ABSTRACT
Background@#Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known antiinflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. @*Methods@#Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. @*Results@#NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. @*Conclusions@#These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.
ABSTRACT
In the recent years, the role of LOX enzymes in the origin of neoplastic diseases such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized and the cytotoxicity of the members of this series was assessed using MTT protocol. Enzyme inhibitory activity of the prepared compounds was also tested against 15-lipoxygenase-1 as a novel target for the discovery of anticancer drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were compared with doxorubicin. Overall, nitro containing derivatives exerted a higher cytotoxic activity against PC3 cell line and methoxylated derivatives showed an acceptable activity against SKNMC cell line. Methoxylated derivatives were also the most potent enzyme inhibitors especially at position ortho of the phenyl residue
ABSTRACT
The renin-angiotensin system has an important role in hepatic inflammation and fibrosis. Renin-angiotensin system blockade by angiotensin-converting enzyme [ACE] inhibitors provides some protective effects against hepatic fibrogenesis. Captopril as an ACE inhibitor can decrease inflammatory mediators and attenuate hepatic fibrosis in the livers of bile duct ligated [BDL] rats. The present study was conducted to investigate the effects of captopril on cytokine production in hepatic fibrosis induced by a bile duct ligation model in rats. Male rats were divided into four groups including; control, sham operated, BDL, and BDL plus captopril [10 mg/kg/day, orally]. After 28 days of treatment, the livers were removed for cytokine analysis. Hepatic interleukin [IL]-10 and tumor necrosis factor [TNF]- alpha levels were measured. Captopril treatment decreased the hepatic content of the proinflammatory cytokine TNF- alpha and increased the anti-inflammatory cytokine IL-10. The present study suggests that the protective effect of captopril on hepatic fibrosis is likely to be mediated by cytokine production