Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice

Abstract

AimTo investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphoma-bearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone.MethodsThe hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, De Ritis ratio, and coenzyme A fractions by McDougal assay. Glutathione level in animal tissues was measured with Ellman reagent, and the activity of glutathione reductase, transferase, and peroxidase was measured using standard biochemical assays.ResultsD-pantethine (500 mg/kg) and, to a lower extent, selenomethionine (600 µg/kg) partially reduced the negative side effects (leukocytopenia and erythropenia) of Dx (5 mg/kg) in NK/Ly lymphoma bearing animals on the 14th day of their treatment. This increased animal survival time from 47-48 to 60+ days and improved the quality of their life. This ability of D-pantethine and selenomethionine was realized via hepatoprotective and immunomodulating activities. D-pantethine also restored the levels of acid-soluble and free CoA in the liver of tumor-bearing animals, while selenomethionine caused the recovery of glutathione peroxidase levels in the liver, which was significantly diminished under Dx treatment. Both compounds decreased glutathione level in the liver, which was considerably induced by Dx.ConclusionsAntioxidants selenomethionine and D-pantethine partially reversed the negative side effects of Dx in NK/Ly lymphoma-bearing mice and significantly increased the therapeutic efficiency of this drug in tumor treatment.

Increased antitumor efficiency and reduced negative side effects in laboratory mice of 4-thiazolidinone derivatives in complexes with PEG-containing polymeric nanocarrier

“…NK/Ly lymphoma growth induced leukocytosis in the tumor-bearing mice that was well seen on the 21 st day after tumor inoculation. All agents used in this study -Les-3833 and Les-3288 compounds and doxorubicin (positive control) -significantly decreased tumorinduced leukocytosis, and a similar character of action was characteristic for segmented nuclei leukocytes and ring-shaped nuclei leukocytes as indicators of tissues damage [21,22]. However, tumor growth was shown to decrease significantly the number of small lymphocytes which provide protection against the action of antigens and toxic agents.…”

Tissue-protective activity of selenomethionine and D-panthetine in B16 melanoma-bearing mice under doxorubicin treatment is not connected with their ROS scavenging potential

“…We conducted studies using mice with NK/Ly lymphoma and showed that these dietary supplements, besides lowering the myelotoxicity of Dx, also lead to a boost of survival time of tumor-bearing animals (11). One of the aims of present study was to verify those data using more aggressive solid tumor model – murine B16 melanoma.…”

Antioxidants selenomethionine and D-pantethine differentially affect doxorubicin’s action on glutathione system in human leukemia cells varying in their resistance to chemotherapy in vitro

“…Нещодавно встановлено, що антиоксиданти (селенометіонін -SeMet і D-пантетин -D-Pt) проявляють нефро-, мієло-та гепатопротекторну активність щодо мишей-пухлиноносіїв, лікованих традиційним протипухлинним препаратом доксорубіцином (Dx). Крім того, ці антиоксиданти пригнічують цитотоксичний ефект Dx щодо чутливих до хіміотерапії пухлинних клітин і посилюють ефект препарату щодо певних стійких до хіміотерапії пухлинних клітинних ліній (HL-60/vinc, HL-60/adr), тоді як для інших резистентних клітинних ліній (HCT-116/Bax(−/−), HCT-116/p53) такий феномен ми не спостерігали [14][15][16][17].…”

“…It was found that antioxidant supplements possess nephro-, myelo-and hepatoprotective activity toward doxorubicin (Dx) action on the organism of tumor-bearing mice. Also, these antioxidants partially sensitized drugresistant tumor cells toward cytotoxic action of the doxorubicin (Dx) [15][16][17]. However, the molecular mechanisms underlying such effects of selenomethionine and D-pantethine remain unexplored.…”