Objective:To explore the cytotoxicity effects of Caspian cobra (Naja oxiana or N.oxiana) venom on hepatocytes and mitochondria obtained from the liver of HCC rats.Methods:In this study,HCC was induced by diethylnitrosamine (DEN),as an initiator,and 2-acetylaminofluorene (2-AAF),as a promoter.Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effect of N.oxiana venom were isolated and mitochondria and cellular parameters related to apoptosis signaling were then determined.Results:Our results showed a raise in mitochondrial reactive oxygen species (ROS)level,swelling in mitochondria,mitochondrial membrane potential (△ψm) collapse and release of cytochrome c after exposure of mitochondria only isolated from the HCC group with the crude venom of the N.oxiana (12.5,25,and 50 μg/mL).This crude venom also induced caspase-3 activation (P ＜ 0.001) in the hepatocytes obtained only from the HCC rat liver.Conclusions:Based on the over all results,we suggested that N.oxiana may be considered as a promising complementary therapeutic agent for the treatment of HCC.

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.

Objective To explore the cytotoxicity effects of Caspian cobra (Naja oxiana or N. oxiana) venom on hepatocytes and mitochondria obtained from the liver of HCC rats. Methods In this study, HCC was induced by diethylnitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effect of N. oxiana venom were isolated and mitochondria and cellular parameters related to apoptosis signaling were then determined. Results Our results showed a raise in mitochondrial reactive oxygen species (ROS) level, swelling in mitochondria, mitochondrial membrane potential (Δψm) collapse and release of cytochrome c after exposure of mitochondria only isolated from the HCC group with the crude venom of the N. oxiana (12.5, 25, and 50 μg/mL). This crude venom also induced caspase-3 activation (P < 0.001) in the hepatocytes obtained only from the HCC rat liver. Conclusions Based on the over all results, we suggested that N. oxiana may be considered as a promising complementary therapeutic agent for the treatment of HCC.