Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity

El‐Moselhy, Mohamed A.; El-Sheikh, Azza A. K.

doi:10.1016/j.biopha.2013.09.001

Cited by 85 publications

(56 citation statements)

References 57 publications

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“…[2][3][4][5][6][7][8][9][10][11][12]34 In our study, serum markers that indicate cardiac, hepatic, and renal damage increased significantly 4 days after 30 mg kg À1 DOX was administered, compared with the controls. In the light microscopic examination, histopathologic changes were seen in tissues of the DOX-treated rats.…”

Section: Discussionmentioning

confidence: 85%

Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats

et al. 2015

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Objective: Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats. Methods: Rats were treated with CAR (250 mg kg−1 day−1; intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg−1 α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg−1, i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities. Results: DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues. Conclusion: Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes.

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Section: Discussionmentioning

confidence: 85%

Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats

et al. 2015

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“…Protective effect of atorvastatin has been proven in the intestines (29), brain (30), kidney (15), heart (16), testis (17) and ovary (18) injury against induced ischemia/reperfusion, chemotherapy and irradiation. Chemoprotective and therapeutic effects of ATV has been seen against doxorubicin-induced hepato-renal toxicity (31). Sathyapalan and colleagues showed that ATV in patients with polycystic ovary and hyperandrogenemia reduced inflammation and metabolic parameters after 12 wk (32).…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study

Hamzeh¹,

Hosseinimehr²,

Mohammadi³

et al. 2018

IJRM

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Background:Cyclophosphamide (CP), as an anticancer agent, causes ovarian toxicity and subsequent infertility in women. Atorvastatin (ATV) at a low dose has antioxidant and anti-inflammatory properties.Objective:The aim of this study was to investigate the protective effect of ATV against CP-induced ovarian injury in rat.Materials and Methods:In this experimental study, thirty-two female Wistar rats were randomly divided into four groups as I) control, II) ATV (10 mg/kg), III) CP (150 mg/kg), and IV) CP +ATV. The ATV treated groups were received ATV for 10 days via oral gavage. In the CP+ATV group, ATV was administrated on 5 days before and 5 days after CP injection. Histological structure, apoptosis (caspase-3), oxidative stress parameters as malondialdehyde, reactive oxygen species, protein carbonyl levels and cell viability were evaluated in ovary tissue by histological scores, immunohistochemistry, histochemical and biochemical assays. The levels of estrogen and progesterone hormones were measured on the 12th day of study.Results:ATV pretreatment significantly decreased the levels of oxidative stress biomarkers as malondialdehyde, reactive oxygen species and protein carbonyl levels and increased cell death in CP-treated rats as compared with the CP alone group. ATV significantly increased estrogen and progesterone levels in CP-treated rats. In addition, the histological examination showed ATV mitigated acute inflammation, degenerative cells in stroma and follicles, stromal edema, vacuolization, atresia of the follicles and congestion of blood vessels in the CP-treated animals. Furthermore, ATV significantly reduced immunoreactivity level of caspase-3 in CP-treated rats.Conclusion:Our results showed that the ATV with antioxidant and anti-apoptosis (caspase-3) activities protected ovarian against CP-induced toxicity.

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“…Doxorubicin (DOX) is an antineoplastic used in the fight against various types of cancer and although it is quite effective for this purpose, it has limited clinical use because it causes severe side effects [9]. The mechanism of toxicity of DOX seems to be related to the production of reactive oxygen species (ROS) in the body [10,11]. On the order hand, antioxidants might be used to decrease ROS generated by DXR.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Genotoxic and Antigenotoxic Effects of Andiroba (Carapa guianensis Aublet) Oil and Nanoemulsion on Swiss Mice

Melo

Fascineli

Milhomem-Paixão

et al. 2018

Journal of Nanomaterials

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The Carapa guianensis (andiroba) oil is commonly used by the Amazon population for medicinal purposes. The objective of this study was to determine the genotoxic and antigenotoxic potential of the andiroba oil (AO) and nanoemulsion (AN) using Swiss mice. Therefore, we used the comet assay and micronucleus test. The AO predominant compounds were oleic (39.13%), palmitic (33.22%), and linoleic (16.86%) acids. AN composition obeyed the surfactant/oil ratio of 0.69, and the Tween 80/Span 80 ratio was held at 0.9. Our results showed no cytotoxicity or genotoxicity in the mice treated with AO and AN alone. However, there was a significant reduction in the polychromatic erythrocytes (PCEs) numbers in all groups treated with doxorubicin (DOX), including those pretreated with AO and AN. Thus, the samples tested did not protect against DOX. On the other hand, our results showed a large increase in micronucleus (MN) formation when the mice were treated with DOX alone; these numbers were reduced when the animals were pretreated with AO and AN. The results indicate a protective effect of andiroba on MN formation and show no evidence of genotoxicity in mice.

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Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity

Cited by 85 publications

References 57 publications

Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats

Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats

Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study

Evaluation of the Genotoxic and Antigenotoxic Effects of Andiroba (Carapa guianensis Aublet) Oil and Nanoemulsion on Swiss Mice

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