J Korean Diabetes Assoc.  2002 Feb;26(1):57-63.

Effects of Gutathione on Cyclosporine A-induced Cyotoxicity in Cultured Rat Insulinoma (RIN5mF) Cells

• Choi DH
• Lee BR
• Jang DY
• Kim JO
• Kim BS
• Chung KY
• Lim TY
• Shin BC
• Bae HY

Abstract

BACKGROUND: Cyclosporin A (CsA) is a immunosuppressive agent that is most widely used in organ transplanted patients to prevent immunorejection, However, it has some side effects, including diabetes mellitus, nephrotoxicity and hypertension. The mechanism of CsA cytotoxicity is unclear but it has been suggested that reactive oxygen species are involved in the cytotoxic reactions. The purpose of this study was to determine the effects of glutathione, as a physiological antioxidant on CsA induced beta-cell toxicity.
METHODS
Rat insulinoma (RINm5F) cells were incubated with culture media (RPMI1640) in the presence of CsA and/or buthionine sulfoximine (BSO), which is an inhibitor of r-glutamyl cysteine synthetase, and reduced glutathione. The viable cells were examined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and was determined by a spectrophotometer at a wavelength of 570 nm.
RESULTS
Incubating the RINm5F cells with CsA resulted in a decrease in cell viability with increasing dose. This deceased cells viability, induced by CsA was potentiated by BSO treatment. The CsA and BSO induced cells toxicity was reduced significantly by the reduced glutathione.
CONCLUSION
The results suggest that pancreatic beta-cell may be injured by CsA and glutathione may have some role in cytotoxicity.

Keyword

Cyclosporine A; RIN5mF cell; Glutathione

MeSH Terms

Animals
Buthionine Sulfoximine
Cell Survival
Culture Media
Cyclosporine*
Cysteine
Diabetes Mellitus
Glutathione
Humans
Hypertension
Insulinoma*
Ligases
Rats*
Reactive Oxygen Species
Buthionine Sulfoximine
Culture Media
Cyclosporine
Cysteine
Glutathione
Ligases
Reactive Oxygen Species