Hepatoprotective effects of Nigella sativa seed extract against acetaminophen-induced oxidative stress

OBJECTIVE@#To investigate the protective effects of Nigella sativa seed extract (NSSE) against acetaminophen (APAP)-induced hepatotoxicity in TIB-73 cells and rats.@*METHODS@#Toxicity in TIB-73 cells was induced with 10 μmol/L APAP and the protective effects of NSSE were evaluated at 25, 50, 75, 100 μg/mL. For in vivo examination, a total of 30 rats were equally divided into five experimental groups; normal control (vehicle), APAP (800 mg/kg body weight single IP injection) as a hepatotoxic control, and three APAP and NS pretreated (2 weeks) groups (APAP + NSSE 100 mg; APAP + NSSE 300 mg and APAP + NSSE 900 mg/kg).@*RESULTS@#TIB-73 cell viability was drastically decreased by (49.0 ± 1.9)% after the 10 μmol/LAPAP treatment, which also increased reactive oxygen species production. Co-treatment with NSSE at 25, 50, 75, and 100 μg/mL significantly improved cell viability and suppressed reactive oxygen species generation. In vivo, the APAP induced alterations in blood lactate levels, pH, anionic gap, and ion levels (HCO3(-), Mg(2+) and K(+)), which tended to normalize with the NSSE pretreatment. The NSSE also significantly decreased elevated serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase induced by APAP, which correlated with decreased levels of hepatic lipid peroxidation (malondialdehyde), increased superoxide dismutase levels, and reduced glutathione concentrations. Improved hepatic histology was also found in the treatment groups other than APAP group.@*CONCLUSIONS@#The in vitro and in vivo findings of this study demonstrated that the NSSE has protective effects against APAP-induced hepatotoxicity and metabolic disturbances by improving antioxidant activities and suppressing both lipid peroxidation and ROS generation.

Hepatoprotective effects of Nigella sativa seed extract against acetaminophen-induced oxidative stress

Objective: To investigate the protective effects of Nigella sativa seed extract (NSSE) against acetaminophen (APAP)-induced hepatotoxicity in TIB-73 cells and rats. Methods: Toxicity in TIB-73 cells was induced with 10 μmol/L APAP and the protective effects of NSSE were evaluated at 25, 50, 75, 100 μg/mL. For in vivo examination, a total of 30 rats were equally divided into five experimental groups; normal control (vehicle), APAP (800 mg/kg body weight single IP injection) as a hepatotoxic control, and three APAP and NS pretreated (2 weeks) groups (APAP + NSSE 100 mg; APAP + NSSE 300 mg and APAP + NSSE 900 mg/kg). Results: TIB-73 cell viability was drastically decreased by (49.0 ± 1.9)% after the 10 μmol/LAPAP treatment, which also increased reactive oxygen species production. Co-treatment with NSSE at 25, 50, 75, and 100 μg/mL significantly improved cell viability and suppressed reactive oxygen species generation. In vivo, the APAP induced alterations in blood lactate levels, pH, anionic gap, and ion levels (HCO

Korean red ginseng prevents ethanol-induced hepatotoxicity in isolated perfused rat liver / 대한수의학회지

Alcohol abuse and its medical and social consequences are a major health problem in many areas of the world. Korean red ginseng (KRG) has been traditionally used for the treatment of liver disease. This study was conducted to evaluate the hepatoprotective effects of KRG against hepatotoxicity in Sprague-Dawley rats treated with ethanol (EtOH). Administration of EtOH for 20 days induced significant changes in serum biochemical parameters (aspartate aminotransferase, alanine transaminase, and glucose) accompanied by histological changes in the liver tissue. Treatment with KRG prior to administration of EtOH inhibited the EtOH-induced biochemical and histological changes of the liver. In perfused rat livers, administration of EtOH caused an increase in lactate dehydrogenase (LDH) release into the perfusate and activated the pro-apoptotic Bax protein but inhibited the anti-apoptotic Bcl-2 protein. Pretreatment with KRG prior to administration of EtOH decreased the EtOH-induced LDH release and inhibition of Bcl-2 protein. These results suggest that KRG exerts anti-apoptotic effects and alleviated EtOH-induced liver injury in rats.

pH-dependent modulation of intracellular free magnesium ions with ionselective electrodes in papillary muscle of guinea pig

A change in pH can alter the intracellular concentration of electrolytes such as intracellular Ca2+ and Na+ ([Na+]i) that are important for the cardiac function. For the determination of the role of pH in the cardiac magnesium homeostasis, the intracellular Mg2+ concentration ([Mg2+]i), membrane potential and contraction in the papillary muscle of guinea pigs using ion-selective electrodes changing extracellular pH ([pH]o) or intracellular pH ([pH]i) were measured in this study. A high CO2-induced low [pH]o causes a significant increase in the [Mg2+]i and [Na+]i, which was accompanied by a decrease in the membrane potential and twitch force. The high [pH]o had the opposite effect. These effects were reversible in both the beating and quiescent muscles. The low [pH]o-induced increase in [Mg2+]i occurred in the absence of [Mg2+]o. The [Mg2+]i was increased by the low [pH]i induced by propionate. The [Mg2+]i was increased by the low [pH]i induced by NH4Cl-prepulse and decreased by the recovery of [pH]i induced by the removal of NH4Cl. These results suggest that the pH can modulate [Mg2+]i with a reverse relationship in heart, probably by affecting the intracellular Mg2+ homeostasis, but not by Mg2+ transport across the sarcolemma.

Regulation of magnesium release by cAMP during chemical hypoxia in the rat heart and isolated ventricular myocytes

Chemically induced hypoxia has been shown to induce a depletion of ATP. Since intracellular free Mg2+ ((Mg2+)i) appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in (Mg2+)i would result in Mg2+ extrusion following hormonal stimulation. To determine the relation between Mg2+ efflux and cellular energy state in a hypoxic rat heart and isolated myocytes, (Mg2+)i, ATP and Mg2+ content were measured by using mag-fura-2, luciferin-luciferase and atomic absorbance spectrophotometry. Mg2+ effluxes were stimulated by norepinephrine (NE) or cAMP analogues, respectively. Mg2+ effluxes induced by NE or cAMP were more stimulated in the presence of metabolic inhibitors (MI). Chemical hypoxia with NaCN (2 mM) caused a rapid decrease of cellular ATP within 1 min. Measurement of (Mg2+)i confirmed that ATP depletion was accompanied by an increase in (Mg2+)i. No change in Mg2+ efflux was observed when cells were incubated with MI. In the presence of MI, the cAMP-induced Mg2+ effluxes were inhibited by quinidine, imipramine, and removal of extracellular Na+. In addition, after several min of perfusion with Na+-free buffer, a large increase in Mg2+ efflux occurred when Na+-free buffer was switched to 120 mM Na+ containing buffer. A similar Mg2+ efflux was observed in myocytes. These effluxes were inhibited by quinidine and imipramine. These results indicate that the activation of Mg2+ effluxes by hormonal stimulation is directly dependent on intracellular Mg2+ contents and that these Mg2+ effluxes appear to occur through the Na+-dependent Na+/Mg2+ exchange system during chemical hypoxia.