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


METHODS
The 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.


RESULTS
D-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.


CONCLUSIONS
Antioxidants 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.
Rostyslav R. Panchuk, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov Street 14/16, 79005, Lviv, Ukraine, rpanchuk@ukr.net.
Rostyslav R
RR
Panchuk
Nadia R
NR
Skorokhyd
Yuliya S
YS
Kozak
Liliya V
LV
Lehka
Vira V
VV
Chumak
Sofya N
SN
Omelyanchik
Valery A
VA
Gurinovich
Andrey G
AG
Moiseenok
Rostyslav S
RS
Stoika
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010204:Pantetheine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012645:Selenomethionine / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000975:Antioxidants; D010204:Pantetheine; C005425:pantethine; D004317:Doxorubicin; D012645:Selenomethionine; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione