Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model

Hamzeh, Maedeh; Hosseinimehr, Seyed Jalal; Khalatbary, Ali Reza; Mohammadi, Hamid; Dashti, Ayat; Amiri, Fereshteh Talebpour

doi:10.4103/1735-5362.236837

Cited by 31 publications

(7 citation statements)

References 40 publications

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“…This study observed decreased hepatic antioxidants (GPx, CAT, GSH, SOD, and GSH) with increased MDA levels in CP-treated. This observation is in unison with earlier reports [26,27]. However, hepatic antioxidants were up-regulated whereas MDA levels were down-regulated in rats post-treated and cotreated with DEXA with most remarkable effects observed in rats pre-treated with DEXA.…”

Section: Discussionsupporting

confidence: 90%

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Dexamethasone Attenuates Cyclophosphamide-induced Hepatotoxicity in Albino Rats

Adikwu

Ezerioha

Kemelayefa

2020

Egyptian Journal of Basic and Clinical Pharmacology

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Cyclophosphamide (CP) has appreciably improved survival rate in cancer patients, but the occurrence of hepatotoxicity may undermine its use. This study assessed the potential of dexamethasone (DEXA) to prevent CP-induced hepatotoxicity in albino rats. Thirty-six adult male albino rats were randomised in to six groups of n = 6. Group I (Control) was treated with a dose of normal saline (0.3mL) intraperitoneally (i.p.) for 24 hr. Group II was treated with a dose of DEXA (1mg/kg) ip for 24 hr. Group III was treated with a dose of CP (150mg/kg) i.p for 24 hr. Group IV was treated i.p with a dose of CP (150 mg/kg) for 24hr before treatment with a dose of DEXA (1mg/kg) for 24 hr. Group V was co-treated with a dose of DEXA (1mg/kg) and a dose of CP (150mg/kg) i.p for 24hr. Group VI was pre-treated with a dose of DEXA (1mg/kg/ day) for 24 hr before treatment with a dose of CP (150mg/kg) ip for 24 hr. The rats were anesthetized after treatment; liver samples were excised and evaluated for histology and biochemical markers. Sera were obtained from blood samples and assessed for liver function markers. Liver glutathione, catalase, superoxide dismutase and glutathione peroxidase levels were decreased significantly (p < 0.001) whereas malondialdehyde levels were increased significantly (p < 0.001) in CP-treated rats when compared to control. Significant (p < 0.001) elevations in serum and liver aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, conjugated bilirubin, lactate dehydrogenase and total bilirubin levels occurred in CP-treated rats when compared to control. The liver of CP-treated rats showed hepatocyte necrosis. Interestingly, the aforementioned alterations were significantly reversed in rats post-treated (p < 0.05), co-treated (p < 0.01) and pre-treated (p < 0.001) with DEXA when compared to CP. DEXA may be re-purposed as treatment for CP associated hepatotoxicity.

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Section: Discussionsupporting

confidence: 90%

“…• This study used CP (150 mg/kg) [15] and modified dose of DEXA (1mg/kg ) [16] diluted with normal saline…”

Section: Dose Selection and Animal Treatmentmentioning

confidence: 99%

Dexamethasone Attenuates Cyclophosphamide-induced Hepatotoxicity in Albino Rats

Adikwu

Ezerioha

Kemelayefa

2020

Egyptian Journal of Basic and Clinical Pharmacology

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“…The excess NAPQI unbound to GSH may enter a rapid reaction with the mercapto groups of cellular proteins leading to the production of excessive ROS. Lipid peroxidation is initiated and in turn eventually results in hepatic architecture destruction, apoptosis, or necrosis ( 18 ). In the current study; besides their GSH enhancing effect, the administration of flavonoids ( 1 2 3 4 5 6 ) decreased the level of MDA that was triggered as a result of injection of a high dose of paracetamol.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective effect of kaempferol glycosides isolated from Cedrela odorata L. leaves in albino mice

Asaad

Abdallah

Mohammed

et al. 2021

Research in Pharmaceutical Sciences

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Background and purpose: Paracetamol is the most implicated xenobiotic in inducing hepatotoxicity. Our study aimed to determine the impact of some kaempferol glycosides isolated from the leaves of Cedrela odorata L. on paracetamol hepatotoxicity. Experimental approach: The methanolic extract of dried leaves of C. odorata L . was subjected to the combination of spectroscopic methods ( 1 H and 13 CNMR). Six kaempferol glycosides were isolated: kaempferol-3- O -β-D-glycopyranoside (astragalin), kaempferol-3- O -β-L-rhamnopyranoside, kaempferol-3- O -β-D-rutinoside, kaempferide-3- O -β-D-rutinoside, kaempferide-3- O -β-Drutinosyl-7- O -β-D-rhamnopyranoside, and kaempferol-3- O -β-D- rutinosyl-7- O -a-D-arabinopyranoside. Fifty-four female Swiss Albino mice were divided randomly into 9 groups including (1) control negative (1 mL/kg saline; IP), (2) control positive (paracetamol 300 mg/kg; IP), (3) silymarin 50 mg/kg (IP). Animals of groups 4-9 were injected with 6 different samples of isolated compounds at 100 mg/kg (IP). One h later, groups 3-9 were injected with paracetamol (300 mg/kg IP). Two h later, tissue samples were taken from all animals to assess nitrotyrosine, c-Jun N-terminal protein kinase (c-JNK), Raf -1kinase, and oxidative stress biomarkers viz . reduced glutathione (GSH) and malondialdehyde (MDA). Findings/Results: Isolated glycosides had a prominent anti-apoptotic effect via inhibition of c-JNK and Raf-1 kinase. They also exerted a powerful antioxidant effect by modulating the oxidative stress induced by paracetamol via increasing GSH, reducing MDA and nitrotyrosine concentrations compared to positive control. The glycoside (1) showed a better effect than silymarin (standard) in ameliorating the formation of nitrotyrosine, Raf-1 kinase, c-JNK, and GSH. Conclusion and implication: Kaempferol glycosides isolated for the first time from C. odorata L. leaves exerted antioxidant and antiapoptotic effects via amelioration of oxidative stress and inhibition of Raf/MAPK pathway.

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“…The production of elevated levels of free radicals and lipid peroxidation following Merc administration could damage intracellular proteins and DNA of the kidney which finally the apoptosis occurs. This phenomenon could be characterized as the universal process of hazardous agents ( 34 ). This study emphasized the antioxidant activity of Harm along with other plants with beneficial therapeutic effects by suppressing apoptosis in hazarded tissues.…”

Section: Discussionmentioning

confidence: 99%

Harmine protects mercuric chloride kidney-induced injury by antioxidant activity in male mice: a biochemical and histological study

et al. 2020

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Background and purpose: Mercuric chloride (Merc) can cause kidney toxicity. Harmine (Harm), an herbal alkaloid has various pharmacological and medicinal effects mainly because of its antioxidant activity. In this study, therefore, Harm's protective mechanisms on Merc-induced nephrotoxicity in BALB/c male mice were investigated. Experimental approach: Forty-eight male mice were randomly divided into six groups (n = 8). Groups were received saline, Merc (0.5 mL/day of 0.5 ppm aqueous), Harm (5, 10, 15 mg/kg/day), Merc + Harm (5, 10, 15 mg/kg/day) for 14 consecutive days. Saline and Harm were administrated intraperitoneally and Merc dissolved in drinking water. Urea and creatinine serum levels, body weight, kidney weight, quantitative and qualitative histological alterations, apoptosis rate, total antioxidant capacity (TAC), superoxide dismutase (SOD), and nitric oxide (NO) levels were evaluated. Findings/Results: There was a significant reduction in total body and kidney weights, renal histological criteria, TAC, SOD levels in the Merc group compared to the control group ( P < 0.05), whereas these parameters in the Merc + Harm groups, were significantly increased compared to the Merc group ( P < 0.05). Urea and creatinine serum levels, levels of NO, and apoptosis were significantly higher in the Merc group than the control, while these parameters were decreased in the Merc + Harms groups in comparison with the Merc group ( P < 0.05). Conclusion and implications: Harm protected Merc-induced renal damage in mice. This protection was observed in both histological and biochemical respects. The beneficial effect of Harm was related to its antioxidant properties that diminish NO production and apoptosis induction in the kidney.

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Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model

Cited by 31 publications

References 40 publications

Dexamethasone Attenuates Cyclophosphamide-induced Hepatotoxicity in Albino Rats

Dexamethasone Attenuates Cyclophosphamide-induced Hepatotoxicity in Albino Rats

Hepatoprotective effect of kaempferol glycosides isolated from Cedrela odorata L. leaves in albino mice

Harmine protects mercuric chloride kidney-induced injury by antioxidant activity in male mice: a biochemical and histological study

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