Evaluation of ambrein and epicoprostanol for their antioxidant properties: protection against adriamycin-induced free radical toxicity.
Ambrein and epicoprostanol were evaluated for their antioxidant potential in vitro by chemiluminescence (CL), as well as in vivo using lipid peroxides and glutathione levels as indicators in liver tissue of rats treated with adriamycin (doxorubicin) a well known free radicals producing drug. In the in vitro test, the inhibition in CL by ambrein was dose dependent. Both the high concentrations of ambrein (20-40 microg/ml) inhibited CL response significantly (P<0.05 and P<0.01, respectively) when compared to control. Similarly two low concentrations (5-20 microg/ml) of epicoprostanol inhibited CL significantly (P<0.001 and P<0.01, respectively) in comparison of DMSO control. The high concentration (40 microg/ml) of epicoprostanol behaved exceptionally and caused an increase in CL response that was more than control and significantly (P<0.001) higher than both the low concentrations. In the in vivo studies adriamycin treatment significantly (P<0.05) increased malondialdehyde (MDA) and decreased non-protein sulfhydryl (NP-SH) contents in the liver tissue of mice after 5 days treatment. Ambrein (25 and 50 mg/kg) treatment as a solo therapy at both the dose levels significantly (P<0.001) decreased MDA contents in the liver tissue. On the other hand, in the combined treatment the high dose effectively prevented any rise in MDA contents and it remained around the levels of ambrein alone. In the same experiment, adriamycin declined NP-SH contents significantly (P<0.001). Ambrein alone at both the dose levels caused a decline (P<0.01) in NP-SH contents when compared to adriamycin group. But in the combined treatment this decline in NP-SH was significantly (P<0.05) different from adriamycin alone. In the experiments dealing with epicoprostanol, adriamycin treatment increased MDA contents significantly (P<0.05) that declined significantly (P<0.001) with epicoprostanol (10- or 20mg/kg) treatment. In the same experiment co-treatment with adriamycin prevented any rise in MDA contents significantly (P<0.001) as it was observed in adriamycin alone group. Although, this treatment failed to prevent any decline in NP-SH contents either alone or in combination with adriamycin. Epicoprostanol itself had the comparative declining effect on the contents of NP-SH as seen in adriamycin group. From the results of our experiments it seems that ambrein at all concentrations behaves like antioxidant in in vitro studies but the same time it decreased NP-SH contents in vivo accompanied by a decline in MDA contents. Whereas, epicoprostanol at two low concentrations had a decline in CL indicating a possible antioxidant potential but the high concentration increased CL showing a tendency towards oxidant prospective. However, in animal studies it has shown a clear protection against adriamycin induced free radical damage.
Raza
Muhammad
M
Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, PO Box 6655, Buraydah 51452, Qassim, Saudi Arabia. mrsheikh@ksu.edu.sa
Alorainy
Mohammad S
MS
Alghasham
Abdullah A
AA
D018648:Ambergris / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002777:Cholestanols / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity; D005609:Free Radicals / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009284:Naphthols / Q000008:administration & dosage / Q000494:pharmacology*; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology
D018648:Ambergris; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002777:Cholestanols; D005609:Free Radicals; D009284:Naphthols; D014315:Triterpenes; C074170:ambrein; D008315:Malondialdehyde; D004317:Doxorubicin; D005978:Glutathione; C523170:epicoprostanol