Nephrotoxicity is one of the most important complications of
cisplatin, a potent chemotherapeutic agent used in the treatment of various
malignancies.
5-HT3 antagonists are widely used to counteract
chemotherapy-induced
emesis and new studies reveal that they poses notable anti-inflammatory properties. In current study, we investigated the effects of
5-HT3 antagonists on
cisplatin induced nephrotoxicity in mice. To identify the underlying mechanism of renal protection by
tropisetron, we investigated the probable involvement of
alpha7 nicotinic acetylcholine receptor (α7nAChR). A single injection of
cisplatin (20mg/kg; i.p) induced nephrotoxicity,
5-HT3 antagonists (
tropisetron,
granisetron and
ondansetron,) were given twice daily for 3 day (3mg/kg; i.p). Finally animals were euthanized and blood sample was collected to measure
urea and creatinin level. Also kidneys were removed for histopathological examination and biochemical measurements including
glutathione (GSH),
malondialdehyde (MDA),
superoxide dismutase (SOD) activity,
inducible nitric oxide synthase (iNOS) expression and inflammatory
cytokines.
Tropisetron decreased the expression of inflammatory molecules including
tumor necrosis factor-alpha (TNF-α),
interleukin-1 beta (IL-1β) and iNOS and improved histopathological damage and renal dysfunction. However other
5-HT3 antagonists,
granisetron or
ondansetron do not have any elicit effects on
biochemical markers and histological damages. Since
methyllycaconitine, antagonist of α7nAChR, was unable to reverse the beneficial effect of
tropisetron, we concluded that this effect of
tropisetron is not mediated by α7nAChR.Our results showed that
tropisetron treatment markedly ameliorated the experimental
cisplatin induced-nephrotoxicity and this effect might be
5-HT3 receptor and α7nAChR independent.