Breast cancer is the current leading cause of cancer death in females worldwide. Although current chemotherapeutic drugs effectively reduce the progression of breast cancer, most of these drugs have many unwanted side effects. Salvianolic acid B (Sal-B) is a bioactive compound isolated from the root of Danshen Radix with potent antioxidant and anti-inflammatory properties. Since free radicals play a key role in the initiation and progression of tumor cells growth and enhance their metastatic potential, the current study was designed to investigate the antitumor activity of Sal-B and compare it with the antitumor activity of the traditional anticancer drug, cisplatin. In vitro, Sal-B decreased the human breast cancer adenocarcinoma (MCF-7) cells proliferation in a concentration and time dependent manner. In vivo and similar to cisplatin treatment, Sal-B significantly reduced tumor volume and increased the median survival when compared to tumor positive control mice group injected with Ehrlich solid carcinoma cell line (ESC). Sal-B decreased plasma level of malondialdehyde as a marker of oxidative stress and increased plasma level of reduced glutathione (GSH) as a marker of antioxidant defense when compared to control ESC injected mice. Either Sal-B or cisplatin treatment decreased tumor tissue levels of tumor necrosis factor (TNF-α), matrix metalloproteinase-8 (MMP-8), and Cyclin D1 in ESC treated mice. Contrary to cisplatin treatment, Sal-B did not decrease tumor tissue Ki-67 protein in ESC injected mice. Immunohistochemical analysis revealed that Sal-B or cisplatin treatment increased the expression of the apoptotic markers caspase-3 and P53. Although Sal-B or cisplatin significantly reduced the expression of the angiogenic factor vascular endothelial growth factor (VEGF) in ESC injected mice, only Sal-B reduced expression level of COX-2 in ESC injected mice. Our data suggest that Sal-B exhibits antitumor features against breast cancer cells possibly via enhancing apoptosis and reducing oxidative stress, inflammation, and angiogenesis.

Although numerous clinical and experimental studies have clearly identified a sexual dimorphism in blood pressure control, the mechanism(s) underlying gender differences in blood pressure remain unclear. Over the past two decades, numerous laboratories have utilized the spontaneously hypertensive rats (SHR) as an experimental model of essential hypertension to increase our understanding of the mechanisms regulating blood pressure in males and females. Previous work by our group and others have implicated that differential regulation of adrenergic receptors, the renin–angiotensin system, oxidative stress, nitric oxide bioavailability and immune cells contribute to sex differences in blood pressure control in SHR. The purpose of this review is to summarize previous findings to date regarding the mechanisms of blood pressure control in male versus female SHR.

Hepatic injury is a hallmark adverse reaction to Valproate (VPA), a common used drug in the management of numerous CNS disorders, including epilepsy. DHA has a myriad of health benefits, including renal- and hepato-protective effects. Unfortunately, however, the underpinnings of such liver-pertinent VPA- and DHA-actions remain largely undefined. Accordingly, this study attempted to unveil the cellular and molecular triggers whereby VPA evokes, while DHA abates, hepatotoxicity. We evaluated activity and/or expression of cellular markers of oxidative stress, inflammation, and apoptosis in rat liver, following treatment with VPA (500 mg/kg/day) with and without concurrent treatment with DHA (250 mg/kg/day) for two weeks. VPA promoted hepatic oxidative stress as evidenced by enhancing activity/expression of NADPH-oxidase and its subunits, a ROS-generator, and by accumulation of lipid-peroxides. Moreover, VPA enhanced hepatic phosphorylation/activation of mitogen-activated protein kinase (MAPK), and expression of cyclooxygenase-2(COX-2), as proinflammatory signals. Besides, VPA promoted hepatocellular apoptosis, as attested by enhanced expression of cleaved caspase-9 and increased number of TUNEL-positive hepatocytes. Lastly, VPA upregulated levels of hypoxia-inducible factor-1-alpha (HIF-1α), a multifaceted modulator of hepatocytic biology, and activity of its downstream antioxidant enzyme heme-oxygenase-1(HO-1). These changes were significantly blunted by co-administration of DHA. Our findings demonstrate that VPA activated NADPH-oxidase and HIF-1α to induce oxidative-stress and hypoxia as initiators of hepatic injury. These changes were further aggravated by up-regulation of inflammatory (MAPK and COX-2) and apoptotic cascades, but could be partly lessened by HO-1 activation. Concurrent administration of DHA mitigated all VPA-induced anomalies.

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats. Rats (11–14 wk old) were randomized to one of the following four groups: control, norepinephrine (NE) infusion, angiotensin II infusion, or the NOS inhibitor N^ω-nitro-l-arginine methyl ester (l-NAME) in drinking water. BP was measured via tail cuff. After 2 wk of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in norepinephrine-and angiotensin II-treated rats were associated with increases in renal Tregs versus control. In contrast, l-NAME treatment decreased Tregs compared with all groups. l-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups, and there was no histological evidence of glomerular or tubular injury. This study provides insights into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.