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The Village News Inc. ©2006
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Joe Naiman
Village News Correspondent
4/7/2006 7:34:07 PM
Chemotherapy and other anti-cancer drugs may have toxic side effects themselves, but research at the J.S.S. College of Pharmacy in India indicates that a flavonoid found in all citrus fruits may reduce the toxicity of treatments using the antibiotic doxorubicin.
A poster presentation March 8 at the Society of Toxicology convention in San Diego covered some of the work of Satish Kumar Nataraj, Rajasekar Reddy, Elango Kannan, and Suresh Bhojraj, all of whom are associated with the Department of Pharmacology and Toxicology at J.S.S. College of Pharmacy in Ootacamund, India. The presentation was titled “Chemoprotective Potential of Naringenin, a Naturally Occurring Citrus Flavanone, in Doxorubicin Induced Clastogenicity.” Nataraj was present during the display of the poster.
“Natural citrus flavonoid, it is really useful in doxorubicin-induced anti-cancer drugs,” Nataraj said. “It reduces a lot of toxic effects of the anti-cancer drugs.”
Doxorubicin is an anthracycline antibiotic with the potential to be a chemotherapeutic agent, but clinical uses have been restricted due to its dose-limiting toxicity in normal, healthy cells. The effects include cardiotoxicity (heart), myelotoxicity (spinal cord or bone marrow), and hematological (blood) toxicity, which are possibly caused by increased oxidative stress.
Naringenin is found in all citrus fruits, and the effect of naringenin on doxorubicin-induced clastogenicity (the ability to cause structural changes of chromosomes) in albino mice was investigated by the J.S.S. College of Pharmacy researchers. The findings indicated that the frequency of micronuclei was decreased in mice pre-treated with naringenin and that there was also a significant decline in the percentage of apoptotic cells when doxorubicin was used to induce apotosis (programmed cell death) in cells. It is believed that the free radical scavenging and antioxidant nature of naringenin may be one of the reasons that the flavonoid inhibits doxorubicin toxicity, since the antioxidant activity of naringenin has previously been documented.
The study used 40 Swiss albino male mice aged eight to ten weeks and weighing between 25 and 30 grams. The mice were divided equally into eight different treatment and control groups. One control group received one milliliter of distilled water per kilogram of body weight, a second group received 15 milligrams of doxorubicin per kilogram of body weight but no naringenin, three groups received different dosages of naringenin but no doxorubicin, and three other groups received those three different amounts of naringenin along with 15 milligrams per kilogram of body weight of doxorubicin. The naringenin used was dissolved in a small volume of ethanol and diluted with distilled water before being administered for seven days. The three groups of mice receiving both naringenin and doxorubicin were injected with doxorubicin simultaneously with the last dose of naringenin. Stained slides were observed under 400x magnification.
The experiments also treated V79 cells in their exponential phase of growth with concentrations of naringenin and doxorubicin for three hours; those cells were incubated for up to 72 hours.
The four groups which did not receive doxorubicin had no significant difference in the toxic cell percentage while more than a sixfold increase in the group administered doxorubicin but not naringenin was observed compared to the control group. All three groups administered both doxorubicin and naringenin had reductions in toxicity with those administered 30-milligram doses per kilogram of body weight having toxicity reduced by 60 percent from that of the doxorubicin-only group.
The research on mice has taken about three years, and tests will subsequently be conducted upon rabbits. Nataraj estimates that clinical trials on humans will begin in approximately three years if the work on the rabbits proves successful.
Since the naringenin does not have toxicity itself, it can be used during the entire treatment. “It can be used for months,” Nataraj said. “During the whole time we can administer this naringenin.”
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