Biomedicine & Preventive Nutrition最新文献

Objective

To investigate the protective effect of leaf extract of Solanum trilobatum (ELEST) against benzo(a)pyrene (BP) induced lung carcinogenesis.

Methods

Experiment was designed with the treatment regimen of ELEST [200 mg/kg body weight dissolved in dimethyl sulphoxide(DMSO)] for 4 weeks before (pre-initiation) and from 12th week after B(a)P (50 mg/kg body weight) induced lung carcinoma(post-initation).

Results

Administration of BP (50 mg/kg body weight) resulted in increased lipid peroxidation (LPO) and marker enzymes, such as arylhydrocarbon hydroxylase (AHH), gamma-glutamyl transpeptidase (γGT), 5′-nucleotidase (5′ND) and lactate dehydrogenase (LDH) along with decrease in the levels of tissue antioxidants, like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C in mice. Significantly, ELEST modulated these alterations suggest the efficacy of ELEST in the chemotherapeutics of lung cancer. The histopathological studies also evidenced the protective efficiency of the extract against lung carcinogenesis. Further, significant increase in the levels of Cytochrome P₄₅₀, Cytochrome b₅, NADPH Cyt c reductase and decrease in UDP-glucuronyl transferase and quinone reductase was observed in microsomal fraction of lung and liver of BP-induced mice, whereas the treatment with ELEST resulted in reversal of modulations observed in the activities of detoxification enzymes.

Conclusions

Collectively, the present observations indicate that the treatment with ELEST exhibited protective and antioxidant effect against BP-induced lung carcinogenesis.

Exposure to pyrethroid pesticides has been associated with adverse neurodevelopmental outcomes, like neurodegenerative disorder, low IQ, pervasive developmental disorder, attention problems. Thus, we investigated the relationship between pyrethroid deltamethrin exposure to acetylcholine esterase, ATPase, oxidative stress biomarkers, and impaired behavior performance, and the possible ameliorating mechanism of dietary flavonoid naringin in male Wistar rats. Adult male wistar rats were divided into four different groups. Group I: control group; group II received DLM dissolved in corn oil 12.8 mg/kg BW orally (1/10 LD₅₀) for three weeks; group III received DLM as group II and naringin (100 mg/kg BW for 21 days) orally. Group IV: naringin alone. DLM exposure leads to reduction in the levels of acetylcholinesterase, Na⁺/K⁺, Ca²⁺, Mg²⁺ ATPase, enzymic and non-enzymic antioxidants activities in cortex and hippocampus region and increase the activities of TBARS. DLM-induced neuronal alterations was evidenced by impairment behavioral performance, like memory, anxiety, locomotor, and emotionality behaviors. This is also supported by histopathological findings of cortex and hippocampus region of rats. However, naringin treatment modulates the abnormalities of DLM-induced alterations in oxidative stress biomarkers, acetylcholine esterase, ATPase, and behavioral performance of rats. These findings highlight the efficacy of naringin as neuroprotectant. In conclusion, our results demonstrated that DLM cause neurobehavioral and biochemical alterations. Oxidative stress, free radical mechanism play major role on DLM-induced neurotoxicity. Naringin could be a suitable agent for preventing the toxicity of DLM by its potent antioxidant, free radical scavenging and neuroprotective activity.

Epidermal growth factor (EGF) plays a key role in epithelial malignancies by enhancing cancer cell proliferation, survival, invasion, and metastasis. The aberrant expression of epidermal growth factor receptor (EGFR) by tumors typically confers a more aggressive phenotype and is often predictive of poor prognosis. Quercetin is an anti-oxidative flavonoid widely distributed in fruits and vegetables and have attracted much attention as potential anti-carcinogens. Prostate cancer is the most common cause of cancer related deaths in men. In the present study, we examined the effects of quercetin on EGF induced signaling molecules involved in proliferation, survival and apoptosis in PC-3 cells. EGF-stimulated EGFR, Akt, PI3 K, PDK1 and ERK1/2 protein levels were inhibited by quercetin. The inhibitory effects of quercetin on EGF induced signaling were compared with PI3 K inhibitor (LY294002) and MAPK inhibitor (PD98059). Quercetin down-regulated EGF induced Bcl-2 expression and upregulated Bax protein levels. Caspase-3 activity was significantly increased by quercetin treatment. Acridine orange and ethidium bromide staining showed that quercetin was able to induce apoptosis even in the presence of EGF. To conclude, the present study showed that quercetin inhibits EGF induced cell survival, proliferation and induced apoptosis in PC-3 cells.

An isoprenylated flavonoid was isolated from the aerial parts of the Spilanthes calva D.C. The structure of the isolated compound was ascertained by UV, IR, ¹H NMR, ¹³C NMR and mass analyses. The structure was elucidated as 6-(3-methylbut-1-enyl)-5,7-dimethoxy-4′-hydroxy flavone. The isolated compound was further evaluated by in vitro xanthine oxidase enzyme activity. Molecular docking study was carried out to establish the binding mode of isolated compound in the inhibitor-binding cavity of enzyme. The isoprenylated flavonoid was found to be possess potent xanthine oxidase inhibition activity with an IC₅₀ of 16.56 μM. Molecular docking study revealed that the potent action of the compound was due to the hydrogen bonding to ALA 1079 and π–π stacking interaction with PHE 914 in the inhibitor-binding cavity of xanthine oxidase.

New strategies for the prevention of colon cancer persists a crucial need. However, resistance to current chemopreventive drugs is relatively prevalent in colon carcinogenesis. For this intent, a chemopreventive study was acquitted to elucidate the probable effect of taxifolin (TAX) against 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis in mice and to evaluate its efficacy with 5-fluorouracil (5-FU) drug control. Swiss Albino mice were intended for colon carcinogenesis received subcutaneous injections of DMH (20 mg/kg bw., sc) once a week for 15 weeks and were treated with TAX (4 μg/kg bw, op) and 5-FU drug control (10 mg/kg bw., op) for the entire study period. Our results unveil that mice administered with TAX significantly modulates DMH induced histological alterations (ACF, AgNORs, and mucin depletion). Moreover, TAX treatment also inhibits DMH mediated oxidative damage by diminishing tissue lipid peroxidation (MDA, MPO and CD) accompanied by enhanced activities of enhanced activities of free radical metabolizing enzymes (SOD, CAT, GPx, GR, GSH, vitamin A, C and E). Apoptotic and proliferating cell nuclear antigen (PCNA) findings also revealed that treatment with TAX substantially regulates cell proliferation through the increased extent of DNA fragmentation. The incidence of colon cancer in TAX treated mice was significantly reduced when compared to that of 5-FU control. Our findings concluded that taxifolin act as an effective chemopreventive agent against colon carcinogenesis by its virtue of antioxidant mediated apoptosis and anti-proliferative activities.

The objective of this study was to investigate the antioxidant potential of turmeric (TMR) (1% turmeric-diet) against the renal toxicity induced by deltamethrin (DLM) (41 ppm) in rats. Male Wistar rats were randomly divided into four groups of sex each: a control group and three treated groups during 7 weeks with TMR alone and DLM administrated either alone in drinking water for DLM group or co-administred with TMR for DLM + TMR group. Results showed that DLM caused a significant reduction in body weight and kidney absolute and relative weight and decreased antioxidant enzyme activity accompanied by significant (P < 0.001) increased renal MDA, serum urea and creatinine levels compared to control. Histopathologically, DLM caused dilatation of proximal tubules, tubular cell desquamation, inflammatory cell infiltration, degeneration and necrosis. TMR co-administration significantly restored oxidative enzymes activity, serum biochemistry, MDA level and histological alterations caused by DLM. However, all these changes were monitored by Fourier transform–infrared spectroscopy (FT–IR) technique, reflecting the alteration in the biomolecules due to the oxidative stress caused by DLM intoxication. While, TMR co-administration brought them near to the control, it can be concluded that TMR has beneficial influences and could be able to antagonize DLM caused oxidative stress, changes in serum biochemistry and histopathological alterations in male Wister rats.

We examined the effects of phytoestrogen genistein on zebrafish caudal fin regeneration and found that genistein could inhibit fin generation in μM concentration. Fish were injected with varying concentrations (10–100 μM) of genistein for 5 days after caudal fin amputation, and regeneration of the fin was evaluated by analyzing caudal fin length and newly formed vascular region. Regeneration of amputated fins was inhibited or delayed to the maximum of 64.7% in dorsal region, 63.35% in cleft region and 66.54% in ventral region after genistein treatment unlike the control that completely regenerated their fins after 5 days post-amputation (DPA). PCR data showed a clear reduction in vascular endothelial growth factor (VEGF) expression on exposure to genistein while a complete inhibition was observed with sunitinib (SU 11652) an inhibitor of VEGF signaling. The ability of genistein to inhibit regenerative angiogenesis of caudal fin probably by down regulating VEGF, the key player of angiogenesis and the results obtained with SU 11652 is suggestive of the involvement of VEGF signaling during regeneration. These results demonstrate that zebrafish could be a good model in elucidating molecular mechanisms that are responsible for fin regeneration.

The anti-nociceptive effect of Rhizophora mucronata was evaluated on chemically and thermally induced nociception in mice. Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction (Alk-CF) of R. mucronata by oral administration. Compared with controls, Alk-CF decreased the writhing numbers (P < 0.01) in a dose-dependent manner. Further, we determined that Alk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as luteolin. Docking simulation demonstrated that luteolin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. This study identified peripheral and central anti-nociceptive activities of R. mucronata that involve opioid receptor, and in which the active compound is luteolin as a source of new anti-nociceptive agent.

NADPH oxidase mediated ROS generation plays a decisive role in the pathogenesis of arsenic (As) hepatotoxicity. Antioxidant phytochemicals, like dimethoxycurcumin (DiMC) has a tremendous scope in attenuating the ROS mediated hepatic injury. Hence, the present study has been designed to investigate the hepatoprotective action of DiMC by analysing the markers of hepatic oxidative stress, pro-inflammatory cytokines, apoptotic markers and antioxidant competence in As (5 mg/kg BW) induced hepatotoxic rats. Oral administration of DiMC (80 mg/kg BW) to As intoxicated rats showed a significant amelioration in the levels of serum hepatic markers, pro-inflammatory cytokines and the expression of NADPH oxidase subunits (Nox2, Nox4, and p47phox) in liver. The elevated levels of hepatic oxidative stress markers lipid peroxides, hydroperoxides, protein carbonyls and conjugated dienes and decreased levels of enzymatic and non-enzymatic antioxidants status were also reverted back to near normalcy by DiMC when compared with As treated rats. In addition, mRNA and protein expression analysis also confirms that DiMC pre-treatment significantly downregulates the NOX subunits and upregulates the Nrf2 and its related enzymes in the liver. Studies on the mechanism of apoptosis showed that As accelerated the markers of mitochondrial dependent apoptotic pathway (enhanced cytochrome c release in cytosol from mitochondria, altered the expression of Bax, Bcl-2, Bad, caspase-9, caspase-3). However, DiMC pre-treatment effectively restored the As-induced alterations in liver. Histological and immunohistochemical results were also evidenced that DiMC potentially protects the liver from As-induced oxidative stress, inflammation and apoptosis. These findings encourage the use of DiMC as a prospective salutary entity for As hepatotoxicty through the suppression of NADPH oxidase and Nrf2 activation.

The liver is a major target organ for thyroid hormone action and marked changes occur in liver functions in the case of hypo- or hyperthyroidism. This studied aimed at inverstigating the biochemical and histopathological changes in the liver after thyroidectomy and the ameliorating role of Ginkgo biloba leaf extract (GLE). A total of 50 male albino rats were equally divided into five groups; 1st to 3rd groups were control, sham operated and GLE groups while 4th group was thyroidectomized rat group and 5th group was treated thyrodectomized rat with GLE. Serum T₃ and T₄ levels after 3 weeks of thyroidectomy was significantly decreased when compared with the control group, while TSH significantly increased when compared with the control group increased. Serum ALT, AST, ALP and GGT showed significant (P < 0.05) increase in thyroidectomized group when compared with control, sham operated and sham operated with GLE groups. On the one hand, treatment of thyroidectomized rats with GLE improved this increase in serum ALT, AST, ALP and GGT in thyroidectomized rat group. Liver sections of thyroidectomy group showed marked positive reaction and increase number of PCNA staining of hepatocyte nuclei. On the other hand, liver in treated of thyroidectomized rat with GLE group showed a marked reduction in the number of PCNA-positive nuclei when compared with sections in thyroidectomy group. Treatment of thyroidectomized rat with GLE improves the biochemical, histopathological and immunohistochemical alternations and the intensity of PCNA immunoreactive cells demonstrating the recovery of some injury.