Vanadium as a trace element is considered essential for animals; however it has not yet been recognized as a micronutrient for humans. Most of the information on the biological effects of vanadium was related to metal's insulin-like, anti-hyperlipidemic and anticancer properties in low concentrations. According to the previous literature, mitochondria were proposed as an important target for vanadium cytotoxicity. In this study, the mitochondrial toxicity mechanisms of sodium metavanadate (vanadium V or V(5+)) were investigated in the isolated mitochondria obtained from rat liver by differential centrifugation and mitochondrial toxicity endpoints as well as mitochondrial sources of ROS formation were determined in both in vivo and in vitro using specific substrates and inhibitors. Single injection of V(5+) into Wistar rat (10, 20 and 40 mg kg(-1), i.p.) caused a significant increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Isolated mitochondria from the V(5+)-treated rat liver showed a marked elevation in oxidative stress parameters accompanied by mitochondrial membrane potential (MMP) collapse as compared to a control group. On the other hand, our in vitro results with isolated mitochondria showed that different concentrations of V(5+) (25-200 μM) induced significant (P < 0.05) progress in mitochondrial ROS formation, ATP depletion, GSH oxidation, mitochondrial outer membrane rupture, mitochondrial swelling and cytochrome c release before the mitochondrial potential collapse ensued. We also showed that the V(5+) interaction with respiratory complex III is the major source of V(5+)-induced ROS formation. In general, our in vivo and in vitro data strongly supported that the V(5+)-induced liver toxicity is a result of the metal disruptive effect on the mitochondrial respiratory complexes I, II and III which are the obvious causes of metal-induced ROS formation and ATP depletion in liver cells which leads to cell death signalling via MPT pore opening and cytochrome c release.

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Oxidative damage has been implicated in disorders associated with abnormal copper metabolism and also Cu(2+) overloading states. Besides, mitochondria are one of the most important targets for Cu(2+), an essential redox transition metal, induced hepatotoxicity. In this study, we aimed to investigate the mitochondrial toxicity mechanisms on isolated rat liver mitochondria. Rat liver mitochondria in both in vivo and in vitro experiments were obtained by differential ultracentrifugation and the isolated liver mitochondria were then incubated with different concentrations of Cu(2+). Our results showed that Cu(2+) induced a concentration and time-dependent rise in mitochondrial ROS formation, lipid peroxidation, and mitochondrial membrane potential collapse before mitochondrial swelling ensued. Increased disturbance in oxidative phosphorylation was also shown by decreased ATP concentration and decreased ATP/ADP ratio in Cu(2+)-treated isolated mitochondria. In addition, collapse of mitochondrial membrane potential (MMP), mitochondrial swelling, and release of cytochrome c following of Cu(2+) treatment were well inhibited by pretreatment of mitochondria with CsA and BHT. Our results showed that Cu(2+) could interact with respiratory complexes (I, II, and IV). This suggests that Cu(2+)-induced liver toxicity is the result of metal's disruptive effect on liver hepatocyte mitochondrial respiratory chain that is the obvious cause of Cu(2+)-induced ROS formation, lipid peroxidation, mitochondrial membrane potential decline, and cytochrome c expulsion which start cell death signaling.

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Our study showed the critical role of oxidative damage and inflammation in GM-induced nephrotoxicity that markedly inhibited by administration of watercress. Therefore, watercress can be suggested for prevention of GM-induced nephrotoxicity.

It has been shown that salicylic acid (SA) acts as an endogenous signal molecule responsible for inducing stress tolerance. The aim of the present work is to investigate the effect of sodium chloride (0, 100, and 200 mM) and exogenous SA (1 mM) on some biochemical and molecular responses of safflower. Results revealed that K + , Ca 2+ , indol-3-acetic acid (IAA), and gibberellic acid (GA) contents decreased under salinity however, Na + content, and SOS1 and NHX1 genes expression increased. Further, palmitic and oleic acids contents decreased, while stearic, linoleic, and linolenic acids content increased under salinity. Exogenous SA had a positive effect on K + , Ca 2 + , IAA, and GA contents, but decreased Na + content. In addition, SA induced expression of SOS1 and NHX1 genes in all plants. Our data indicate that SA helps safflower to better cope with salinity. The results provide new insights to mechanisms that help regulate salinity resistance in safflower. SA may be considered as a foliar application to ameliorate salinity effects, due to its low price and availability.

Previous reports suggested that certain carbohydrate polymers, such as β-(1→3)-D-glucan, may possess free radical scavenging activity. The present study examined the free radical scavenging activity of a carbohydrate polymer, β-(1→3)-D-glucan against oxidative stress induced by depleted uranium in isolated rat hepatocytes. Addition of U (VI) (uranyl acetate) to isolated rat hepatocytes results in reactive oxygen species (ROS) formation, rapid glutathione depletion, mitochondrial membrane potential collapse and lysosomal membrane rupture before hepatocyte lysis occurred. Our results showed that quite similar to silymarin, which is a known antioxidant and radical scavenger, tiny concentration of β-glucan (138 nM) very successfully protected the hepatocytes against cell lysis and all oxidative stress cytotoxicity endpoints caused by depleted uranium including ROS formation, glutathione depletion, decreased mitochondrial membrane potential, lysosomal membrane rupture and caspase 3 activity increase. In conclusion, our results confirmed the antioxidant and radical scavenging activity of β-(1→3)-D-glucan and suggested this compound and silymarin as possible drug candidates for prophylaxis and treatment against depleted uranium toxic effects.