digitoxigenin and Cardiovascular-Diseases

The importance of glycoside in the regulation of thyroid dysfunction is not well understood. In the present investigation, effects of periplogenin-3- O-D-glucopyranosyl (1→6)(1→4)-D-cymaropyranoside, isolated from the vegetable, LAGENARIA SICERARIA, in L-thyroxine (L-T₄)-induced hyperthyroidism and in related cardiovascular abnormalities have been revealed in Wistar albino rats. L-T₄ (500 μg/kg, s. c./d) administration for 12 days significantly increased serum concentrations of thyroxine (T₄), triidothyronine (T₃), and hepatic 5'-deiodinase I (5'-DI) activity with a parallel increase in lipid peroxidation (LPO) in different organs such as heart, liver and kidney; serum glucose and insulin concentrations and a decrease in cardiac Na (+)-K (+)-ATPase activity as well as serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and triglycerides. Most of these adverse effects were reversed following the administration of isolated periplogenin. However, out of its 3 different concentrations (5.0, 10, and 25 mg/kg), 5 mg/kg appeared to be the most effective one as it could nearly normalize the level of T₃, glucose, insulin, Na (+)-K (+)-ATPase activity, tissue LPO and different serum lipids suggesting the protective role of periplogenin against thyrotoxicosis and associated cardiovascular problems. It appears that the periplogenin actions are mediated through its direct antithyroidal and/or LPO inhibiting properties.

Topics: Animals; Cardiovascular Diseases; Digitoxigenin; Humans; Hyperthyroidism; Lipid Peroxidation; Magnoliopsida; Plant Extracts; Random Allocation; Rats; Rats, Wistar; Thyroxine

Doxorubicin is a common chemotherapeutic anticancer drug. Its use is associated with adverse effects including cardiotoxicity. Several therapeutics interventions have been attempted to reduce the toxicity and to improve the efficacy of the drug. However, on phytochemicals very few investigations have been made. In the present study we have evaluated the potential of a cardenolide, periplogenin, isolated from the leaves of Aegle marmelos in protecting the doxorubicin induced cardiotoxicity and lipid peroxidation (LPO) in rats. Doxorubicin induced cardiac and hepatotoxicity were characterized by marked biochemical changes including an increase in serum creatine kinase-MB (CK-MB), glutamate-pyruvate transaminase (SGPT), and tissue LPO, with a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). It also increased the levels of different serum lipids, but decreased the amount of high-density lipoprotein (HDL). Cotherapy of the test cardenolide and doxorubicin for 4 weeks reversed all these adverse effects. However, out of three different concentrations (12.5, 25, and 50 mg/kg p.o.) of the test periplogenin, 25 mg/kg appeared to be most effective. When its efficacy was compared with that of vitamin E (alpha-tocopherol) the isolated compound exhibited a better therapeutic potential. The isolated periplogenin from the leaves of A. marmelos could potentially inhibit doxorubicin-induced cardiovascular problems in rats. However, its moderate dose was found to be most effective.

Topics: Aegle; Alanine Transaminase; alpha-Tocopherol; Animals; Antibiotics, Antineoplastic; Antioxidants; Body Weight; Cardiovascular Diseases; Catalase; Chemical and Drug Induced Liver Injury; Creatine Kinase, MB Form; Digitoxigenin; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin; Glutathione; Lipid Peroxidation; Lipids; Liver Diseases; Plant Leaves; Rats; Rats, Wistar; Superoxide Dismutase