Protective effects of crocetin on the bladder toxicity induced by cyclophosphamide.
Cyclophosphamide (CX) has been widely used as an anticancer agent, however obtaining a maximum therapeutic potential for CX has remained a challenge, for generating undesired toxic side effects to the bladder. Crocetin, a natural carotenoid has been employed in the present studies to ameliorate the bladder toxicity of CX. Interestingly, crocetin at a dose of 50 mg/kg modulated the release of chloroacteldehyde, a urotoxic metabolite of CX in the urine of mice given combined treatment. Crocetin at the same dose significantly elevated Glutathione-S-Transferase enzyme activity both in the bladder and the liver of mice treated with CX. The exact mechanism of the protective effect of crocetin is not known, presumable it may act as an antioxidant, trapping and scavenging free radicals during the detoxification process. In Sarcoma-180 tumor bearing mice, crocetin has the ability to protect against CX induced bladder toxicity without altering its antitumor activity. Our studies are important to identify antioxidant rescue agents to overcome dose-limiting toxicity of CX.
Nair
S C
SC
University of Minnesota Medical School, Minneapolis 55455.
Panikkar
K R
KR
Parthod
R K
RK
D000818:Animals; D002338:Carotenoids / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use / Q000633:toxicity*; D005982:Glutathione Transferase / Q000032:analysis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D012510:Sarcoma 180 / Q000188:drug therapy*; D013053:Spectrophotometry; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology; D014801:Vitamin A / Q000031:analogs & derivatives
C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D003520:Cyclophosphamide; D005982:Glutathione Transferase