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Diabetes is embracing the human population in logarithmic fashion both in developed as well as developing countries. Aldose reductase is one of the important enzymes of polyol pathway of sugar metabolism in humans. Aldose reductase inhibition has been identified as one of the important target for developing novel antidiabetic agents. In this report, we present an effective synthesis of 7-(substituted phenyl) chromeno-pyrano [2,3-d]pyrimidine-6,8,10-(7H,9H,11H)-trione derivatives and demonstrate their aldose reductase inhibition potential in order to identify novel schemes for finding putative aldose reductase inhibitors. The antioxidant activity of all the synthesized compounds with negligible toxicity demonstrates the biological efficacy of the synthesized compounds. The in silico molecular docking and structural analysis of docked poses conducted in the current investigation sheds light on the structural rationale of the observed aldose reductase inhibition by all the newly synthesized compounds.

Exposure to ionizing radiation (IR) is a common phenomenon during medical diagnosis and treatment. IRs are deleterious because cellular exposure to IR can cause a series of molecular events that may lead to oxidative stress and macromolecular damage. Radiation protection is therefore essential and significant for improving safety during these procedures. Over decades several antioxidant molecules have been screened to explore their potential as radio-protectors with little success. Therefore, the current study was carried out to confirm the role of uric acid (UA)—a putative antioxidant molecule in radioprotection using radio-resistant insect Drosophila and human dermal fibroblast (HDF) cells. Here, we demonstrate the depleted levels of UA in the mutant flies of Drosophila melanogaster-rosy and by targeting xanthine oxidase (XO an enzyme involved in UA metabolism), through maintaining flies on an allopurinol mixed diet. Allopurinol is a drug that reduces UA levels by inhibiting XO; it reduces the survival percentage in D. melanogaster compared to wild type flies following gamma irradiation at a dose of 1000 Gy. Enzymatic antioxidants such as superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx) and levels of non-enzymatic antioxidants were measured to evaluate the importance of UA. The results indicate that lack of UA reduces the total antioxidant capacity. The activity of SOD was lowered in male flies. Furthermore, we show that supplementation of UA to HDFs cells in media improved their survival rate following gamma irradiation (2 Gy). From the present study we conclude that UA is a potent antioxidant molecule present in high levels among insects. Also, it appears that UA contributes to the radiation resistance of Drosophila flies. Hence, UA emerges as a promising molecule for mitigating radiation-induced oxidative damage in higher organisms.

Background: Tragia involucrata L. has been used in Indian traditional medicine since centuries to treat various ailments. The plant remains unexplored for its radioprotective properties and hence the present study. Objective: The main objective of the study is to ascertain the radioprotective effects of T. involucrata methanolic extract (TME) in Swiss albino mice against whole-body gamma radiation. Materials and Methods: The acute toxicity of TME was evaluated. The optimal protective dose of TME against radiation-induced mortality in mice was determined by survival analysis using the Kaplan–Meier curves. To understand the mechanism of radioprotection, TME was tested for hematological changes and antioxidant levels in mice by injecting100 mg/kg body weight intraperitoneally for 5 days and irradiated with a sublethal dose of 6 Gy gamma radiation. Results: The lethal dose 50%/of TME was about 645.65 mg/kgbw. The pretreatment of mice with 100 mg/kgbw of TME increased its survivability to 30% compared with the radiation control group and hence is considered as a radioprotective dose. The lethal dose 50%/30% of the irradiation alone group was found to be 9 Gy and 10.35 Gy for the TME + irradiation group. Hence, the dose reduction factor was about 1.15. The radiation decreased the hematological parameters in the blood, but on pretreatment with TME (100 mg/kgbw), increase in levels was noted. The antioxidant enzyme levels in the mice liver homogenate were found to be replenished in the test group compared with the radiation control. Conclusion: The present study indicates the protective role of TME against gamma radiation-induced mortality and oxidative stress. Hence, it is proposed as a candidate for radioprotection.

This study examined the effect of lethal (4.5 μg/l) and sublethal (0.45 μg/l) malathion levels on oxidative stress responses of the freshwater edible fish, Labeo rohita. Fish were exposed to lethal (1-4 days) and sublethal (1, 5, 10, and 15 days) periods. In the present study, catalase and protease activity, hydrogen peroxide, malondialdehyde, protein carbonyls, and free amino acids levels increased in the gill, liver, and kidney tissues of fish exposed to lethal and sublethal concentrations of malathion except protein content. Time- and concentration-dependent induction/reduction of the above parameters by lethal and sublethal concentrations of malathion was observed in the tissues (the gill, liver, and kidney) of L. rohita. Thus, the results clearly infer oxidative damage and decline in antioxidant defense due to malathion-induced oxidative stress.

Mitochondria are at the heart of all cellular processes as they provide the majority of the energy needed for various metabolic processes. Nitric oxide has been shown to have numerous roles in the regulation of mitochondrial function. Mitochondria have enormous pools of glutathione (GSH≈5-10 mM). Nitric oxide can react with glutathione to generate a physiological molecule, S-nitrosoglutathione (GSNO). The impact GSNO has on mitochondrial function has been intensively studied in recent years, and several mitochondrial electron transport chain complex proteins have been shown to be targeted by GSNO. In this study we investigated the effect of GSNO on mitochondrial function using normal rat proximal tubular kidney cells (NRK cells). GSNO treatment of NRK cells led to mitochondrial membrane depolarization and significant reduction in activities of mitochondrial complex IV and manganese superoxide dismutase enzyme (MnSOD). MnSOD is a critical endogenous antioxidant enzyme that scavenges excess superoxide radicals in the mitochondria. The decrease in MnSOD activity was not associated with a reduction in its protein levels and treatment of NRK cell lysate with dithiothreitol (a strong sulfhydryl-group-reducing agent) restored MnSOD activity to control values. GSNO is known to cause both S-nitrosylation and S-glutathionylation, which involve the addition of NO and GS groups, respectively, to protein sulfhydryl (SH) groups of cysteine residues. Endogenous GSH is an essential mediator in S-glutathionylation of cellular proteins, and the current studies revealed that GSH is required for MnSOD inactivation after GSNO or diamide treatment in rat kidney cells as well as in isolated kidneys. Further studies showed that GSNO led to glutathionylation of MnSOD; however, glutathionylated recombinant MnSOD was not inactivated. This suggests that a more complex pathway, possibly involving the participation of multiple proteins, leads to MnSOD inactivation after GSNO treatment. The major highlight of these studies is the fact that dithiothreitol can restore MnSOD activity after GSNO treatment. To our knowledge, this is the first study showing that MnSOD activity can be reversibly regulated in vivo, through a mechanism involving thiol residues.