Cisplatin is a classic chemotherapeutic agent widely used to treat different types of
cancers including ovarian, head and neck, testicular and uterine cervical
carcinomas. However,
cisplatin induces
acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of
protocatechuic aldehyde (PA) in vitro in
cisplatin-treated tubular epithelial cells and in vivo in
cisplatin nephropathy. PA is a monomer of
Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented
cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both
mRNA and
protein levels. Moreover, PA reduced renal
inflammation by suppressing oxidative stress and programmed cell death in response to
cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH
oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on
cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in
cisplatin-induced
acute kidney injury. Collectively, our data indicate that PA blocks
cisplatin-induced
acute kidney injury by suppressing Nox-mediated oxidative stress and renal
inflammation without compromising anti-
tumor activity of
cisplatin. These findings suggest that PA and its derivatives may serve as potential
protective agents for
cancer patients receiving
cisplatin treatment.