Protective effect of Rumex patientia (English Spinach) roots on ferric nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion response.

In this communication, we document the antioxidant potential of ethanolic extract of Rumex patientia L. (Polygonaceae) roots and its chemopreventive effects against Fe-NTA mediated hepatic oxidative stress, hepatotoxicity and tumor promotion response. The extract exhibited high polyphenolic content, potent reducing power and significantly scavenged free radicals (including several reactive oxygen species (ROS) and reactive nitrogen species (RNS)). The extract also significantly and dose dependently protected against oxidative damage to lipids and DNA. These results indicated R. patientia root extract to exert a potent antioxidant activity in vitro. The efficacy of extract was also evaluated in vivo and it was found to exert a potent protective affect in acute oxidative tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Administration of Fe-NTA (9 mg/kg body weight, i.p.) to mice led to a significant oxidative stress and allied damage in liver tissues and induced hyperproliferation. A significant depletion was observed in GSH content and enzymes implicated in its metabolism. Attenuation also occurred in activities of other hepatic antioxidant enzymes including SOD, CAT, and GPX. Fe-NTA also incited hyperproliferation response elevating ornithine decarboxylase activity and [(3)H]-thymidine incorporation into DNA. Histopathological investigations and liver function tests (LFT) indicated Fe-NTA to cause extensive hepatic damage. However, prophylactic treatment with R. patientia root extract at a dose regimen of 100-200mg/kg body weight for a week not only restored hepatic antioxidant armory close to normal, but also significantly precluded oxidative damage restoring normal hepatic architecture and levels of hepatic damage markers. The data obtained in the present study illustrates R. patientia roots to possess potent antioxidant and free radical scavenging activities and thwart oxidative damage and hyperproliferation in hepatic tissues.     

Lycopene inhibits DNA damage and reduces hMTH1 mRNA expression in the liver of Mongolian gerbils treated with ferric nitrilotriacetate

Epidemiologic studies suggest that lycopene may reduce the risk of certain cancers, but the underlying mechanisms are unclear. We hereby examined in vivo anticarcinogenic effects of supplemental lycopene on hepatic DNA damage (Comet formation and levels of 8-oxo-2′-deoxyguanosine, 8-oxo-dG) and human MutT homologue (hMTH1) mRNA expression in Mongolian gerbils injected i.p. with ferric nitrilotriacetate (Fe/NTA). Gerbils were pre-treated with two dose (10 and 20 mg/kg BW) of lycopene on alternate morning for 10 d. Six hours after the last lycopene supplementation, the gerbils received Fe/NTA (0.16 mmol/10 mL/kg BW) and were killed 3 h later. We found that the livers of Fe/NTA-treated animals exhibited a 5-fold increase in Comet formation (expressed as tail moment), a 2.6-fold increase in 8-oxo-dG levels and a significant increase in hMTH1 mRNA expression. Supplemental lycopene completely inhibited Comet formation (P < 0.001) and significantly suppressed 8-oxo-dG levels and hMTH1 expression in a dose-dependent manner. The expression levels of hMTH1 mRNA are highly correlated with hepatic levels of 8-oxo-dG and tail moment, suggesting that hMTH1 gene expression represents a molecular marker of oxidative DNA damage. These results demonstrate the potential of lycopene as a promising chemopreventive agent against hepatotumorigenesis.     

Antioxidant and antiacetylcholinesterase activities of chard (Beta vulgaris L. var. cicla)

Plants have been used for many years as a source of traditional medicine to treat various diseases and conditions. Many of these medicinal plants are also excellent sources for phytochemicals, many of which contain potent antioxidant and antiacetylcholinesterase activities. Chard (Beta vulgaris L. var. cicla) is widely spread in Turkey and used as an antidiabetic in traditional medicine. In the present study, the antioxidant activity and acetylcholinesterase inhibitor capacity of chard were examined. In addition, proline level of chard was determined. The antioxidant activity of water extract of chard was evaluated using different antioxidant tests. The results were compared with natural and synthetic antioxidants. The results suggest that chard may provide a natural source of antioxidant and antiacetylcholinesterase activities and proline content.     

Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems

Pyrroloquinoline quinone (PQQ) is a novel redox cofactor recently found in human milk. It has been reported to function as an essential nutrient, antioxidant and redox modulator in cell culture experiments and in animal models of human diseases. As mitochondria are particularly susceptible to oxidative damage we studied the antioxidant properties of PQQ in isolated rat liver mitochondria. PQQ was an effective antioxidant protecting mitochondria against oxidative stress-induced lipid peroxidation, protein carbonyl formation and inactivation of the mitochondrial respiratory chain. In contrast, PQQ caused extensive cell death to cells in culture. This surprising effect was inhibited by catalase, and was shown to be due to the generation of hydrogen peroxide during the autoxidation of PQQ in culture medium. We conclude that the reactivities of PQQ are dependent on its environment and that it can act as an antioxidant or a pro-oxidant in different biological systems.     

The effects of vitamin A supplementation to rats during gestation and lactation upon redox parameters: Increased oxidative stress and redox modulation in mothers and their offspring

Vitamin A is an essential nutrient required in adequate amounts for reproduction and development. Subtle variations in the status of maternal nutrition may affect physiological and metabolic parameters in the fetus. Evidence suggests a key role for oxidative stress in these events. Literature is controversial about the effects of vitamin A supplementation. Here, we studied the effects of vitamin A supplementation on female Wistar rats during gestation and lactation on oxidative stress parameters of maternal and offspring tissues. Rats received daily doses of vitamin A at 2500, 12,500 and 25,000 IU/kg. We observed an increase of oxidative damage markers in the reproductive tissues and plasma of dams. The activity of glutathione-S-transferase was modulated by vitamin A supplementation. It was found to be increased in the liver of dams and decreased in the kidneys of mothers and offspring. In pups, supplementation decreased the total antioxidant potential of the liver along with decreased superoxide dismutase/catalase activity ratio in the kidney. The levels of lipoperoxidation were increased in male offspring, but decreased in female pups. Collectively, the results suggest that excessive vitamin A intake during gestation and lactation might be toxic for mothers with adverse effects for the developing offspring.     

p-Methoxyl-diphenyl diselenide protects against cisplatin-induced renal toxicity in mice

The present study was designed to investigate the effects of p-methoxyl-diphenyl diselenide (OMePhSe)₂ on oxidative stress and renal damage parameters of mice exposed to cisplatin. (OMePhSe)₂ (50 and 100 mg/kg/day) was orally administered to mice for six consecutive days. On the third day after the beginning of (OMePhSe)₂ treatment, the renal toxicity was induced by injecting cisplatin (10 mg/kg intraperitoneal) in mice. (OMePhSe)₂ treatment (50 mg/kg) partially reduced plasma urea and creatinine levels increased by cisplatin. Histopathological examination of kidneys showed that (OMePhSe)₂ ameliorated renal injury caused by cisplatin. (OMePhSe)₂ attenuated the decrease in reduced glutathione (GSH) and ascorbic acid (AA) levels, the inhibition of glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and catalase (CAT) activities caused by cisplatin in kidney. (OMePhSe)₂ treatment partially protected against the inhibition of renal δ-aminolevulinic dehydratase (δ-ALA-D) activity caused by cisplatin. No alteration in renal lipid peroxidation levels was found in cisplatin and/or (OMePhSe)₂ groups. (OMePhSe)₂ was effective against the increase in reactive species (RS) levels caused by the cisplatin exposure. Based on the renoprotective and antioxidant actions of (OMePhSe)₂ we suggest that this organoselenium compound could be considered a feasible candidate to protect against toxicity commonly encountered in cisplatin exposure.     

Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium

Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells are one of the main targets of phthalates’ testicular toxicity. Selenium is known to be involved in the modulation of intracellular redox equilibrium, and plays a critical role in testis, sperm, and reproduction. This study was aimed to investigate the oxidative stress potential of DEHP and its consequences in testicular cells, and examine the possible protective effects of selenium using the MA-10 mouse Leydig tumor cell line as a model. In the presence and absence of selenium compounds [30 nM sodium selenite (SS), and 10 μM selenomethionine (SM)], the effects of exposure to DEHP and its main metabolite mono(2-ethylhexyl)-phthalate (MEHP) on the cell viability, enzymatic and non-enzymatic antioxidant status, ROS production, p53 expression, and DNA damage by alkaline Comet assay were investigated. The overall results of this study demonstrated the cytotoxicity and genotoxicity potential of DEHP, where MEHP was found to be more potent than the parent compound. SS and SM produced almost the same level of protection against antioxidant status modifying effects, ROS and p53 inducing potentials, and DNA damaging effects of the two phthalate derivatives. It was thus shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenium status.