The hepatoprotective potential of saponarin, isolated from Gypsophila trichotoma, was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol-induced liver injury. In freshly isolated rat hepatocytes, paracetamol (100 μmol) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60–0.006 μg/mL) preincubation, however, significantly ameliorated paracetamol-induced hepatotoxicity in a concentration-dependent manner. The beneficial effect of saponarin was also observed in vivo. Rats were challenged with paracetamol alone (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and decrease in cell GSH levels and antioxidant defence system. No changes in phase I enzyme activities of AH and EMND and cytochrome P 450 quantity were detected. Saponarin pretreatment resulted in significant increase in cell antioxidant defence system and GSH levels and decrease in lipid peroxidation. The biochemical changes are in good correlation with the histopathological data. Protective activity of saponarin was similar to the activity of positive control silymarin. On the basis of these results, it can be concluded that saponarin exerts antioxidant and hepatoprotective activity against paracetamol liver injury in vitro/in vivo.

Five benzophenones and a xanthone, isolated from Hypericum annulatum Moris, were investigated for their protective effect against carbon tetrachloride toxicity in isolated rat hepatocytes. The benzophenones and the xanthone gentisein were administered alone (100 microM) and in combination with CCl4 (86 microM). CCl4 undergoes dehalogenation in the liver endoplasmic reticulum. This process leads to trichlormethyl radical (*CCl3) formation, initiation of lipid peroxidation, and measurable toxic effects on the hepatocytes. The levels of thiobarbituric acid reactive substances (TBARS) were assayed as an index of lipid peroxidation (LPO). Lactate dehydrogenase (LDH) leakage, cell viability and reduced glutathione (GSH) depletion were used as signs of cytotoxicity. CCl4 significantly decreased hepatocyte viability, GSH level and increased TBARS level and LDH leakage as compared to the control. Our data indicate that 2,3',5',6-tetrahydroxy-4-methoxybenzophenone, 2-O-alpha-L-arabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone and 2-O-alpha-L-3'-acetylarabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone showed weaker toxic effects compared to CCl4 and in combination showed statistically significant protection against the toxic agent.

Oxidative stress is critically involved in a variety of diseases. Reactive oxygen species (ROS) are highly toxic molecules that are generated during the body's metabolic reactions and can react with and damage some cellular molecules such as lipids, proteins, or DNA. Liver is an important target of the oxidative stress because of its exposure to various prooxidant toxic compounds as well as of its metabolic function and ability to transform some xenobiotics to reactive toxic metabolites (as ROS). To investigate the processes of liver injuries and especially liver oxidative damages there are many experimental models, some of which we discuss further.

The antioxidant effect of saponarin, which is the main flavone isolated from Gypsophila trichotoma Wend., and its protection against cocaine hepatotoxicity were investigated in male Wistar rats. The animals were treated with cocaine (40 mg/kg i.p.) alone and also after 3 consecutive days of pretreatment with saponarin (80 mg/kg p.o.). After 18 hours the rats were sacrificed by decapitation. The production of thiobarbituric acid reactive substances, reduced glutathione (GSH) and the activity of the following antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were assessed in liver homogenate. Administered alone, cocaine induced significant hepatotoxicity manifested with GSH depletion and reduced antioxidant defences. Saponarin pretreatment, however, decreased cocaine toxicity both by increasing GSH levels and antioxidant enzyme activities. The results of this study proved the antioxidant activity of saponarin and its protective effect against cocaine-induced oxidative stress and hepatotoxicity.

In this study, the in vivo effects of a purified saponin mixture (PSM), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol (PC) and carbon tetrachloride (CCl4 ). The effects of PSM were compared with silymarin. Male Wistar rats were challenged orally with 20% CCl4 or PC (2 g/kg) four days after being pre-treated with PSM (100 mg/kg) or silymarin (200 mg/kg). A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl4 and PC administration alone. PSM pre-treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH. Biotransformation phase I enzymes were also assessed in both models. In the CCl4 hepatotoxicity model, pre-treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine-N-demethylase and aniline 4-hydroxylase activity and cytochrome P450, compared to the CCl4 only group. Neither silymarin nor PSM influenced PC biotransformation. Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl4 and PC-induced liver damage comparable to that of silymarin.

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A new model aqueous solution of indomethacin was developed on the basis of Pluronic F68 (15%) and F127 (10%). They showed some practical advantages over the models prepared with polyols and polysorbate 80, which were used for comparison. It was found that both Pluronics acted very similarly and were more effective as solubilizers, created an appropriate viscosity, and formed reversible gels at higher temperatures, ensured the indomethacin chemical stability and prolonged in vitro drug diffusion, and showed high physiological tolerance on rabbit eyes. Moreover, indomethacin stability and solution viscosity in the presence of Pluronics did not change after heat sterilization (i.e., the samples can bear heat sterilization).

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