Renoprotection by alpha-Mangostin is

related to the attenuation in renal

oxidative/nitrosative stress induced by
cisplatin nephrotoxicity.
Prez-Rojas JM, Cruz C, Garca-Lpez P, Snchez-Gonzlez DJ, Martnez-Martnez CM,
Ceballos G, Espinosa M, Melndez-Zajgla J, Pedraza-Chaverri J.

Source
Facultad de Qumica, Departamento de Biologa, Universidad Nacional Autnoma de
Mxico, Edificio F, Mexico City, Mexico.

Abstract
Cisplatin (CDDP) is a chemotherapeutic agent that produces nephrotoxicity associated with
oxidative/nitrosative stress. alpha-Mangostin (alpha-M) is a xanthone extracted from
mangosteen with antioxidant and anti-inflammatory properties. The purpose of this study was
to evaluate the renoprotective effect of alpha-M on the CDDP-induced nephrotoxicity. alphaM was administered (12.5 mg/kg/day, i.g.) for 10 days (7 days before and 3 days after CDDP
injection). On day 7, rats were treated with a single injection of CDDP (7.5 mg/Kg, i.p.); 3
days after the rats were killed. alpha-M attenuated renal dysfunction, structural damage,
oxidative/nitrosative stress, decrease in catalase expression and increase in mRNA levels of
tumour necrosis factor alpha and transforming growth factor beta. In conclusion the
renoprotective effect of alpha-M on CDDP-induced nephrotoxicity was associated with the
attenuation in oxidative/nitrosative stress and inflammatory and fibrotic markers and
preservation of catalase activity.
http://www.ncbi.nlm.nih.gov/pubmed/19863372

The alpha-mangostin prevention on

cisplatin-induced apoptotic death in LLCPK1 cells is associated to an inhibition of
ROS production and p53 induction.
Snchez-Prez Y, Morales-Brcenas R, Garca-Cuellar CM, Lpez-Marure R, CalderonOliver M, Pedraza-Chaverri J, Chirino YI.

Source
Subdireccin de Investigacin Bsica, Instituto Nacional de Cancerologa, San Fernando No.
22, Tlalpan, 14080 Mexico, DF, Mexico.

Abstract
Cisplatin (CDDP) is a widely useful chemotherapeutic agent for the treatment of tumors
including lung, ovary and testis. Acute renal injury, however, is the main side effect observed
after CDDP treatment. This side effect is related to the apoptotic death in proximal tubular
cells in the kidney and p53 protein has a central role in this process. On the other hand, alphamangostin (alpha-M), a xanthone derived from the pericarp of mangosteen, exerts a
renoprotective effect against cisplatin-induced renal damage in rats. The aim of this study
was to evaluate whether alpha-M protects proximal tubule renal epithelial cells (LLC-PK1)
from CDDP-induced apoptotic death. Cells were co-incubated with 5 microM alpha-M and
100 microM CDDP for 24h. It was found that alpha-M attenuated the following alterations:
the apoptotic cell death, the increase in reactive oxygen species (ROS), the glutathione
depletion and the increase in p53 expression induced by CDDP. In conclusion, the preventive
effect of alpha-M on CDDP-induced apoptotic death is associated to the inhibition of p53
expression and ROS generation.
http://www.ncbi.nlm.nih.gov/pubmed/20603111