Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats

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Title
Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats
Author(s)
S H Kim; In Chul Lee; H S Baek; In Sik Shin; C Moon; C S Bae; S H Kim; J C Kim; Hyoung-Chin Kim
Bibliographic Citation
Food and Chemical Toxicology, vol. 64, pp. 110-118
Publication Year
2014
Abstract
This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced acute urotoxicity in rats. CP caused severe hemorrhagic cystitis as shown by significant increases in bladder weight, edema, and hemorrhage as well as increased urinary bladder epithelial cell apoptosis, protein expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and phase II enzymes (i.e., NAD(P)H: quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1)), immunostaining intensity of acrolein-protein adducts, and histopathological changes. The significant decreases in glutathione content and catalase, glutathione S-transferase, and glutathione reductase activities and a significant increase in malondialdehyde content indicated that CP-induced bladder injury was mediated through oxidative stress. In contrast, pretreatment with DADS significantly attenuated the CP-induced urotoxic effects, including oxidative damage, histopathological lesions, apoptotic changes, and accumulation of acrolein-protein adducts in the bladder. DADS also significantly increased expression of CYP2B1/2, CYP3A1, Nrf-2, NQO-1, and HO-1 and significantly decreased expression of CYP2C11. These results indicate that DADS prevented CP-induced bladder toxicity, in part, by detoxifying acrolein. The protective effects of DADS may be due to its ability to decrease metabolic activation of CP by inhibiting CYP2C11 and inducing CYP3A1, and its potent antioxidant activity and antiapoptotic effects occurred via the Nrf-2-antioxidant response element pathway.
Keyword
CyclophosphamideCytochrome P450Diallyl disulfideNrf-2Oxidative stressUrotoxicity
ISSN
0278-6915
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.fct.2013.11.023
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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