Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats
•Diallyl disulfide (DADS) protected bladder against toxicity caused by cyclophosphamide (CP).•DADS decreased CP-induced oxidative stress.•DADS reduced CP-induced apoptosis and protein–acrolein adducts accumulation.•DADS inhibited the metabolic activation of CP. This study investigated the protective...
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Published in | Food and chemical toxicology Vol. 64; pp. 110 - 118 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.02.2014
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | •Diallyl disulfide (DADS) protected bladder against toxicity caused by cyclophosphamide (CP).•DADS decreased CP-induced oxidative stress.•DADS reduced CP-induced apoptosis and protein–acrolein adducts accumulation.•DADS inhibited the metabolic activation of CP.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0278-6915 1873-6351 |
DOI: | 10.1016/j.fct.2013.11.023 |