S-Allylcysteine Ameliorates Doxorubicin Toxicity in the Heart and Liver in Mice

Abstract

Doxorubicin, a potent anticancer drug, is effective against a wide range of human neoplasms. However, the clinical uses of doxorubicin have been limited due to its serious cardiotoxic effects, which are likely the result of generation of free radicals and lipid peroxidation. S-Allylcysteine (SAC), an organosulfur compound purified from garlic, has been reported to have antioxidant and radical scavenging effects. Thus, we examined the effect of SAC on doxorubicin toxicity in mice. Severe doxorubicin toxicity was induced in mice by a single intraperitoneal injection (15 mg/kg body weight). SAC (30 mg/kg) was injected intraperitoneally daily for 5 days, starting two days prior to the administration of doxorubicin. Body weight was measured every alternate day. A measurement of serum creatine phosphokinase (CPK) and a histopathological analysis of the heart and liver was performed 6 days after the administration of doxorubicin. Death of any of the animals was recorded during the observation period. Doxorubicin injection induced a mortality rate of 58%, with SAC treatment reducing the doxorubicin-induced mortality rate to 30%. The severe body weight loss caused by doxorubicin (13%) was also significantly attenuated by SAC treatment (9%). Although an elevation of the level of serum CPK was observed following doxorubicin injection (5472 +/- 570 i.u./L), treatment with SAC significantly reduced the level of CPK (1923 +/- 635 i.u./L). Histological analysis demonstrated that heart and liver damage was significantly less severe in SAC treated mice than in mice receiving only doxorubicin. These results suggest that SAC research may ultimately lead to a resolution of the adverse effects of doxorubicin treatment in cancer chemotherapy.

Cytoprotectivity of the natural honey against the toxic effects of Doxorubicin in mice

“…Similar results were obtained following treatment with DOX which has been interpreted as due to fatty infiltration of hepatic tissues [14] and ingestion of 100 mg/Kg of Aspartame [37]. The extensive cellular necrosis detected in the hepatic tissues of mice following DOX injection and the increase in inflammatory cells are concomitant with results of Samelis et al [38].…”

“…There has been a significant difference in demorphism and activities of mice treated with DOX and between those treated with DOX + honey. This difference might refer to the potency of honey to protect or to minimize the deteriorating effects of DOX via reducing free H 2 O 2 radicals [8,9] minimizing lipophosphate (LPO) which destroys the plasma membranes leading to many pathological and cellular changes [12][13][14][15][16]. Daily ingestion of honey therefore could protect body from many toxic effects of DOX or other chemicals.…”

“…These free radicals are believed to have a destructive role via provoking cells to produce H 2 O 2 radicals which react with lipids forming lipid peroxides (LPO) which destroy the plasma membranes leading to many pathological and cellular changes in a few body parts, e.g. heart [12], kidneys [13], liver [14,15] and genital organs [16].…”

Antioxidant capacity, total phenolic and ascorbate content as a function of the genetic diversity of leek (Allium ampeloprasum var. porrum)

“…The Allium genus, which includes about 700 species, has been recognised as a rich source of secondary metabolites (Havey, Galmarini, Gokce, & Henson, 2004). Its organosulphur compounds, responsible for the organoleptic parameters, are implicated as contributing in part to its health-promoting properties (Lanzotti, 2006;Mostafa, Mima, Ohnishi, & Mori, 2000;Singh et al, 1998;Xiao, Pinto, Gundersen, & Weinstein, 2005;Yin, Hwang, & Chan, 2002). In addition, a wealth of other classes of compounds, such as polyphenolics including flavonol glycosides are also suggested to contribute to the healthpromoting properties of these species (Lanzotti, 2006).…”

S-allyl cysteine prevents CCl4-induced acute liver injury in rats

“…There are several reports regarding the biological effects of SAC in different organs. For example, SAC reduces ischemic brain edema in rats by inhibiting lipid peroxidation [7,11], and reduces histological damage to the heart and liver in mice treated with doxorubicin, an anticancer drug [15]. Recently, we reported that SAC attenuates carbon tetrachloride (CCl 4 )-induced pulmonary fibrosis in rats (in press) [15].…”