Context: The antitumor activity of aloin, the active anthraquinone of Aloe juice, against different murine and human tumors has been reported. Objective: In the present study, the impact of repeated aloin treatment at its maximum tolerated dose on serum levels of lipid profile, some elements, iron status and kidney function, compared with doxorubicin (a cardiotoxic anthracycline and inhibitor of erythropoiesis), was assessed. Materials and methods: Rats were treated with a single dose of doxorubicin (30 mg/kg body weight, intraperitoneal) or aloin (50 mg/kg body weight, intramuscular) twice weekly over 2 weeks. Results: Acute doxorubicin treatment elevated serum levels of triacylglycerols (59.90%), total cholesterol (42.29%), cholesteryl esters (54.75%), low density lipoprotein-cholesterol (230.16%), very low density lipoprotein-cholesterol (56.42%), urea (287.53%), and creatinine (85.38%), whereas serum high density lipoprotein-cholesterol, sodium, and calcium levels were reduced (44.61, 9.61, and 9.76%, respectively), as compared with controls. In contrast, aloin treatment showed insignificant changes in all the aforementioned parameters. Both doxorubicin and aloin induced erythropoiesis impairment demonstrated by a reduction in blood hemoglobin concentration. While aloin treatment elevated serum iron level (30.28%), doxorubicin treatment reduced serum levels of iron (51.47%) and percent transferrin saturation (55.21%), and in contrast, increased serum total iron binding capacity (34.85%). The chelating affinities of iron-aloin and -doxorubicin complexes, which contain bidentate iron-binding moieties, have been shown in the infrared spectra. Discussion and conclusion: The non-cardiotoxic effect of aloin treatment was due to its non-atherogenic and iron-chelating activities, which might also contribute in part to its anti-proliferative activity.
Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV In the present study, the cardiotoxicity of aloin, a naturally occurring anthraquinone glycoside with antiproliferative activity was compared with doxorubicin, a cardiotoxic anthracyline drug, in rats. The antioxidant and iron‐chelating activities of aloin and doxorubicin in vitro were also evaluated. Rats treated with aloin (50 mg/kg body weight, intramuscular)) twice weekly over 2 weeks showed no signs of cardiotoxicity as assessed by an absence of changes in relative heart weight, serum level of heart function enzymes, and a lack of degeneration in the myocardium of the left ventricle. Acute doxorubicin administration (30 mg/kg body weight, intraperitoneal) to rats produced severe cardiotoxicity as supported by biochemical and histological studies. Aloin did not induce oxidative stress or enhance the endogenous antioxidant defense system in the heart. In vitro antioxidant tests showed that aloin, in contrast to doxorubicin, had substantial antioxidant activity represented by scavenging of 1,1‐diphenyl 2‐picrylhydrazyl and nitric oxide· radicals, inhibition of lipid peroxidation, and ferric‐reducing antioxidant activity in addition to iron chelating potential. Ventricular inducible nitric oxide synthase protein expression was unaffected by either aloin and doxorubicin treatments. In conclusion, repeated aloin treatment, in contrast to that of doxorubicin, failed to produce oxidative stress‐induced cardiotoxicity in the rats.
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