Pomegranate peel extract protects against carbon tetrachloride-induced nephrotoxicity in mice through increasing antioxidants status.

Carbon tetrachloride (CCl4) is a notorious environmental pollutant known for its toxicity. The aim of the present study was to evaluate the possible protective effects of aqueous pomegranate peel extract (PPE) against CCl4 induced nephrotoxicity in mice. Adult male mice were divided into four groups: Group one was used as the control; Group two was treated with a daily oral dose of PPE (400 mg/kg) for 15 days; the third group was intraperitoneally injected with a dose (1 ml/kg) of CCl4 twice a week for two weeks; and the final group was injected with the same dose of CCl4 twice a week concomitantly with a daily oral dose of PPE (400 mg/kg). Biochemical and histopathological data were analyzed along with the gene expression levels of the antioxidant enzymes and immunohistochemistry of the kidney tissue. CCl4 resulted in a significant increase in the serum urea and creatinine levels with detectable degenerative changes in the Bowman's capsule and glomerulus, with cells exhibiting vacuolization and evidence of necrosis. Co-administration of animals with CCl4 and PPE resulted in improved biochemical and histopathological conditions. Similarly, increased production of the Caspase-3 and collagen fibers were reduced in mice treated with PPE. Quantitative analysis of superoxide dismutase, catalase and glutathione peroxidase further accentuated the effects of PPE treatment significantly improving the conditions of the CCl4-administered group. The results of the present study demonstrate that the phenolic derivative rich PPE is a potent nephroprotective agent and suppresses CCl4-induced nephrotoxicity in mice.

2-Hydroxy-4-methoxy benzoic acid attenuates the carbon tetra chloride-induced hepatotoxicity and its lipid abnormalities in rats via anti-inflammatory and antioxidant mechanism.

BACKGROUND AND AIM: Liver inflammation stimulates various inflammatory cytokines and initiates injury through oxidative stress. The aim of this study was to curtaile the liver injury through natural principles such as 2-hydroxy-4-methoxy benzoic acid (HMBA). METHODS: The current study examines the hepatoprotective and lipid lowering effect of HMBA against carbon tetra chloride (CCl4)-mediated liver toxicity in male Wistar rats. RESULTS: The hepatoprotective effects of HMBA against CCl4-induced liver damage, were evident from low serum transaminases activities, reduced hepatic lipid peroxidation and collagen content, restoration of total glutathione, and recouping of the inflammatory cytokines, such as TNF-α, IL-1ß, IL-10, and IL-6 levels. Further it was found that the treatment of HMBA, significantly lowered (P<0.01) the levels of total cholesterol, triglycerides, free fatty acids and phospholipids in serum and liver. To investigate the mechanism behind the hepatoprotective and lipid lowering effect, the activities of heme oxygenase (HO1), and myeloperoxidase (MPO) were measured and expression levels were quantified through western blot following HMBA administration. The results showed that HMBA administration significantly decreased the activity of HO1 (P<0.001), and increased the activity of MPO (P<0.001); further similar finding was observed in western analysis. The hepatoprotective, lipid lowering and shifting key defensive enzyme activities are similar to that of standard drug such as N-acetylcysteine. CONCLUSION: HMBA is competent of shielding liver from CCl4-induced hepatotoxicity, and this is associated with the lipid lowering, inflammatory cytokine restoration and induction of defensive enzyme activities.

CCl4 induces tissue-type plasminogen activator in rat brain; protective effects of oregano, rosemary or vitamin E.

The high metabolic rate and relatively low antioxidant defenses of the lipid-rich brain tissue render it highly susceptible to reactive oxygen species (ROS) and oxidative stress, whereas the implication of ROS in the pathogenesis of several diseases in the central nervous system is well-established. The plasminogen activator (PA) system is a key modulator of extracellular proteolysis, extracellular matrix remodeling and neuronal cell signaling and has been implicated in the pathogenesis of these diseases. This study evaluates the role of tissue-type PA (t-PA) in oxidative stress and the protective role of dietary antioxidants in the rat brain. We used the CCl4 experimental model of ROS-induced lipid peroxidation and evaluated the antioxidant effect of oregano, rosemary or vitamin E. CCl4-treated Wistar rats exhibited elevated brain t-PA activity, which was decreased upon long-term administration of oregano, rosemary or vitamin E. PA inhibitor-1 (PAI-1) activity was also slightly elevated by CCl4, but this increase was not affected by the antioxidants. We hypothesize that the CCl4-induced t-PA activity indicates extracellular proteolytic activity that may be linked to neuronal cell death and brain damage. Vitamin E or antioxidants present in oregano or rosemary are effective in inhibiting t-PA elevation and can be considered as a potential protection against neuronal damage.

Brazilian Bidens pilosa Linné yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects.

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC(50)~4.3-32.3 µg/ml) followed by the crude extract (IC(50)~14.2-98.0 µg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6±0.2 and 2.1±0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3'-dimethyl ether 7-O-ß-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl(4)-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl(4)-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (~60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases.