Premna integrifolia ameliorates cyclophosphamide-induced hepatotoxicity by modulation of oxidative stress and apoptosis

Singh, Chandrashekhar; Prakāsh, Chandra; Tiwari, Kavindra Nath; Mishra, Sunil Kumar; Kumar, Vijay

doi:10.1016/j.biopha.2018.08.039

Cited by 45 publications

(21 citation statements)

References 51 publications

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“…ROS and pro-inflammatory cytokines are the two main factors inducing cell death. Here, CP induced apoptotic cell death as showed by increased BAX and caspase-3 and decreased BCL-2 which coincided with previous studies [1,5,53]. Accumulating evidence indicated that ROS and inflammatory cascade activation induce apoptotic cell death in the liver [1,4,9].…”

Section: Discussionsupporting

confidence: 90%

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

et al. 2019

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Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

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Section: Discussionsupporting

confidence: 90%

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

et al. 2019

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“…In this study, immunosuppressed condition was established via CTX injection, which is one of the most commonly used as a chemotherapeutic treatment for cancers and as an immunosuppressive agent before myeloablative therapies ( Ehrke, 2003 ). Accordingly, the cytotoxicity was reflected in liver which is the first target organ engaging all toxic drugs ( Singh et al, 2018 ), and spleen which is responsible for the immune status by controlling the proliferation of T cells, B cells and lymphocytes ( Gong et al, 2015 ). CTX treatment led to distinctly upregulated liver parameter of alanine aminotransferase, injuries in spleen and disturbed hematological values.…”

Section: Discussionmentioning

confidence: 99%

Pilot Safety Evaluation of a Novel Strain of Bacteroides ovatus

Tan

Wang

et al. 2018

Front. Genet.

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Bacteroides ovatus ELH-B2 is considered as a potential next-generation probiotic due to its preventive effects on lipopolysaccharides-associated inflammation and intestinal microbiota disorders in mice. To study safety issues associated with B. ovatus ELH-B2, we conducted comprehensive and systematic experiments, including in vitro genetic assessments of potential virulence and antimicrobial resistance genes, and an in vivo acute toxicity study of both immunocompetent and immunosuppressed mice via cyclophosphamide treatment. The results indicated that this novel strain is non-toxigenic, fragilysin is not expressed, and most of potential virulence genes are correlated with cellular structures such as capsular polysaccharide and polysaccharide utilizations. The antibiotic resistance features are unlikely be transferred to other intestinal microorganisms as no plasmids nor related genomic islands were identified. Side effects were not observed in mice. B. ovatus ELH-B2 also alleviated the damages caused by cyclophosphamide injection.

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“…The Inadequate activity of catalase cannot degrade H 2 O 2 , and generate OH − radical which results in oxidative injury to liver cells. It has been reported that treatment with cyclophosphamide decreases antioxidant enzyme level 45. Quercetin increases antioxidant enzyme level by its antioxidant action where it reduces itself and prevents oxidation of other enzymes 46.…”

Section: Discussionmentioning

confidence: 99%

“…More pronounced elevation of GSH level was observed noted in LA-Q-ORMOSIL nanoparticle treated group compared to other treatment groups (Figure 9C). GST prevent the cells against peroxidative damage and clear the metabolites of CP through enzymatic catalyzed conjugation reaction 45,49. In the present study, a significant decrease in GST activity in CP-adminisitered rats were seen compared to the control group (Figure 9D).…”

Section: Discussionmentioning

confidence: 99%

<p>Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity</p>

Naqvi

Sharma

Flora

2019

IJN

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ObjectiveThe study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury.MethodologyQ-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50µg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues.ResultsPhysiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury.ConclusionTargeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.

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Premna integrifolia ameliorates cyclophosphamide-induced hepatotoxicity by modulation of oxidative stress and apoptosis

Cited by 45 publications

References 51 publications

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Pilot Safety Evaluation of a Novel Strain of Bacteroides ovatus

<p>Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity</p>

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