In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

Abstract

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.

Interaction of aloe active compounds with calf thymus DNA

“…Several previous reports suggested that ALM shows antiproliferative and antitumor activity in human hepatoma, lung carcinoma cell, and human gastric carcinoma cells and also has high specificity for neuroectodermal tumors . Aloin (ALN) (Figure 1B), another aloe active compound, is an anthraquinone glycoside with a variety of pharmacological activities and can inhibit tumor growth and angiogenesis and has potential chemotherapeutic properties . Aloe emodin‐8‐glucoside (ALMG) (Figure 1C) is another structural homolog, a glucoside metabolite of aloe emodin, and has shown antidiabetic properties in the treatment of insulin resistance .…”

Aloin: A natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities

“…This structure was postulated on the basis of in vitro FRAP test, which confirmed the potent reducing potential of aloin (Esmat et al, 2012). In contrast, doxorubicin is a bidentate compound and binds to iron giving rise to Fe 3+ (Dox) 3 complex due to its inability to reduce Fe 3+ to Fe 2+ ions in vitro (Esmat et al, 2012). However, Fe 2+ (Dox) 2 complex might also be formed in vivo due to the prevalence of reducing agents, such as reduced glutathione and NADPH.…”

“…A description of Fe 2+ (aloin) 2 complex has been postulated (Figure 4), which shows the binding of Fe 2+ to two molecules of aloin by two types of bonds: an ionic bond at positions 1 or 8 and a coordinating bond at position 9. This structure was postulated on the basis of in vitro FRAP test, which confirmed the potent reducing potential of aloin (Esmat et al, 2012). In contrast, doxorubicin is a bidentate compound and binds to iron giving rise to Fe 3+ (Dox) 3 complex due to its inability to reduce Fe 3+ to Fe 2+ ions in vitro (Esmat et al, 2012).…”

“…The elevated serum iron concentration favors the intriguing possibility that aloin treatment induces iron overload in the body iron stores (liver, heart, or spleen) and/or increases the hepatic hepcidin mRNA expression, which is under investigation. The IR spectrum of iron-aloin complex (Figure 3b) along with the findings obtained from our recent in vitro study (Esmat et al, 2012) tempted us to report on the chelating affinity of aloin to Fe 2+ ions through its phenolate and carbonyl groups, which act as bidentate iron binding moieties. A description of Fe 2+ (aloin) 2 complex has been postulated (Figure 4), which shows the binding of Fe 2+ to two molecules of aloin by two types of bonds: an ionic bond at positions 1 or 8 and a coordinating bond at position 9.…”

“…In our recent in vitro and in vivo studies (Esmat et al, 2012), we reported that repeated treatment of rats with aloin at its maximum tolerated dose, unlike doxorubicin, does not affect the heart function confirmed by biochemical analyses in the serum and tissue and histological examination of cardiomyocytes by light and transmission electron microscopy. The non-cardiotoxic effect of aloin was explained due to its strong antioxidant and scavenging activities for free radicals and reactive oxygen species, as well as iron-chelating potential, compared with the synthetic standards.…”