Cisplatin, a
platinum chelate with potent antitumor activity against
cancers of the testis, ovary, urinary bladder, prostate, and head and neck, has adverse effects on the kidney, bone marrow, and digestive organs, and its use is particularly limited by nephropathy as a side effect. In the present study, safflower seed extract was administered to a mouse model of
cisplatin-induced
acute renal failure to investigate its activity.
Cisplatin (20[Formula: see text]mg/kg
body weight) was administered by
intraperitoneal injection to mice that had received oral safflower seed extract (100 or 200[Formula: see text]mg/kg
body weight per day) for the preceding 2 days. Three days after the
cisplatin injection, serum and renal biochemical factors; oxidative stress,
inflammation, and apoptosis-related
protein expression; and histological findings were evaluated.
Cisplatin-treated control mice showed
body-weight, food intake and water intake loss, and increased kidney weight, whereas the administration of safflower seed extract attenuated these effects ([Formula: see text], [Formula: see text]). Moreover, safflower seed extract significantly decreased the renal functional parameters
urea nitrogen and
creatinine in the serum ([Formula: see text] and [Formula: see text], respectively). Safflower seed extract also significantly reduced the enhanced levels of
reactive oxygen species in the kidney observed following
cisplatin treatment, with significance. The expression of
proteins related to the
anti-oxidant defense system in the kidney was down-regulated following
cisplatin treatment, but safflower seed extract significantly up-regulated the expression of the
anti-oxidant enzyme catalase. Furthermore, safflower seed extract reduced the overexpression of phosphor (p)-p38,
nuclear factor-kappa B p65,
cyclooxygenase-2,
inducible nitric oxide synthase, ATR, p-p53, Bax, and
caspase 3 proteins, and mice treated with safflower seed extract exhibited less renal histological damage. These results provide important evidence that safflower seed extract exerts a pleiotropic effect on several oxidative stress- and apoptosis-related parameters and has a renoprotective effect in
cisplatin-treated mice.