Cytotoxic effect of Iranian vipera lebetina snake venom on HUVEC cells

Envenomation by heamotoxic snakes constituted a critical health occurrence in the world. Bleeding is the most sever consequence following snake bite with viperid and crothalid snakes. It is believed that the degradation of vascular membrane caused hemorrhage; in contrast, some suggested that direct cytotoxicity has role in endothelial cell disturbances. This study was carried out to evaluate the direct toxicity effect of V. lebetina crude venom on Human Umbilical Vein Endothelial Cells [HUVECs]. The effect of V. lebetina snake venom on HUVECs growth inhibition was determined by MTT assay and neutral red uptake assay. The integrity of cell membrane through LDH release was measured with the Cytotoxicity Detection Kit. Morphological changes of endothelial cells were also evaluated using a phase contrast microscope. In MTT assay, crude venom showed a cytotoxic effect on endothelial cells which was confirmed by the effect observed with neutral red assay. Also, crude venom caused changes in the integrity of cell membrane by LDH release. The morphological alterations enhanced in high concentration results in total cells number reduced. V. lebetina venom showed potential direct cytotoxic effects on human endothelial cells in a manner of concentration-dependent inhibition

Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage

Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system. The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study, thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin [30 mg/kg on the first day and 30 mg/kg on the following days], group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal [IP] injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde [MDA] and glutathione [GSH]. Each data point represents mean ñ standard error on the mean [SEM] of at least eight animals per group. A one-way analysis of variance [ANOVA] was performed to compare different groups, followed by Tukey's multiple comparison tests [p<0.05]. The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin [30 mg/kg] were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation

Toxicity of arsenic [III] on isolated liver mitochondria: a new mechanistic approach

Arsenic exposure mainly through food and water has been shown to be associated with increased incidence of numerous cancers and non-cancer harmful health. It is also used in cancer chemotherapy and treatment of several cancer types due to its apoptogenic effects in the various cancer and normal cell lines. We have already reported that liver is the storage site and important target organ in As [III] toxicity and recently, it has been suggested that hepatic toxicity of arsenic could be resulted from impairment of the liver mitochondria. In this study, interaction of As [III] with freshly isolated rat mitochondria was investigated. We determined different mitochondrial toxicity factors as well as mitochondrial sources of ROS formation using specific substrates and inhibitors following addition of As [III] to the mitochondria. Our results showed that arsenic [III] increased mitochondrial ROS formation, lipid peroxidation and mitochondrial membrane potential collapse, cytochrome c release and mitochondrial swelling in a concentration dependent manner. Addition of As [III] in to the isolated mitochondria, inhibited complexes I and II leading to disruption of mitochondrial electron transfer chain, decreased mitochondrial ATP content and ROS formation

Radioprotective effect of melatonin in reducing oxidative stress in rat lenses

Ocular morbidity is widely observed when radiotherapy includes the orbit. Oxidative stress generated by irradiation is responsible for this complication. In different studies, it has been shown that melatonin has antioxidative properties and a radioprotective role. The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury in rats' lenses after total cranial irradiation. Thirty-six adult female Sprague-Dawley rats were divided into six groups. Group I was the control group, group II only received total cranial gamma irradiation of 5 Gy, group III was exposed as the second group but at the dose of 8 Gy, group IV received 30 mg/kg melatonin 30 minutes prior to radiation plus total cranial irradiation of 5 Gy plus 5 mg/kg melatonin daily through intraperitoneal injection for ten days after irradiation, group V was treated similar to the fourth group, i. e. received irradiation plus melatonin, but at the dose of 8 Gy, and group VI only received melatonin [30 mg/kg on the first day and 5 mg/kg on the following days]. Ten days after irradiation, all rats were sacrificed and their eyes were enucleated to measure the biochemical parameters i. e. malondialdehyde [MDA] and glutathione [GSH]. The levels of MDA in rat lenses increased and the levels of glutathione in lenses decreased after gamma ray irradiation but these parameters were still within normal limits in rats that received melatonin. It could be concluded that melatonin is useful in preventing radiation-induced oxidative injury due to its antioxidative and free radical scavenging properties

Effect of captopril on TNF- alpha and IL-10 in the livers of bile duct ligated rats

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

Evaluation of melatonin for prevention of radiation myelopathy in irradiated cervical spinal cord

Radiation myelopathy [RM] is known as a serious complication of head and neck radiation therapy. Furthermore, the radioprotective roles of melatonin have been investigated on different tissues. The aim of this study was to assess the radio protective effects of melatonin on biochemical, histopathological and clinical manifestations of RM in the rat cervical spinal cord. Four groups of rats were investigated as follows: The control group was treated with vehicle. The second group [melatonin only] was intraperitoneally injected with 100 mg/kg melatonin. The third group's [radiation] cervical spinal cord area was irradiated with 22 Gy cobalt-60 gamma-rays. The fourth group [melatonin plus irradiation] received 100 mg/kg melatonin intraperitoneally, and after 30 minutes their spinal cord area was irradiated with 22 Gy gamma radiation. Five animals from each group were randomly selected. 72 hours, 8 and 22 weeks after irradiation for analysis of malondialdehyde [MDA] and glutathione [GSH] levels, and underwent histopathological studies. The MDA levels in the irradiation group were significantly higher than in the control group [p < 0.001]. Furthermore, the GSH levels in this group were significantly lower than that of those in the control group [p < 0.001]. Administration of melatonin markedly reduced MDA [p < 0.001] and increased GSH [p < 0.05] levels in this group. Demyelination and clinical signs of myelopathy were decreased in the melatonin plus irradiation group in comparison to the irradiated group. Our study confirms the radioprotective effects of melatonin at early stages of biochemical, as well as late histological and clinical changes in the spinal cord

T2-toxin hepatotoxicity in the in situ rat liver model

T-2 toxin, a trichothecene mycotoxin, is considered to be one of the most toxic compounds that are produced by molds, particularly the Fusarium species. Fusarium species have been recognized as a great agricultural problem. They occur worldwide on a variety of plant hosts and cereal grains. The aim of this study was to investigate T-2 toxin-induced liver injury using in situ perfused rat liver. The in situ perfused rat liver [IPRL] was chosen because it permits studies of liver function in a system that resembles normal physiology. Elevation of aminotransferase activities have shown to be a good indicator of hepatocellular damage. In addition, glutathione levels have also shown to be an indicator of liver damage through lipid peroxidation. Male Sprague-Dawley rats [6-8 weeks] weighing 250-300 g were used in this study. They were randomly divided into 5 groups of 3-4 rats per cage. In group 1, liver was perfused by Krebs-Henseleit buffer alone [Control]. Groups 2-5 received different concentration of T-2 toxin [4, 9, 21, 43 [rho]mol/L] in Krebs-Henseleit buffer and biochemical changes in the liver were examined within 2 h. There was a significant increase in both ALT and AST activity in all dose levels compared with the control group [p<0.01 and p<0.05]. T-2 toxin treatment enhanced lipid peroxidation in the liver, as indicated by the increased MDA content in liver homogenates. The MDA level was maximal 2 h after the T-2 toxin challenge [p<0.01 and p<0.05]. The results also show that T-2 toxin causes an increase in lipid peroxidation while causing a decrease in glutathione [GSH] content in bile secretion [p<0.01]. This result suggests that both lipid peroxidation and glutathione [GSH] depletion play a role in T-2 toxin liver induced damages