Effect of Chloroquine on Some Carbohydrate Metabolic Pathways: Contents of GHS, Ascorbate and Lipid Peroxidation in the Rat

Abdel-Gayoum, A A; Haider, Syed Saleem; Tash, Fathy; Ghawarsha, K.

doi:10.1111/j.1600-0773.1992.tb00538.x

Cited by 10 publications

(10 citation statements)

References 14 publications

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“…Previous studies have indicated that plasma GSH as well as vitamin C and vitamin E were decreased in CQ treated rats and α-lipoic acid had a better protective effect than silymarin against CQ-induced hepatotoxicity (Abdel Gayoum et al, 1992;Pari and Murugavel, 2004); and our results are in agreement with these published reports. Preincubation of hepatocytes with vitamin C, quercetin and purpuragalin shows protective effects against CQ-induced toxicity in almost all parameters measured.…”

Section: Discussionsupporting

confidence: 95%

“…A depletion of the antioxidant defense system is involved in the mechanism of cytotoxicity.inhibitor; quercetin a specific CYP2C8 inhibitor; quinidine and cimetidine, which inhibit the 2D6 subfamily; and acetone a non-specific CYP450 inhibitor on the cytotoxicity of CQ were investigated.There are few studies in the literature on the role of antioxidants against CQ-induced hepatotoxicity (Dass and Shah, 2000;Pari and Murugavel, 2004). Previous findings indicated that reduced glutathione (GSH), vitamin C and vitamin E were decreased in CQ-treated rats (Abdel Gayoum et al, 1992).The purpose of this study was to investigate the possible mechanisms of CQ hepatotoxicity on freshly isolated rat hepatocytes. As specific objectives, the experiments had in view (a) to evaluate the role and activity of CYP450 family metabolizing enzymes on CQ cytotoxicity, and (b) to test for effects of antioxidants, ATP supplier and cellular GSH in CQ-treated hepatocytes.…”

mentioning

confidence: 95%

“…Previous findings indicated that reduced glutathione (GSH), vitamin C and vitamin E were decreased in CQ-treated rats (Abdel Gayoum et al, 1992).…”

mentioning

confidence: 99%

“…There are few studies in the literature on the role of antioxidants against CQ-induced hepatotoxicity (Dass and Shah, 2000;Pari and Murugavel, 2004). Previous findings indicated that reduced glutathione (GSH), vitamin C and vitamin E were decreased in CQ-treated rats (Abdel Gayoum et al, 1992).…”

mentioning

confidence: 99%

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Cytotoxicity of chloroquine in isolated rat hepatocytes

Jamshidzadeh¹,

Niknahad²,

Kashafi³

2007

J of Applied Toxicology

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Chloroquine is a synthetic quinoline being used as an antimalaria and antirheumatoid agent. Several cases of hepatotoxicity have been reported with the use of chloroquine. However, the mechanism(s) of its hepatotoxic effect is unknown. The purpose of this study was to investigate the cytotoxic mechanism of chloroquine. Cytotoxicity was studied using freshly isolated rat hepatocytes incubated in Krebs-Henseleit buffer under a flow of 95% O(2) and 5% CO(2). Chloroquine was toxic towards hepatocytes and caused cell death with an ED(50) of about 100 mm in 2 h. The events before cell death were rapid GSH depletion and lipid peroxidation. Cytochrome P-450 inhibitors, troleandromycine, cimetidine and quinidine increased the cytotoxicity of chloroquine. Antioxidants significantly prevented the cytotoxicity of chloroquine. Depleting the hepatocyte GSH beforehand increased the chloroquine cytotoxicity. Preventing chloroquine metabolism by specific P-450 inhibitors increased its toxicity, suggesting that a major part of its toxicity is mediated by chloroquine and not by its metabolites. A depletion of the antioxidant defense system is involved in the mechanism of cytotoxicity.

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Section: Discussionsupporting

confidence: 95%

mentioning

confidence: 95%

“…Previous findings indicated that reduced glutathione (GSH), vitamin C and vitamin E were decreased in CQ-treated rats (Abdel Gayoum et al, 1992).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cytotoxicity of chloroquine in isolated rat hepatocytes

Jamshidzadeh¹,

Niknahad²,

Kashafi³

2007

J of Applied Toxicology

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“…According to previous reports, some authors suggested that the drug has inhibitory effect on metabolic pathways of glucose in parasites [8,9] where it was found to inhibit the uptake of glucose by schistosoma [10]. The drug was reported to decrease insulin and glucose levels in rats by interfering with insulin biosynthesis [11], decrease the rate of glucose oxidation in islets of Langerhans [12] and decrease fasting glucose level in rats treated with subchronic level of chloroquine [13]. Others suggested that chloroquine reduces intracellular insulin degradation in vitro [14] and in vivo [15] and inhibits 125 I-insulin degradation in the perfused rat liver [16].…”

Section: Introductionmentioning

confidence: 99%

Effect of Chloroquine on Glucose Metabolism

Gaafar

Khedr²,

Bashandy³

et al. 2011

Arzneimittelforschung

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The long- and short-term effects of chloroquine (CAS 54-05-7) on glucose metabolism in rats were assessed. The long-term chronic chloroquine administration (5 and 10 mg/kg b.w. 6 days a week for 6 months) caused a decrease in serum glucose, insulin, calcium, potassium and protein levels, while the glucagon level increased. The short-term acute effect of chloroquine administration (10 mg/kg b.w. 6 days for one week) caused an improvement in glucose tolerance as shown by the decrease in glucose and insulin curves after an oral glucose tolerance test. This was accompanied by an increase in insulin activity, corrected insulin response, and glucose tolerance parameter and a decrease in glucose and insulin areas. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased, too, indicating an increase which provides the needed energy for overcoming the injurious effect of chloroquine.

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Protective effect of α‐lipoic acid against chloroquine‐induced hepatotoxicity in rats

Pari

Ponnusamy

2004

J of Applied Toxicology

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Oral administration of a-lipoic acid, a metavitamin, was investigated for its possible hepatoprotective effect in Wistar rats against chloroquine-induced toxicity. Rats were treated orally with alpha-lipoic acid (10, 30 and 100 mg x kg(-1) day(-1)) for 7 days before a single oral administration of chloroquine (970 mg x kg(-1) day(-1)) and alpha-lipoic acid treatment was continued for three more days. The increased level of serum enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase), bilirubin, lipids and plasma thiobarbituric acid-reactive substances (TBARS) and hydroperoxides observed in rats treated with chloroquine were very much reduced in rats treated with alpha-lipoic acid plus chloroquine. A significant decrease in plasma antioxidants such as reduced glutathione (GSH), vitamin C and vitamin E were observed in chloroquine-treated rats when compared with control rats. Administration of alpha-lipoic acid significantly improved the levels of plasma antioxidants GSH, vitamin C and vitamin E in chloroquine-treated rats. In the case of 100 mg x kg(-1) day(-1) the effect was highly significant compared with the other doses (10 and 30 mg x kg(-1) day(-1)). The results of the study revealed that alpha-lipoic acid could offer protection against chloroquine-induced hepatotoxicity. alpha-Lipoic acid had a better protective effect when compared with silymarin, a reference drug.

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Effect of Chloroquine on Some Carbohydrate Metabolic Pathways: Contents of GHS, Ascorbate and Lipid Peroxidation in the Rat

Cited by 10 publications

References 14 publications

Cytotoxicity of chloroquine in isolated rat hepatocytes

Cytotoxicity of chloroquine in isolated rat hepatocytes

Effect of Chloroquine on Glucose Metabolism

Protective effect of α‐lipoic acid against chloroquine‐induced hepatotoxicity in rats

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