Rutin, an antioxidant flavonoid, induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium-induced oxidative stress in the testis of adult rats

This study was designed to determine the ulcer-protecting effects of rutin, a natural flavone, against gastric lesions induced by 50% ethanol, the experimental model related to lesion pathogenesis with production of reactive species. The possible involvement of sulphydryl compounds (SH), neutrophil infiltration, and the capacity of this flavone to restrain the oxidative process produced in the gastric tissue were also investigated. The levels of thiobarbituric acid (TBA, as index of lipid peroxidation), the myeloperoxidase activity (MPO, as a marker of neutrophil infiltration), the content of mucosal sulphydryls (SH) groups and the activity of glutathione peroxidase (GSH-Px, an important antioxidant enzyme) were determined. Pretreatment with the highest dose of rutin (200 mg/kg), 120 min before 50% ethanol, resulted in the most effective necrosis prevention. TBA reactive substances in the gastric mucosa, were increased by ethanol injury, and this increase was inhibited by the administration of 200 mg/kg of rutin. However, the flavonoid was not able to modify the ethanol-induced neutrophil infiltrate expressed as myeloperoxidase activity. Exposure of the gastric mucosa to 50% ethanol induced a significant diminution in gastric non-protein SH content; this parameter also was not modified by the treatment with rutin. GSH-Px activity decreased in the gastric mucosa after ethanol-treatment. In contrast, rutin at all tested doses induced a significant increase in this enzymatic activity, higher than in control group. These results suggest that the gastroprotective effect of rutin in this experimental model appears through an anti-lipoperoxidant effect, and also by enhancement of the anti-oxidant enzymatic (GSH-Px) activity.

Cyclophosphamide is a potent anticancer agent. However its clinical use is restricted because of its marked organ toxicity associated with increased oxidative stress and inflammation. The present study was designed to demonstrate the protective effects of rutin, a naturally occurring bioflavonoid against the hepatotoxicity induced by CP. Rats were subjected to oral pretreatment of rutin (50 and 100 mg/kg b wt) against hepatotoxicity induced by i.p. injection of CP (150 mg/kg b wt) and were sacrificed after 24 h. Hepatoprotective effects of rutin were associated with upregulation of antioxidant enzyme activities and down regulation of serum toxicity markers. Rutin was able to down regulate the levels of inflammatory markers like TNF-α, IL-6 and expressions of p38-MAPK, NFκB, i-NOS and COX-2. Histopathological changes further confirmed the biochemical and immunohistochemical results showing that CP caused significant structural damage to liver which were reversed by pretreatment of rutin. Therefore, our study revealed that rutin may be a promising modulator in attenuating CP induced oxidative stress, inflammation and hepatotoxicity via targeting NFκB and MAPK pathway.

Dietary quercetin (QU) and rutin (RU), phenolic flavonoids commonly found in many fruits and vegetables, were provided to CF1 female mice for 50 weeks to assess the ability of these compounds to inhibit azoxymethanol (AOM)-induced colonic neoplasia. In addition to a control group fed an AIN 76A diet, five other groups received that diet to which was added either 0.1, 0.5 or 2.0% QU and 1.0 or 4.0% RU. Acute studies revealed that, among saline controls, no alteration of any proliferative parameters of colonic epithelial cells was observed among those groups receiving any dose of QU or RU. However, among the AOM-treated mice, both 2% QU and 4% RU significantly reduced hyperproliferation and inhibited the shift of S-phase cells to the middle and upper portion of crypts. Moreover, mice fed these concentrations of QU and RU had significantly fewer AOM-induced focal areas of dysplasia (FADs) than those fed the control diet (0.2 +/- 0.4 and 0.4 +/- 0.5 versus 3.6 +/- 2.3 respectively). Tumors occurred more frequently in the distal half of the colon, regardless of treatment. Compared with controls, mice fed 2% QU had a significantly reduced tumor incidence (25.0% versus 5.9%, P = 0.03). Those fed 4% RU showed only a trend toward inhibition (25% versus 9.7%, P = 0.11). Nevertheless, both 2% QU and 4% RU suppressed tumor multiplicity, i.e. fewer tumors/animal arose in these groups than in the AOM-treated control mice (1.2 versus 2.3, P = 0.005; 1.1 versus 2.3, P = 0.003 respectively). Clearly, QU and RU exhibit significant activity in reducing AOM-induced hyperproliferation of colonic epithelial cells and FAD incidence. This behavior successfully forecast the ability of both flavonoids to suppress tumor multiplicity and ultimately tumor development.