Effects of an antimitotic agent (cyclophosphamide) on plasma lipoproteins

Loudet, Anne-Marie; Dousset, N.; Carton, Michel; Douste‐Blazy, Louis

doi:10.1016/0006-2952(84)90594-x

Cited by 17 publications

(10 citation statements)

References 22 publications

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“…The pathogenesis of CP-induced cardiotoxicity was attributed to an increase in free oxygen radicals and a decrease in the antioxidant defense mechanism by CP in the heart [12]. Hypercholesterolemia, hypertriglyceridemia, and impaired secretion of heart lipoprotein lipase have been reported in CP-treated rabbits [13,14]. Moreover, it has been reported that CP induced its acute cardiotoxicity by increasing inner mitochondrial membrane permeability to calcium and decreasing the activities of Krebs cycle enzymes with the consequent uncoupling of mitochondrial-linked ATP synthesis [15,16].…”

Section: Introductionmentioning

confidence: 98%

Thymoquinone supplementation attenuates cyclophosphamide‐induced cardiotoxicity in rats

Nagi

Al‐Shabanah

Hafez

et al. 2010

J Biochem & Molecular Tox

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This study examined the possible protective effects of thymoquinone (TQ), the main constituent of the volatile oil of black seed (Nigella sativa), against cyclophosphamide (CP)-induced cardiotoxicity. Adult male Wistar albino rats were divided into four treatment groups. Rats in the first group were served as control. Rats in the second group received TQ (50 mg/L in drinking water) for 12 days. Animals in the third group were injected with a single dose of CP (200 mg/kg, IP) at day 5. Rats in the fourth group received TQ (50 mg/L in drinking water) for 5 days before a single dose of CP (200 mg/kg, IP) and continued thereafter throughout the experiment. On day 13, animals were sacrificed; serum and hearts were isolated and analyzed. Cyclophosphamide resulted in a significant increase in serum creatine kinase, lactate dehydrogenase, cholesterol, triglycerides, creatinine, urea, and tumor necrosis factor-α. In heart tissues, CP resulted in a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione, glutathione peroxidase, catalase, and adenosine triphosphate levels. Interestingly, TQ supplementation resulted in a complete reversal of all the biochemical changes induced by CP to their control values. Data from this study suggest that TQ supplementation attenuates CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to decrease oxidative and nitrosative stress and to preserve the activity of antioxidant enzymes as well as its ability to improve the mitochondrial function and energy production. .

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Section: Introductionmentioning

confidence: 98%

Thymoquinone supplementation attenuates cyclophosphamide‐induced cardiotoxicity in rats

Nagi

Al‐Shabanah

Hafez

et al. 2010

J Biochem & Molecular Tox

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“…[3] Moreover, CP is associated with hypercholesterolemia, hypertriglyceridemia, and impaired secretion of heart lipoprotein lipase. [4] CP-induced alterations of lipid metabolism pathways in various conditions lead to myocardial lipid accumulation and lipotoxic cardiomyopathy. [5]…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against cyclophosphamide-induced myocardial damage

Chakraborty

Kamath²,

Bhattacharjee³

2014

Toxicol Int

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Objective:Treatment of ischemic hypertensive patients with hydrochlorothiazide can precipitate cardiac arrhythmias. Green tea by virtue of its antioxidant potential is responsible for cardio-protective activity. The present study was undertaken to evaluate the pharmacodynamic interaction of green tea extract with hydrochlorothiazide against cyclophosphamide-induced myocardial toxicity.Materials and Methods:Rats were treated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of green tea extract in alone and interactive groups for 10 days. Standard, high, and low dose of interactive groups received hydrochlorothiazide (10 mg/kg, p.o.) for last 7 days. Apart from normal control, all other groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on day first and the effects of different treatments were evaluated by changes in electrocardiographic parameters, serum biomarkers, and tissue antioxidant levels. Apart from that, lipid profile and histological studies were also carried out.Results:Compared to cyclophosphamide control group, both high and low dose of green tea exhibited significant decrease in serum biomarkers and increase in tissue antioxidant levels. Green tea treatment was also responsible for significant improvement in echocardiography (ECG) parameter, lipid profile, and histological score. Incorporation of high and low dose of green tea with hydrochlorothiazide-exhibited significant protection compared to hydrochlorothiazide-alone-treated group.Conclusion:The present findings clearly suggested that green tea extract dose dependently reduces cyclophosphamide-induced myocardial toxicity. Green tea when combined with hydrochlorothiazide can reduce the associated side effects and exhibits myocardial protection.

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“…The pathogenesis of CP-induced acute cardiotoxicity was attributed to the increase in free oxygen radicals and the decrease in the antioxidant defense mechanism by CP in the heart [6]. Hypercholesterolemia, hypertriglyceridemia and impaired secretion of heart lipoprotein lipase have been reported in CP-treated rabbits [7, 8]. Lipid homeostasis plays a central role in the pathogenesis of primary and/or secondary alterations of lipid metabolism pathways in various conditions lead to myocardial lipid accumulation and lipotoxic cardiomyopathy [9].…”

Section: Introductionmentioning

confidence: 99%

Probucol Attenuates Cyclophosphamide‐induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

Asiri

2010

Oxidative Medicine and Cellular Longevity

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Cyclophosphamide (CP) is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control) and second (probucol) groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day), respectively, for two weeks. Animals in the third (CP) and fourth (probucol plus CP) groups were injected with the same doses of corn oil and probucol (61 mg/kg/day), respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.). The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) (117%), lactate dehydrogenase (LDH) (64%), free (69%) and esterified cholesterol (42%) and triglyceride (69%) compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP) (40%) and ATP/ADP (44%) in cardiac tissues. Probucol pretreatment not only counteracted significantly the CP-induced increase in cardiac enzymes and apoptosis but also induced a significant increase in mRNA expression of antioxidant enzymes and improved ATP, ATP/ADP, glutathione (GSH) in cardiac tissues. In conclusion, data from the present study suggest that probucol prevents the development of CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to increase mRNA expression of antioxidant genes and to decrease apoptosis in cardiac tissues with the consequent improvement in mitochondrial oxidative phosphorylation and energy production.

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Effects of an antimitotic agent (cyclophosphamide) on plasma lipoproteins

Cited by 17 publications

References 22 publications

Thymoquinone supplementation attenuates cyclophosphamide‐induced cardiotoxicity in rats

Thymoquinone supplementation attenuates cyclophosphamide‐induced cardiotoxicity in rats

Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against cyclophosphamide-induced myocardial damage

Probucol Attenuates Cyclophosphamide‐induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

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