proteins and the ligand (quercetin) into the crystal structure of the receptors binding compartments Muhammad et al, 2018). The PDB files of the best docked conformation were generated using Accerlrys discovery studio and were introduced into Chimera 1.1v to generate and view the hydrophobic and hydrophilic interactions.…”