Cisplatin is a highly cytotoxic drug used for the treatment of head, neck, and soft tissue cancers; however, it has nephrotoxic effects that can lead to acute kidney injury. Protocatechuic acid (PCA) is a natural widely available antioxidant found in many fruits such as kiwi, mango, and berries. We have recently shown that PCA reduced renal injury in a mouse model of unilateral ureteral obstruction. The current study aims to investigate the protective effects of PCA in Cisplatin-induced inflammation in vitro in Boston University Mouse Proximal Tubular (BUMPT) cells. BUMPT cells were cultured in complete DMEM. Confluent BUMPT cells were then treated with 20 μM Cisplatin ± PCA 50 or 100 μM for 24 h. PCA treatment showed a dose-depending increase in % cell viability in Cisplatin-treated BUMPT cells. PCA treatment also dose-dependently decreased Cisplatin-induced increases in oxidative stress (ROS and TBARS), inflammation (p-NF-κB and IL-6), and apoptosis (cleaved caspase-3 and % of TUNEL⁺ cells) compared to Cisplatin-only treatment. The reduction in oxidative stress, inflammation, and apoptosis with PCA treatment in Cisplatin-treated BUMPT cells was associated with decreases in tubular physical barrier resistance and the expression of the tight junction protein zonula occludens-1 (ZO-1) when compared to BUMPT cells treated with Cisplatin alone. The current findings suggest that PCA treatment improves tubular barrier function in Cisplatin-treated BUMPT cells via reductions in oxidative stress, inflammation, and apoptosis.

Nitric oxide (NO) contributes to blood pressure (BP) regulation via its vasodilatory and anti‐inflammatory properties. We and others previously reported sex differences in BP in normotensive and hypertensive rat models where females have lower BP than age‐matched males. As females are known to have greater NO bioavailability than age‐matched males, the current study was designed to test the hypothesis that anesthetized female normotensive Wistar Kyoto rats (WKY) are more responsive to acute NOS inhibition‐induced increases in BP compared to male WKY. Twelve‐week‐old male and female WKY were randomized to infusion of the nonspecific NOS inhibitor N^G‐nitro‐L‐arginine methyl ester (L‐NAME, 1 mg/kg/min) or selective NOS1 inhibition with vinyl‐L‐NIO (VNIO, 0.5 mg/kg/min) for 60 min. Mean arterial BP, glomerular filtration rate (GFR), urine volume, and electrolyte excretion were assessed before, and during L‐NAME or VNIO infusion. L‐NAME and VNIO significantly increased BP in both sexes; however, the increase in BP with L‐NAME infusion was greater in females versus males compared to baseline BP values. Acute infusion of neither L‐NAME nor VNIO for 60 min altered GFR in either sex. However, urine volume, sodium, chloride and potassium excretion levels increased comparably in male and female WKY with L‐NAME and VNIO infusion. Our findings suggest sex differences in BP responses to acute non‐isoform‐specific NOS inhibition in WKY, with females being more responsive to L‐NAME‐induced elevations in BP relative to male WKY. However, sex differences in the BP response did not coincide with sex differences in renal hemodynamic responses to acute NOS inhibition.