Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents.

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.

Ellagic acid modulates cisplatin toxicity in DMH induced colorectal cancer: Studies on membrane alterations.

Systemic toxicity due to chemotherapy contributes to poor prognosis in patients receiving chemotherapy. The present study, therefore, explores the role of Ellagic acid, a phytochemical, in modulating cisplatin (CP) toxicity in dimethylhydrazine-induced colorectal cancer. Colons excised from DMH administered animals showed abnormal crypts and bulges over the mucosal surface. SEM revealed significant alterations and dysplastic lesions in DMH administered mice. Animals receiving combined treatment showed improvement in colonic epithelium with lesser irregularities. DMH and CP administration disturbed the membrane dynamics and integrity as observed with the fluorescent probes DPH and pyrene. However, EA co-supplementation with CP proved to be beneficial in normalizing the altered membrane. Ellagic acid co-supplementation along with CP; therefore, showed great promise and helped restore the membrane alterations in the colon caused due to CP-induced toxicity and DMH insult. These observations could pave way towards developing a combination therapy targeting colon carcinogenesis in future.

Ginkgo biloba attenuates aluminum lactate-induced neurotoxicity in reproductive senescent female rats: behavioral, biochemical, and histopathological study.

Extensive use of aluminum (Al) in industry, cooking utensils, and wrapping or freezing the food items, due to its cheapness and abundance in the environment, has become a major concern. Growing evidence supports that environmental pollutant Al promotes the aggregation of amyloid beta (Aß) in the brain, which is the main pathological marker of Alzheimer's disease (AD). Further, AD- and Al-induced neurotoxic effects are more common among women following reproductive senescence due to decline in estrogen. Though clinically Ginkgo biloba extract (GBE) has been exploited as a memory enhancer, its role in Al-induced neurotoxicity in reproductive senescent female rats needs to be evaluated. Animals were exposed to intraperitoneal dose (10 mg/kg b.wt) of Al and oral dose (100 mg/kg b.wt.) of GBE daily for 6 weeks. A significant decline in the Al-induced Aß aggregates was observed in hippocampal and cortical regions of the brain with GBE supplementation, as confirmed by thioflavin (ThT) and Congo red staining. GBE administration significantly decreased the reactive oxygen species, lipid peroxidation, nitric oxide, and citrulline levels in comparison to Al-treated rats. On the contrary, a significant increase in the reduced glutathione, GSH/GSSG ratio as well as in the activities of antioxidant enzymes was observed with GBE administration. Based on the above results, GBE prevented the neuronal loss in the hippocampus and cortex, hence caused significant improvement in the learning and memory of the animals in terms of AChE activity, serotonin levels, Morris water maze, and active and passive avoidance tests. In conclusion, GBE has alleviated the behavioral, biochemical, and histopathological alterations due to Al toxicity in rats. However, molecular studies are going on to better understand the mechanism of GBE protection against the environmental toxicant Al exposure. Graphical abstract .

Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis.

The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT-IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP-induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.

Ellagic acid ameliorates cisplatin toxicity in chemically induced colon carcinogenesis.

Cis-diamminedichloroplatinum(II) (cisplatin) (CP) is an important chemotherapeutic agent used in the treatment of several cancers. However, it has several side effects including nephrotoxicity gonadotoxicity, hepatotoxicity, and ototoxicity. In in vitro experiments, antioxidants or reactive oxygen species scavengers have a cytoprotective effect on cells exposed to cisplatin (CP). Ellagic acid (EA) is one such bioactive polyphenol that is abundant in some fruits, nuts, and seeds. Various authors have reported that EA has strong antioxidant and antitumor potential. The present study was, therefore, carried out to explore the protective potential of EA on CP-induced gonadotoxicity and nephrotoxicity in colon tumor-bearing mice. Animals were divided into five groups: Group I: normal control, Group II: DMH treated. After 20 weeks of DMH treatment, the animals were divided into four subgroups, viz., Group III: no treatment, Group IV: EA, Group V: CP, and Group VI: CP + EA. Administration of EA significantly ameliorated the toxicity caused by CP as indicated by improved kidney function tests and reproductive function tests. EA treatment to CP-abused mice also led to a marked reduction in the extent of peroxidative damage to tissue as was evident from the improvement in the histopathological changes in kidney and testis. Blood counts were also improved on administration of EA to CP-treated mice. This article provides the evidence that antioxidant efficacy of EA has beneficial effects on CP-induced nephrotoxicity and gonadotoxicity and contributes to understanding the role of oxidative stress, and suggests several points as part of the mechanism of CP toxicity.

Potential chemoprotective role of resveratrol against cisplatin induced testicular damage in mice.

Semen banking is often advised to male patients undergoing chemotherapy as the damage induced is profound and often irreversible. However, low success rates of assisted reproductive techniques (ART) using banked semen have led to the quest for alternative methods to treat chemotherapy-induced infertility. The present study therefore aimed to study the role of resveratrol against cisplatin induced testicular damage. Male albino mice were divided into five groups (n = 6 each), viz. normal control, resveratrol vehicle (4% ethanol), Cisplatin (7.5 mg/kg b.wt/week for 4 weeks), Resveratrol (1 mg/kg b.wt./orally for 28 days) and Resveratrol and Cisplatin combination group. Cisplatin treatment led to an increase in the activity of lactate dehydrogenase and an increase in the levels of lipid peroxidation. Glutathione levels were found to decrease with a concomitant increase in the levels of oxidized glutathione and altered status of antioxidant enzymes. Increased DNA fragmentation was also evident which was further confirmed by histopathological and FT-IR analysis. Resveratrol treatment in combination with cisplatin showed great promise in bringing down the damage statistics to near normal values in most of the parameters studied. Further studies in this direction are however needed to develop an alternative to current procedures adopted to treat chemotherapy-induced male infertility.

A new perspective on the quercetin paradox in male reproductive dysfunction.

Dietary bioflavonoids represent a large class of polyphenolic compounds found in most plants. A significant number of flavonoids are reported to have beneficial health effects. Quercetin is one such flavonoid which has been reported to possess strong antioxidant properties. However, as far as male reproduction and fertility are concerned, controversial reports exist in the literature highlighting the antioxidant as well as a prooxidant character of quercetin, leaving much to the researcher's speculation. The present review therefore, aimed at addressing this paradoxical behavior of quercetin by taking into account the in vitro and in vivo studies conducted till date regarding its role in the maintenance of male reproductive potential. From the detailed survey of the published data, it appears that the conflicting biological effects of quercetin might relate to its dose and the redox state of the cell. Thus, the cellular toxicity of quercetin metabolites might overshadow the beneficial effects of its supplementation in subjects having reproductive dysfunction coupled with elevated oxidative stress leading to the paradoxical behavior of the flavonoid.

Curcumin sensitizes lung adenocarcinoma cells to apoptosis via intracellular redox status mediated pathway.

The present study demonstrates that curcumin acts as pro-oxidant and sensitizes human lung adenocarcinoma epithelial cells (A549) to apoptosis via intracellular redox status mediated pathway. Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. These events seem to be mediated through generation of reactive oxygen species (ROS) and superoxide radicals (SOR) and enhanced levels of lipid peroxidation. These changes were accompanied by increase in oxidized glutathione (GSSG), reduced glutathione (GSH) and gamma-glutamylcysteine synthetase (gamma-GCS) activity, but decrease in GSH/GSSG ratio. The induction of apoptosis and decrease in GSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. However, L-buthionine sulfoximine (BSO), a GSH synthesis blocking agent, further enhanced curcumin-induced ROS production and apoptosis in A549 cells. Decreased GSH/GSSG ratio seems to be a crucial factor for the activation of MAPK signaling cascade by curcumin. The study therefore, provides an insight into the molecular mechanism involved in sensitization of lung adenocarcinoma cells to apoptosis by curcumin.

Decreased glutathione levels potentiate the apoptotic efficacy of selenium: possible involvement of p38 and JNK MAPKs--in vitro studies.

The present study was designed to evaluate the apoptotic efficacy of selenium (Se) under glutathione-deprived conditions. Testicular cells were used as a model to assess the above. For the study, cells were maintained for 4 h under various treatments; control (media only), selenium (0.5 microM and 1.5 microM), BSO (20 nM), selenium + BSO (0.5 microM Se + 20 nM BSO and 1.5 microM Se + 20 nM BSO). The treated cells were harvested for various estimations viz. viability, GSH, GSSG, redox ratio, ROS generation and integrity of DNA. mRNA was extracted for RT-PCR analysis of JNK, p38, caspase 3 and Bcl-2. It was observed that the cell viability decreased concomitant with the decrease in GSH levels, increase in GSSG levels and increase in the generation of ROS in the combined treatment group in comparison to control and individual treatments. Also, there was an increase in the mRNA expression of JNK and p38 MAPK along with an increase in caspase 3 expression and decrease in Bcl-2 expression. The integrity of DNA was also found to be altered in the combined treatment. Thus, the results presented in this work agree with those earlier reports in a notion that sodium selenite causes apoptosis and the toxicity of selenite is mediated by increase of intracellular ROS. Also, reduction in endogenous GSH along with selenite treatment is associated with increased apoptosis, increased expression of p38 and JNK MAPK, decreased Bcl-2 expression, and increase in caspase-3 expression. Our data indicates that GSH participates in apoptosis in testicular cells and that depletion of this molecule may be critical in predisposing these cells to apoptotic cell death.