Polyphenolic fraction of Algerian propolis reverses doxorubicin induced oxidative stress in liver cells and mitochondria

Doxorubicin [DOX] is a potent anticancer drug; its use has been limited by its hepatotoxicity, which is due to free radicals generation.Propolis, a honeybee product very rich in flavonoids and therapeutic possibilities, has gained popularity as a food and alternative medicine. The present study treats DOX pro-oxidant effect on hepatic cells and mitochondrial functions. The prophylactic effect of propolis ethanolic extract [EEP] against DOX induced mitochondrial oxidative stress has also been investigated. We find that doxorubicin at the amount of 10 mg/Kg altered liver mitochondrial functions as attested by the overproduction of superoxide anion [O[2][-]] by mitochondrial respiratory chain complex III. The hepatic tissue from DOX treated rats showed also a marked depletion in reduced GSH contents and an inhibition in [Mn-SOD], [Cu-Zn SOD] and [CAT] enzymatic activities. DOX increase cytosolic and mitochondrial lipid peroxidation as attested by the MDA content. These results are reversed after one month per os pretreatment by EEP at the amount of 100 mg/kg. Propolis polyphenolic fraction protects liver tissue from oxidative stress by protecting mitochondrial functions and reinforcement of enzymatic and non enzymatic antioxidants

Efficiency of propolis extract against mitochondrial stress induced by antineoplasic agents (doxorubicin and vinblastin) in rats.

To assess the oxidative stress and mitochondrial dysfunction associated with disease, toxic process and aging, in vivo and in vitro preventive effect of propolis extract against mitochondrial oxidative stress induced by two anticancer drugs (doxorubicin and vinblastin) have been investigated in female wistar rat using liver and heart mitochondria. The results show that doxorubicin and vinblastin altered mitochondrial functions as observed by a decrease in respiratory control value, an activation of swelling and overproduction of superoxide anion. Myocardial tissue from doxorubicin treated rats showed a marked increase in malondialdehyde production, a depletion of reduced glutathione contents and an inhibition of catalase and superoxide dismutase activities. Similar results were also observed in liver tissue. Pretreatment of rats with propolis extract (100 mg/kg/day po) (10(-4) M ip) administered 4 days prior to doxorubicin (20 mg/kg) and/or vinblastin (2 mg/kg) injection, substantially reduced the peroxidative damage in myocardium and hepatic tissues and markedly restored the tissues catalase and SOD activities. The results strongly suggest that propolis extract protects heart and liver tissues from oxidative stress by protecting the mitochondria.