ABSTRACT
Sunitinib (SUN) is a chemotherapeutic agent clinically approved for treatment of metastatic renal carcinoma. Despite its remarkable benefits, various renal toxicities have been reported that limit its clinical uses. Oleuropein (OLE) is the main polyphenolic constituent of olive tree and mediates the majority of its valuable pharmacological activities. The current study examined the probable renoprotective effects of OLE against SUN-induced nephrotoxicity. Adult male albino rats were co-treated by SUN (25 mg/kg, 3 times/week, PO) with either a drug vehicle or OLE (60 mg/kg/day, daily, PO) for four weeks. A control group comprising of age-matched rats was used. Four weeks later, blood specimens were collected to assess kidney functions. Kidneys were harvested for biochemical and histopathological analyses. Administration of SUN induced kidney dysfunction, along with marked rises in endothelin-1 (ET-1) and monocyte chemotactic protein-1 (MCP-1) levels in renal tissues. Histological abnormalities were also detected in kidneys of SUN-treated rats including glomerular and tubular interstitial congestion along with interstitial fibrosis. On molecular levels, there was a decline in renal SIRT6 expression along with significant up-regulation of Notch-1, NLRP-3, interleukin -1ß (IL-1ß) and cleaved caspsase-3. All these changes were almost alleviated by OLE co-treatment. These findings suggest the implication of SIRT6/Notch-1/NLRP3/IL-1ß axis in the pathogenesis of SUN-induced nephrotoxicity and highlight OLE as a prospective renoprotective agent during SUN chemotherapy to halt its renal toxicity likely through promotion of SIRT6 and suppression of Notch-1/NLRP3/IL-1ß signaling pathway.
ABSTRACT
OBJECTIVE: We aimed to compare maternal and neonatal outcomes of spontaneous term labor among primigravidae who were monitored by the novel labor scale versus the World Health Organization (WHO) partograph. STUDY DESIGN: A single center, double-blinded randomized trial had been conducted between July 2015 and June 2016. Nulliparous women in spontaneous labor with singleton term pregnancies were randomized to either labor scale or the WHO partograph for management of labor. Primary outcome was successful vaginal delivery. Secondary outcome included low APGAR scores, birth injuries, postpartum hemorrhage, and infection. RESULTS: One hundred ten patients were randomized (55 in each arm). Women managed with labor scale had significantly lower rate of cesarean deliveries than women managed with the partograph arm (3.6% versus 18.2%, P=0.03). There was a significant reduction in the rate and duration of oxytocin administration for augmentation of labor (21.8% versus 69.1%, P < 0.0001) and a significant increase in average 1-minute APGAR score in the labor scale group. CONCLUSION: Labor monitoring with the labor scale is associated with lower rate of cesarean section, less and shorter use of oxytocin for augmentation of labor. Monitoring of labor progress starting at 5 cm or more is also associated with lower rate of cesarean delivery.
