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Molecular mechanisms of cisplatin-induced nephrotoxicity: a balance on the knife
edge between renoprotection and tumor toxicity
#MMPMID30866950
Volarevic V
; Djokovic B
; Jankovic MG
; Harrell CR
; Fellabaum C
; Djonov V
; Arsenijevic N
J Biomed Sci
2019[Mar]; 26
(1
): 25
PMID30866950
show ga
BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most
effective chemotherapeutic agents. However, its clinical use is limited due to
the severe side effects, including nephrotoxicity and acute kidney injury (AKI)
which develop due to renal accumulation and biotransformation of CDDP. The
alleviation or prevention of CDDP-caused nephrotoxicity is currently accomplished
by hydration, magnesium supplementation or mannitol-induced forced diuresis which
is considered for high-dose CDDP-treated patients. However, mannitol treatment
causes over-diuresis and consequent dehydration in CDDP-treated patients,
indicating an urgent need for the clinical use of safe and efficacious
renoprotective drug as an additive therapy for high dose CDDP-treated patients.
MAIN BODY: In this review article we describe in detail signaling pathways
involved in CDDP-induced apoptosis of renal tubular cells, oxidative stress and
inflammatory response in injured kidneys in order to pave the way for the design
of new therapeutic approaches that can minimize CDDP-induced nephrotoxicity. Most
of these molecular pathways are, at the same time, crucially involved in
cytotoxic activity of CDDP against tumor cells and potential alterations in their
function might mitigate CDDP-induced anti-tumor effects. CONCLUSION: Despite the
fact that many molecules were designated as potential therapeutic targets for
renoprotection against CDDP, modulation of CDDP-induced nephrotoxicity still
represents a balance on the knife edge between renoprotection and tumor toxicity.
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