Potential of curcumin and resveratrol as biochemical and biophysical modulators during lung cancer in rats.

The present study explored chemopreventive aspects of curcumin and resveratrol in the experimental model of lung carcinogenesis in rats. The main aim was to establish efficacy of combined phytochemicals treatment over individual treatments in rat cancer model. The study was performed in terms of both biophysical and biochemical parameters. The rats were segregated into five groups, which included normal control, benzo[a]pyrene (BP) treated, BP + curcumin treated, BP + resveratrol treated, and BP + curcumin + resveratrol treated groups. The results confirmed significant changes in the biochemical indices of the BP treated rats. Further, radiorespirometric studies showed significant rise in the 14C-glucose turnover and uptakes in BP treated rats. Also, a significant increase in the cell proliferation was noticed indirectly by recording uptakes of 3H-thymidine in the lung slices of BP treated rats. On the other hand, supplementation with curcumin and resveratrol in combination to BP treated rats significantly modulated both biophysical and biochemical indices. The histopathological studies also supported the efficacy of combined treatment of phytochemicals during lung carcinogenesis. The present study concluded that the combination of curcumin and resveratrol efficiently modulated lung carcinogenesis in rats.

Prevention of Doxorubicin-Induced Renal Toxicity by Theanine in Rats.

Doxorubicin (DOX) is a highly potent anti-neoplastic agent widely used in clinical practice, but its dosage and duration of administration are strictly limited due to dose-related organ damage. In the present study, we examined whether theanine, an amino acid derivative found in green tea leaves, can protect against DOX-induced acute nephrotoxicity in rats. Decreases in the creatinine clearance by DOX administration were attenuated by concurrent treatment with theanine, which was consistent with the change in histological renal images assessed by microscopic examination. Theanine had no effect on the distribution of DOX to the kidney. The production of lipid peroxide in the kidney after DOX administration was suppressed by concurrent treatment with theanine. Reduced glutathione content, but not superoxide dismutase activity, was decreased following DOX administration, whereas this change was suppressed when theanine was given in combination with DOX. These results suggest that theanine prevents DOX-induced acute nephrotoxicity through its antioxidant properties.

Biochemical Modulation by Carbon and Nitrogen Addition in Cultures of Dictyota menstrualis (Dictyotales, Phaeophyceae) to Generate Oil-based Bioproducts.

Dictyota menstrualis (Hoyt) Schnetter, Hörning & Weber-Peukert (Dictyotales, Phaeophyceae) was studied for the production of oil-based bioproducts and co-products. Experiments were performed to evaluate the effect of carbon dioxide (CO2) concentration, under nitrogen (NO3 (-)) limiting and saturation conditions, on growth rate (GR), photosynthesis, as well as nitrate reductase (NR), carbonic anhydrase (CA), and Rubisco activities. In addition, the biochemical composition of D. menstrualis under these conditions was estimated. GR, protein content, and N content in D. menstrualis were higher in treatments containing NO3 (-), irrespective of CO2 addition. However, when CO2 was added to medium saturated with NO3 (-), values of maximum photosynthesis, Rubisco, and NR activity, as well as total soluble carbohydrates and lipids, were increased. CA activity did not vary under the different treatments. The fatty acid profile of D. menstrualis was characterized by a high content of polyunsaturated fatty acids, especially the omega-3 fatty acids, making it a possible candidate for nutraceutical use. In addition, this species presented high GR, photosynthetic rate, and fatty acid content, highlighting its economic importance and the possibility of different biotechnological applications.

Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response.

Doxorubicin (DOX) is widely used as an antitumor agent with topoisomerase II inhibiting activity; however, its dosage and duration of administration have been strictly limited due to dose-related organ damage. The present study investigated whether theanine, an amino acid found in green tea leaves, could reduce DOX-induced acute hepatotoxicity and the apoptotic response in mice. Activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, biomarkers of hepatic impairment, were markedly increased after the administration of 20 mg/kg DOX, whereas the degree of these elevations was significantly attenuated by 10 mg/kg theanine, which was consistent with histological hepatic images assessed by microscopic examination. The hepatic expression of Bax and Fas, representative intrinsic and extrinsic apoptotic molecules, respectively, was significantly increased by dosing with DOX. However, the elevation in the hepatic expression of Bax, but not Fas, was suppressed to control levels by theanine. The formation of cleaved caspase-3 protein in the group given DOX with theanine was significantly lower than that in the group treated with DOX alone. These results suggest that theanine can protect against acute hepatic damage induced by DOX, which is attributed to the suppression of intrinsic caspase-3-dependent apoptotic signaling.

Targeting potassium channels for increasing delivery of imaging agents and therapeutics to brain tumors.

Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/capillaries that form the blood-brain barrier not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells (ECs). In this study, we validated the non-invasive and clinically relevant dynamic contrast enhancing-magnetic resonance imaging (DCE-MRI) method with invasive, clinically irrelevant but highly accurate quantitative autoradiography method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa) channel activator NS-1619. Our results show that human gliomas and brain tumor ECs that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents' delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.