hepatoprotective effects of aquatic extract of Levisticum officinale against paraquat hepatocyte toxicity

Paraquat is extensively used as a strong nitrogen-based herbicide for controlling weeds in agriculture. This herbicide is extremely toxic to humans and induces multiorgan failure due to accumulation in the cells. So far, many instances of fatal poisoning have been reported. Paraquat is metabolized primarily in the liver. Accordingly, the effects of aquatic Levisticum officinale extract on biochemical factors and oxidative status were evaluated in hepatocytes exposed to paraquat in this study. The results showed that paraquat-induced hepatocyte destruction is mediated by reactive oxygen species [ROS] production. The aquatic extracts of Levisticum officinale [100, 200, and 300 micro g/mL] could prevent lipid peroxidation and reduction in the potential of mitochondrial membranes [P<0.05]. The antioxidants, ROS scavengers [mannitol, dimethyl sulfoxide, and alpha-tocopherol], and mitochondrial permeability transition pore-sealing agent [carnitine] inhibited the effects of paraquat. The pore-sealing compound inhibited hepatotoxicity, indicating that paraquat induces cell death via mitochondrial pathways. Hepatic cell death due to paraquat could be prevented by hepatocyte pretreatment with aquatic Levisticum officinale extracts, antioxidants, and ROS scavengers; therefore, oxidative stress might directly reduce the mitochondrial membrane potential. In conclusion, paraquat hepatotoxicity may be associated with oxidative stress and maintained by the disruption of mitochondrial membrane potential. Levisticum officinale aquatic extract, presumably due to its strong antioxidant properties, could protect against the destructive effects of paraquat on rat hepatocytes

Cytoprotective effects of hydrophilic and lipophilic extracts of pistacia vera against oxidative versus carbonyl stress in rat hepatocytes

This study was conducted to evaluate the cytoprotection of various extracts and bioactive compounds found in Pistacia vera againts cytotoxicity, ROS formation, lipid peroxidation, protein carbonylation, mitochondrial and lysosomal membrane damages in cell toxicity models of diabetes related carbonyl [glyoxal] and oxidative stress [hydroperoxide]. Methanol, water and ethyl acetate were used to prepare crude pistachios extracts, which were then used to screen for in-vitro cytoprotection of freshly isolated rat hepatocytes against these toxins. The order of protection by Pistacia vera extracts against both hydroperoxide induced oxidative stress [ROS formation] and glyoxal induced protein carbonylation was: pistachio methanolic extract > pistachio water extract, gallic acid, catechin > alpha-tochoferol and pistachio ethyl acetate extract. Finally due to higher protection achieved by methanolic extract even compared to sole pretreatment of gallic acid, catechin or alpha-tochoferol, we suggest that cytoprotection depends on the variety of polar and non-polar compounds found in methanolic extract, it is likely that multiple cytoprotective mechanisms are acting against oxidative and carbonyl induced cytotoxicity. To our knowledge, we are the first to report the cytoprotective activity of Pistacia vera extracts against oxidative and carbonyl stress seen in type 2 diabetes hepatocytes model

Ichthyotoxic cochlodinium polykrikoides induces mitochondrial mediated oxidative stress and apoptosis in rat liver hepatocytes

In this research, we investigated the cytotoxic mechanisms of CochlodiniumpolykrikoidescQ/ lysate on isolated rat liver hepatocytes.This micro algae is responsible for a severe and widespread harmful algal bloom in the Persian Gulf and Gulf of Oman [2008-2009]. Isolated hepatocytes were obtained by collagenase perfiision of Sprague-Dawley rat liver.According to our results, incubation of algal lysate with isolated rat hepatocytescaused hepatocyte membrane lysis, reactive oxygen species [ROS] formation, glutathione depletion, collapse of mitochondrial membrane potential,ATP depletion and increase in ADP/ATP ratio, cytochrome c release in to the hepatocyte cytosol,activation of caspase-3 [final mediator of apoptosis] and appearance of apoptosis phenotype. On the other hand, pre-treatment of antioxidants [a-tocopherol succinate and BHT], radical scavengers [mannitol and DMSO], mitochondrial permeability transition [MPT] pore sealing agents [cyclosporine A, carnitine and trifluoperazine], NADPH P450 reductase inhibitor [Diphenyliodonium chloride], CYP2E1 inhibitors [Phenylimidazole and 4-Methylpyrazole] and ATP generators [L-glutamine, Fructose and Xylitol]inhibitedcaspase-3 activation and cell death in algal lysate treated hepatocytes.Our data also confirmed that algal lysate activates apoptosis signaling via oxidative stress and mitochondrial pathway. Thus, ROS formation caused by the lysate exposure could directly be involved in mitochondrial MPT pore opening and activation of caspase-3 leading to C.polykrikoides lysateinduced apoptosis on rat hepatocytes. These findings contribute to a better understanding QfC.polykrikoides-toxic effects on mammalian liver cells