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At the molecular level, several developmental signaling pathways, such as Wnt/β-catenin, have been associated with the initiation and subsequent progression of prostate carcinomas. The present report elucidated the anti-cancerous attributes of an anthraquinone, aloe-emodin (AE), against androgen-independent human prostate cancer DU145 cells. The cytotoxicity profiling of AE showed that it exerted significant cytotoxic effects and increased lactose dehydrogenase levels in DU145 cells (p < 0.01 and p < 0.001). AE also induced considerable reactive oxygen species (ROS)-mediated oxidative stress, which escalated at higher AE concentrations of 20 and 25 µM. AE also efficiently instigated nuclear fragmentation and condensation concomitantly, followed by the activation of caspase-3 and -9 within DU145 cells. AE further reduced the viability of mitochondria with increased cytosolic cytochrome-c levels (p < 0.01 and p < 0.001) in DU145 cells. Importantly, AE exposure was also correlated with reduced Wnt2 and β-catenin mRNA levels along with their target genes, including cyclin D1 and c-myc. Furthermore, the molecular mechanism of AE was evaluated by performing molecular docking studies with Wnt2 and β-catenin. Evidently, AE exhibited good binding energy scores toward Wnt2 and β-catenin comparable with their respective standards, CCT036477 (Wnt2 inhibitor) and FH535 (β-catenin inhibitor). Thus, it may be considered that AE was competent in exerting anti-growth effects against DU145 androgen-independent prostate cancer cells plausibly by modulating the expression of Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

At the molecular level, several developmental signaling pathways, such as Wnt/β-catenin, have been associated with the initiation and subsequent progression of prostate carcinomas. The present report elucidated the anti-cancerous attributes of an anthraquinone, aloe-emodin (AE), against androgen-independent human prostate cancer DU145 cells. The cytotoxicity profiling of AE showed that it exerted significant cytotoxic effects and increased lactose dehydrogenase levels in DU145 cells (p < 0.01 and p < 0.001). AE also induced considerable reactive oxygen species (ROS)-mediated oxidative stress, which escalated at higher AE concentrations of 20 and 25 μM. AE also efficiently instigated nuclear fragmentation and condensation concomitantly, followed by the activation of caspase-3 and -9 within DU145 cells. AE further reduced the viability of mitochondria with increased cytosolic cytochrome-c levels (p < 0.01 and p < 0.001) in DU145 cells. Importantly, AE exposure was also correlated with reduced Wnt2 and β-catenin mRNA levels along with their target genes, including cyclin D1 and c-myc. Furthermore, the molecular mechanism of AE was evaluated by performing molecular docking studies with Wnt2 and β-catenin. Evidently, AE exhibited good binding energy scores toward Wnt2 and β-catenin comparable with their respective standards, CCT036477 (Wnt2 inhibitor) and FH535 (β-catenin inhibitor). Thus, it may be considered that AE was competent in exerting anti-growth effects against DU145 androgen-independent prostate cancer cells plausibly by modulating the expression of Wnt/β-catenin signaling.

Objective(s): The current study aimed to assess cisplatin-mediated ovarian apoptosis in a rat model by Royal jelly (RJ). Materials and Methods: Thirty female adult albino rats (180-200 g) were divided into three groups (n=10): saline (0.9% NaCl, IP) was given to the control group, the cisplatin group: received (5 mg/kg/once a week IP) for 5 successive weeks, the RJ+Cis. group: received RJ (100 mg/kg/ day PO daily), and Cisplatin (5 mg/kg/once per week IP) for 5 successive weeks. At the end of the experiment, rats were sacrificed and their ovaries were isolated and used for biochemical analysis, molecular investigations and morphometric assessment as well as histological study. Moreover, blood samples were collected for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), Estradiol, progesterone and anti-mullerian hormone (AMH).Results: The current study clarified that RJ given to rats prior to cisplatin significantly increased the ovarian and uterine weights, in addition to follicular count at P˂0.05 compared to rats injected only with cisplatin. Moreover, it restored normal ovarian histological structure with a concurrent reduction in FSH, and LH levels, and increased AMH and ovarian hormone concentrations at P˂0.05 compared to cisplatin group. Also, RJ decreased the ovarian antioxidant/oxidative imbalance harmonized with significant suppression of inducible nitric oxide synthase and increase of quinone oxidoreductase 1 mRNA expression at P˂0.05 compared to cisplatin group.Conclusion: We concluded that RJ could alleviate mitochondrial-induced ovarian apoptosis caused by cisplatin via increasing anti-apoptotic Bcl2, and diminishing pro-apoptotic Bax with a concomitant increase of Mfn2 mRNA and protein expressions.

Objective(s): The current study aimed to assess cisplatin-mediated ovarian apoptosis in a rat model by Royal jelly (RJ). Materials and Methods: Thirty female adult albino rats (180-200 g) were divided into three groups (n=10): saline (0.9% NaCl, IP) was given to the control group, the cisplatin group: received (5 mg/kg/once a week IP) for 5 successive weeks, the RJ+Cis. group: received RJ (100 mg/kg/ day PO daily), and Cisplatin (5 mg/kg/once per week IP) for 5 successive weeks. At the end of the experiment, rats were sacrificed and their ovaries were isolated and used for biochemical analysis, molecular investigations and morphometric assessment as well as histological study. Moreover, blood samples were collected for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), Estradiol, progesterone and anti-mullerian hormone (AMH). Results: The current study clarified that RJ given to rats prior to cisplatin significantly increased the ovarian and uterine weights, in addition to follicular count at P˂0.05 compared to rats injected only with cisplatin. Moreover, it restored normal ovarian histological structure with a concurrent reduction in FSH, and LH levels, and increased AMH and ovarian hormone concentrations at P˂0.05 compared to cisplatin group. Also, RJ decreased the ovarian antioxidant/oxidative imbalance harmonized with significant suppression of inducible nitric oxide synthase and increase of quinone oxidoreductase 1 mRNA expression at P˂0.05 compared to cisplatin group. Conclusion: We concluded that RJ could alleviate mitochondrial-induced ovarian apoptosis caused by cisplatin via increasing anti-apoptotic Bcl2, and diminishing pro-apoptotic Bax with a concomitant increase of Mfn2 mRNA and protein expressions. [ABSTRACT FROM AUTHOR]

The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions.

Exposure to hypoxia has shown beneficial adjustments in different species, including silver catfish (Rhamdia quelen), especially in situations of aquatic contamination with pollutants such as manganese (Mn). Considering that hypoxia is seasonal in the natural aquatic environment, we decided to assess whether these adaptive mechanisms could be maintained when reoxygenation is established. Silver catfish acclimated to moderate hypoxia (~3 mg L-1, 41% O2 saturation) for 10 days and subsequently exposed to Mn (~8.1 mg L-1) for additional 10 days displayed lower (47%) Mn accumulation in the gills, and it was maintained (62.6%) after reoxygenation, in comparison to normoxia. Oxidative status in the gills allowed us to observe increased reactive species (RS) generation and protein carbonyl (PC) level together with decreased mitochondrial viability induced by Mn under normoxia. Inversely, while hypoxia per se was beneficial on RS generation and PC level, this acclimation was able to minimize Mn toxicity, as observed by the minor increase of RS generation and the minor reduction of mitochondrial viability, together with decreased PC level. Interestingly, after reoxygenation, part of the protective influences observed during hypoxia against Mn toxicity were maintained, as observed through a lower level of PC and higher mitochondrial viability in relation to the group exposed to Mn under normoxia. Only groups exposed to Mn under hypoxia showed increased activity of both catalase (CAT) and Na+/K+-ATPase in the gills, but, while CAT activity remained increased after reoxygenation, Na+/K+-ATPase activity was decreased by Mn, regardless of the oxygen level. Based on these outcomes, it is possible to propose that environment events of moderate hypoxia are able to generate rearrangements in the gills of silver catfish exposed to Mn, whose influence persists after water reoxygenation. These responses may be related to the adaptive development, reducing Mn toxicity to silver catfish.Moderate hypoxia generates rearrangements in the gills of Silver catfish, exerting beneficial and persistent protection against Mn toxicity. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effect of diethylhexylphthalate (DEHP) on testicular mitochondrial viability and lipid peroxidation as a possible novel mechanism of PEHP testicular toxicity and whether grape seed extract (GSE) beneficially influences the mitochondrial function in testes of rats exposed to diethylhexylphthalate (DEHP). Sixty male albino rats were divided into three groups (n = 20): group I: was used as a control, group II: received diethylhexylphthalate (DEHP) (500 mg/kg/day orally) alone for 30 days, and group III: received the same DEHP dose in combination with GSE (proanthocyanidins) (100 mg/kg body weight). DEHP administration significantly decreases the testicular mitochondrial viability, mRNA expression of androgen receptors (AR), testosterone hormone concentration, increases mRNA expression of INOS and as compared to control group. It also decreases reduced glutathione (GSH) concentration, glutathione reductase (GR), super oxide dismutase (SOD), Catalase activities and increases lipid peroxidation (LPO) and DNA fragmentation%. In synchronization, a substantial decrease of testicular & epididymal weight and volume which accompanied by considerable alteration of semen character. Grape seed extract (GSE) alleviates the toxic effects of DEHP by increasing the mitochondrial viability, decreases the lipid peroxidation, and increases the testicular antioxidant activity. Our results were confirmed by histopathological and immunhistochemical studies. [ABSTRACT FROM AUTHOR]

Background: Methyl mercury (MeHg), an important environmental toxicant is implicated in neurological disorders such as Hunter-Russell syndrome and Autism. Therefore, the present work is in search of new drugs that can alleviate MeHg toxicity. In this connection, Tagara, an ayurvedic drug is used for assessing its neuro protective effect against MeHg toxicity. Methods: In the present study, we assessed the phytochemical contents of Tagara by colorimetric and HPLC analyses. The neuroprotective effect of Tagara on MeHg induced neurotoxicity was measured in terms of viability by MTT assay and oxidative stress in terms of catalase activity, glutathione and thiobarbituric acid reactive substance levels. Further, the chelating effect of Tagara towards MeHg was performed to identify the molecular mechanism. Statistical analysis was done by statistical package for social sciences (SPSS) version 16.0. Results: The results demonstrated that Tagara contains significant amounts of phenols and flavonoids. Also, HPLC analysis of Tagara revealed the presence of essential oils such as hydroxyvalerenic and valerenic acids. Our results demonstrated that exposure of rat brain mitochondrial fractions to MeHg resulted in a dose dependent death in MTT assay and IC50 value was found to be 10 µM. However, a 250 µg dose of Tagara effectively prevented MeHg induced mitochondrial damage. The oxidative stress caused by MeHg results in elevated levels of reactive oxygen species as evidenced by elevated TBARS (Thiobarbituric acid-reactive substances) levels and diminished catalase enzyme activity and glutathione content. However, Tagara at 250 µg concentration offsets these alterations caused by MeHg. Further, Tagara also diminished GSH oxidation caused by MeHg, confirming its chelating effect, one of the molecular mechanisms that triggers protection against oxidative damage. Conclusion: Our results revealed that MeHg induced toxicity is predominantly mediated through oxidative stress mechanism and the propensity of Tagara to abolish such reactions. Hence, we propose that Tagara with a source of potential neuroprotectants may be a useful approach to alleviate MeHg associated neurotoxicity. [ABSTRACT FROM AUTHOR]

The present study evaluates the neuroprotective effect of Brahmi against methyl mercury (MeHg) toxicity. The results demonstrated that MeHg-decreased mitochondrial viability in MTT assay and IC50 value was found to be 2.5 μg/mL. However, Brahmi at 250 μg/mL concentration effectively prevented mitochondrial damage caused by MeHg in MTT assay. Our results also demonstrated MeHg significantly inhibited catalase enzyme activity, glutathione content and increased the level of thiobarbituric acid reactive substances in mitochondrial-enriched fractions of rat brain. These alterations were prevented by preincubation with Brahmi. In addition, Brahmi reverted glutathione level to normal that was depleted by MeHg, confirming its chelating effect, one of the molecular mechanisms that underlie protection against oxidative damage. Our study also focused on total phenolic and flavonoid contents of Brahmi, and it was found to contain significant amount of phenols and flavonoids. The presence of saponins was detected by HPLC which might be responsible for neuroprotection against MeHg. [ABSTRACT FROM AUTHOR]