Reestablishment Of Redox Homeostasis Research Articles

Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease. Recently approved molecular/gene treatments do not solve the downstream inflammation-linked pathophysiological issues such that supportive therapies are required to improve therapeutic efficacy and patients' quality of life. Over the years, a plethora of bioactive natural compounds have been used for human healthcare. Among them, plumbagin, a plant-derived analog of vitamin K3, has shown interesting potential to counteract chronic inflammation with potential therapeutic significance.In this work we evaluated the effects of plumbagin on DMD by delivering it as an oral supplement within food to dystrophic mutant of the fruit fly Drosophila melanogaster and mdx mice. In both DMD models, plumbagin show no relevant adverse effect. In terms of efficacy plumbagin improved the climbing ability of the dystrophic flies and their muscle morphology also reducing oxidative stress in muscles. In mdx mice, plumbagin enhanced the running performance on the treadmill and the muscle strength along with muscle morphology. The molecular mechanism underpinning these actions was found to be the activation of nuclear factor erythroid 2-related factor 2 pathway, the re-establishment of redox homeostasis and the reduction of inflammation thus generating a more favorable environment for skeletal muscles regeneration after damage.Our data provide evidence that food supplementation with plumbagin modulates the main, evolutionary conserved, mechanistic pathophysiological hallmarks of dystrophy, thus improving muscle function in vivo; the use of plumbagin as a therapeutic in humans should thus be explored further.

Polyherbal decoction modulates redox homeostasis during Malachite green induced metabolic stress in <em>Saccharomyces cerevisiae</em>

Malachite green (MG) is aquatic pollutant that induces oxidative stress when comes in contact with the living organisms. In Saccharomyces cerevisiae, MG produces intracellular reactive oxygen species (ROS) and these ROS disturb redox homeostasis and cellular functions leading to early cell death. Exogenous supply of natural antioxidants containing polyherbal decoction may play a crucial role in re-establishment of redox homeostasis by ensuring the cell survival. Exposure of MG to Saccharomyces cerevisiae resulted in a significant decrease (97.8%) in colony forming units (CFU). An Ayurvedic polyherbal formulation ‘Vayasthapana Rasayana’ (VR) which contains natural antioxidants from plants viz. Terminalia chebula, Clitoria ternatea, Boerhaavia diffusa, Centella asiatica, Phyllanthus emblica, Asparagus racemossus and Tinospora cordifolia at 1.0 mg/mL concentration could arrest the oxidative stress during MG exposure. Levels of ROS elevated up to 67.3% on MG exposure; while VR supplementation reduced it by 54.7%. MG induced cellular apoptosis in 38% and necrosis in 27% cells, while VR augmentation reduced it to 8%. Activities of antioxidant enzymes like catalase, superoxide dismutase and glutathione peroxidase in MG exposed cells were induced by 408, 144 and 140%, respectively, whereas, VR supplementation lowered the expressions to 102, 57 and 111%, respectively. Induction in caspases 3/7 activity was also found to be reduced by 65.39% after VR augmentation. Similarly, VR modulated activities of oxido-reductases like lignin peroxidase, laccase, NADH-DCIP reductase and MG reductase. VR supplementation also maintained the MG utilization potential of S. cerevisiae up to 20th exposure cycle which was otherwise arrested to 8th cycle. The treatment also decreased the ROS accumulation and nuclear damage, restoring the cell viability up to 94% and retained normal growth dynamics. Thus, VR supplementation could significantly decrease oxidative stress, enhance cell viability and ultimately protect the dying S. cerevisiae cells during MG exposure.

Exogenous proline mitigates toxic effects of cadmium via the decrease of cadmium accumulation and reestablishment of redox homeostasis in Brassica juncea

BackgroundAs a vital osmoticum, proline has an important role in enhancing the tolerance of plants to environmental stress. It is unclear whether the application of exogenous proline can improve the tolerance of Brassica juncea to cadmium (Cd).ResultsThis study investigated the effects of different concentrations of proline (20, 40, 60, 80, and 100 mg/L) under Cd stress at different times (0 d, 2 d, and 7 d) on the growth and physiology of B. juncea. Treatment with exogenous proline not only increased the content of proline in B. juncea but also alleviated Cd-induced seedling growth inhibition via the maintenance of higher photosynthetic pigment content and cell viability and a decrease in the content of Cd. Moreover, it increased the activities of antioxidant enzymes and the glutathione/glutathione disulfide ratio to reduce the accumulation of reactive oxygen species. Compared with other concentrations, 60 mg/L of exogenous proline was the most effective at mitigating Cd toxicity in B. juncea.ConclusionsExogenous proline treatment enhanced the tolerance to Cd via a decrease in Cd accumulation and reestablishment of the redox homeostasis in B. juncea.

Reestablishment of Redox Homeostasis in the Nociceptive Primary Afferent as a Mechanism of Antinociception Promoted by Mesenchymal Stem/Stromal Cells in Oxaliplatin-Induced Chronic Peripheral Neuropathy.

Painful neuropathy is a common adverse effect of oxaliplatin (OXL), a platinum-derivative chemotherapeutic agent. Oxidative stress and mitochondrial dysfunction are key factors contributing to the development of OXL-induced peripheral neuropathy (OIPN). Based on the antioxidant and antinociceptive properties of mesenchymal stem/stromal cells (MSC), the present study tested the hypothesis that MSC induce antinociceptive effects during OIPN by promoting regulation of redox environment and mitochondrial homeostasis in the nociceptive primary afferents. C57Bl/6 mice submitted to the OXL-chronic neuropathy induction protocol by repeated intravenous administration of OXL (1 mg/kg) were evaluated to determine the paw mechanical and thermal nociceptive thresholds using the von Frey filaments and cold plate tests, respectively. Two weeks after the neuropathy induction, mice were treated with bone marrow-derived MSC (1 × 106), vehicle, or gabapentin (GBP, 70 mg/kg). Four weeks later, mitochondrial morphology, gene expression profile, and oxidative stress markers in the sciatic nerve and dorsal root ganglia (DRG) were evaluated by transmission electron microscopy, RT-qPCR, and biochemical assays, respectively. OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia. The behavioral painful neuropathy was completely reverted by a single administration of MSC, while the daily treatment with GBP induced only a short-lived antinociceptive effect. The ultrastructural analysis of the sciatic nerve and DRG of OIPN mice revealed a high proportion of atypical mitochondria in both myelinated and unmyelinated fibers. Importantly, this mitochondrial atypia was strongly reduced in MSC-treated neuropathic mice. Moreover, MSC-treated neuropathic mice showed upregulation of Sod and Nrf2 mRNA in the sciatic nerve and DRG. In line with this result, MSC reduced markers of nitrosative stress and lipid peroxidation in the sciatic nerve and DRG from OIPN mice. Our data suggest that the reestablishment of redox homeostasis in the nociceptive primary afferents is a mechanism by which MSC transplantation reverts the OXL-induced chronic painful neuropathy.

Nitric Oxide Is Required for Melatonin-Enhanced Tolerance against Salinity Stress in Rapeseed (Brassica napus L.) Seedlings.

Although melatonin (N-acetyl-5-methoxytryptamine) could alleviate salinity stress in plants, the downstream signaling pathway is still not fully characterized. Here, we report that endogenous melatonin and thereafter nitric oxide (NO) accumulation was successively increased in NaCl-stressed rapeseed (Brassica napus L.) seedling roots. Application of melatonin and NO-releasing compound not only counteracted NaCl-induced seedling growth inhibition, but also reestablished redox and ion homeostasis, the latter of which are confirmed by the alleviation of reactive oxygen species overproduction, the decreases in thiobarbituric acid reactive substances production, and Na+/K+ ratio. Consistently, the related antioxidant defense genes, sodium hydrogen exchanger (NHX1), and salt overly sensitive 2 (SOS2) transcripts are modulated. The involvement S-nitrosylation, a redox-based posttranslational modification triggered by NO, is suggested. Further results show that in response to NaCl stress, the increased NO levels are strengthened by the addition of melatonin in seedling roots. Above responses are abolished by the removal of NO by NO scavenger. We further discover that the removal of NO does not alter endogenous melatonin content in roots supplemented with NaCl alone or together with melatonin, thus excluding the possibility of NO-triggered melatonin production. Genetic evidence reveals that, compared with wild-type Arabidopsis, the hypersensitivity to NaCl in nia1/2 and noa1 mutants (exhibiting null nitrate reductase activity and indirectly reduced endogenous NO level, respectively) cannot be rescued by melatonin supplementation. The reestablishment of redox homeostasis and induction of SOS signaling are not observed. In summary, above pharmacological, molecular, and genetic data conclude that NO operates downstream of melatonin promoting salinity tolerance.

Methane alleviates copper-induced seed germination inhibition and oxidative stress in Medicago sativa.

Recent results discovered the protective roles of methane (CH4) against oxidative stress in animals. However, the possible physiological roles of CH4 in plants are still unknown. By using physiological, histochemical and molecular approaches, the beneficial role of CH4 in germinating alfalfa seeds upon copper (Cu) stress was evaluated. Endogenous production of CH4 was significantly increased in Cu-stressed alfalfa seeds, which was mimicked by 0.39mM CH4. The pretreatment with CH4 significantly alleviated the inhibition of seed germination and seedling growth induced by Cu stress. Cu accumulation was obviously blocked as well. Meanwhile, α/β amylase activities and sugar contents were increased, all of which were consistent with the alleviation of seed germination inhibition triggered by CH4. The Cu-triggered oxidative stress was also mitigated, which was confirmed by the decrease of lipid peroxidation and reduction of Cu-induced loss of plasma membrane integrity in CH4-pretreated alfalfa seedlings. The results of antioxidant enzymes, including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (POD) total or isozymatic activities, and corresponding transcripts (APX1/2, Cu/Zn SOD and Mn-SOD), indicated that CH4 reestablished cellular redox homeostasis. Further, Cu-induced proline accumulation was partly impaired by CH4, which was supported by the alternation of proline metabolism. Together, these results indicated that CH4 performs an advantageous effect on the alleviation of seed germination inhibition caused by Cu stress, and reestablishment of redox homeostasis mainly via increasing antioxidant defence.

Hydrogen-rich water confers plant tolerance to mercury toxicity in alfalfa seedlings

In this report, the effect of hydrogen-rich water (HRW), which was used to investigate the physiological roles of hydrogen gas (H2) in plants recently, on the regulation of plant adaptation to mercury (Hg) toxicity was studied. Firstly, we observed that the exposure of alfalfa seedlings to HgCl2 triggered production of reactive oxygen species (ROS), growth stunt and increased lipid peroxidation. However, such effects could be obviously blocked by HRW. Meanwhile, significant decreases in the relative ion leakage and Hg accumulation were observed. Hg-induced increases in total and isozymatic activities of superoxide dismutase (SOD) were significantly reversed by HRW. Further results suggested that HRW-induced the activities of guaiacol peroxidase (POD) and ascorbate peroxidase (APX), two hydrogen peroxide-scavenging enzymes, was at transcriptional levels. Meanwhile, obvious increases of the ratios of reduced/oxidized glutathione (GSH), homoglutathione (hGSH), and ascorbic acid (AsA) and corresponding gene expression were consistent with the decreased oxidative damage in seedling roots. In summary, the results of this investigation indicated that HRW was able to alleviate Hg toxicity in alfalfa seedlings by (i) alleviating growth stunt and reducing Hg accumulation, and (ii) avoidance of oxidative stress and reestablishment of redox homeostasis.