Iftekhar Hassan

Ameliorative effect of riboflavin on the cisplatin induced nephrotoxicity and hepatotoxicity under photoillumination.

Cisplatin is a widely used anticancer drug. It is documented that it elicits major side effects like nephrotoxicity and hepatotoxicity due to oxidative stress forcing the patients to limit its clinical use in long term treatment. Riboflavin (vitamin B(2)) is a strong photosensitizer because it generates reactive oxygen species (ROS) upon photoillumination. We have tried to trap its photosensitizing property to ameliorate the cisplatin induced nephrotoxicity and hepatotoxicity in mice. They were treated with riboflavin and cisplatin separately as well as with their combination under photoilluminated condition. The status of major antioxidant enzymes, antioxidant proteins, functional markers, lipid peroxidation and protein oxidation was studied in liver, kidneys and serum samples of all the groups. Cisplatin treated group showed significantly compromised level of antioxidant enzymes and the proteins with higher extent of lipid and protein oxidation. Similar but less pronounced pattern was observed in the riboflavin treated group. The groups treated with the combination of cisplatin and riboflavin showed all the parameters tended towards normal levels in a dose dependent manner. Hence, it can be hypothesized that riboflavin shows ameliorative effect on the cisplatin induced nephrotoxicity and hepatotoxicity under the mentioned treatment conditions.

Riboflavin Ameliorates Cisplatin Induced Toxicities under Photoillumination

Background Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. Methods and Findings Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. Conclusion Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

Protein Misfolding and Aggregation in Alzheimer's Disease and Type 2 Diabetes Mellitus

In general, proteins can only execute their various biological functions when they are appropriately folded. Their amino acid sequence encodes the relevant information required for correct three-dimensional folding, with or without the assistance of chaperones. The challenge associated with understanding protein folding is currently one of the most important aspects of the biological sciences. Misfolded protein intermediates form large polymers of unwanted aggregates and are involved in the pathogenesis of many human diseases, including Alzheimers disease (AD) and Type 2 diabetes mellitus (T2DM). AD is one of the most prevalent neurological disorders and has worldwide impact; whereas T2DM is considered a metabolic disease that detrementally influences numerous organs, afflicts some 8% of the adult population, and shares many risk factors with AD. Research data indicates that there is a widespread conformational change in the proteins involved in AD and T2DM that form β-sheet like motifs. Although conformation of these β-sheets is common to many functional proteins, the transition from α-helix to β-sheet is a typical characteristic of amyloid deposits. Any abnormality in this transition results in protein aggregation and generation of insoluble fibrils. The abnormal and toxic proteins can interact with other native proteins and consequently catalyze their transition into the toxic state. Both AD and T2DM are prevalent in the aged population. AD is characterized by the accumulation of amyloid-β (Aβ) in brain, while T2DM is characterized by the deposition of islet amyloid polypeptide (IAPP, also known as amylin) within beta-cells of the pancreas. T2DM increases pathological angiogenesis and immature vascularisation. This also leads to chronic cerebral hypoperfusion, which results in dysfunction and degeneration of neuroglial cells. With an abundance of common mechanisms underpinning both disorders, a significant question that can be posed is whether T2DM leads to AD in aged individuals and the associations between other protein misfolding diseases.

White light-mediated Cu (II)–5FU interaction augments the chemotherapeutic potential of 5-FU: an in vitro study

Abstract5-Fluorouracil (5-FU) is a potent photosensitizer used in colon and rectal cancers. 5-FU on galvanostatic electrolysis or radiation-induced oxidation of aqueous solution yields N1–C5-linked dimmer hydrate of 5-FU. Copper is presently associated with chromatin; in cancer cells the concentration of copper is very high. It has been shown to be capable of mediating the action of several anticancer drugs through the production of reactive oxygen species (ROS). The objective of the present study is to determine the Cu (II)-mediated anticancer mechanism of 5-FU under photo-illumination as well as 5-FU alone. We have shown that a pro-oxidant action was enhanced when Cu (II) was used with 5-FU as compared to 5-FU alone. This may be due to the inhibition of dimerization of 5-FU when present in combination with Cu (II) under photo-illumination. It was also shown that 5-FU alone as well as in combination with Cu (II) was able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS. Moreover, the results of Fourier-transformed infrared spectra lead to the conclusion that the dimerization of 5-FU was inhibited when used in combination with Cu (II). It was due to the interaction of 5-FU with Cu (II). Hence, we propose that during chemoradiotherapy with 5-FU, the endogenous copper is mobilized by 5-FU, leading to the generation of ROS which cause oxidative stress and possibly cancer cell death by apoptosis.

Biogenic synthesis of Zinc oxide nanostructures from Nigella sativa seed: Prospective role as food packaging material inhibiting broad-spectrum quorum sensing and biofilm

Bacterial spoilage of food products is regulated by density dependent communication system called quorum sensing (QS). QS control biofilm formation in numerous food pathogens and Biofilms formed on food surfaces act as carriers of bacterial contamination leading to spoilage of food and health hazards. Agents inhibiting or interfering with bacterial QS and biofilm are gaining importance as a novel class of next-generation food preservatives/packaging material. In the present study, Zinc nanostructures were synthesised using Nigella sativa seed extract (NS-ZnNPs). Synthesized nanostructures were characterized hexagonal wurtzite structure of size ~24 nm by UV-visible, XRD, FTIR and TEM. NS-ZnNPs demonstrated broad-spectrum QS inhibition in C. violaceum and P. aeruginosa biosensor strains. Synthesized nanostructures inhibited QS regulated functions of C. violaceum CVO26 (violacein) and elastase, protease, pyocyanin and alginate production in PAO1 significantly. NS-ZnNPs at sub-inhibitory concentrations inhibited the biofilm formation of four-food pathogens viz. C. violaceum 12472, PAO1, L. monocytogenes, E. coli. Moreover, NS-ZnNPs was found effective in inhibiting pre-formed mature biofilms of the four pathogens. Therefore, the broad-spectrum inhibition of QS and biofilm by biogenic Zinc oxide nanoparticles and it is envisaged that these nontoxic bioactive nanostructures can be used as food packaging material and/or as food preservative.

Vitamin B2: A promising adjuvant in cisplatin based chemoradiotherapy by cellular redox management

Cancer has been a big challenge in the clinical research arena for many years. All the major anticancer drugs are either not effective or induce serious side effects. Cisplatin (CP) is one of the most valued anticancer drugs against various forms of cancer but it exerts many side effects often resulting in withdrawal of clinical usage during long-term chemotherapy. Thus, increasing the efficacy of the drugs and minimizing deleterious side effects is needed. Vitamins like riboflavin (RF) are promising under photodynamic therapy in this aspect because of its potential as an efficient adjuvant confirmed in many cancer cell lines and animal-based studies. It has been found to alleviate CP-induced side effects significantly under photoillumination in mice. As CP exerts most of its toxic effects by oxidative and nitrosative stress; clubbing ribophototherapy with chemotherapy involving CP can shift the redox status favoring better cancer treatment. This strategy can not only increase the average life span of the cancer patients but also improve their quality of life significantly. However, cancer is still considered as a disease of genetic and metabolic disorders; hence, attacking both aspects of the disease can give better results as compared to contemporary treatment modalities.

Recent updates on the dynamic association between oxidative stress and neurodegenerative disorders

Free radicals are generated as byproduct of our body metabolism, and their adverse effect on normal functioning of our body is prevented by bodys own antioxidant machinery. Any perturbation in the defense mechanism of antioxidants inside body, its abnormal production or its induction from environment to our body lead to serious threats and is responsible for the development of various neurodegenerative disorders (NDDs). Perturbed antioxidants result in sensory and functional impairments in neuronal cells, which in turn cause NDDs. Free radical attack on neuronal cells plays a catastrophic role in NDDs. Impaired metabolism and generation of excessive reactive oxygen species also lead to a range of NDDs. Free radical induced toxicity is responsible for DNA injury, protein degradation, damage to tissue inflammation and cell death. Besides various genetic and environmental factors, free radical induced oxidative stress is also a major cause of NDDs. Application of upstream and downstream antioxidant therapy to counter oxidative stress can be an effective option in alteration of any neuronal impairment besides free radical scavenging. In the present manuscript, we have presented a comprehensive update on the symptoms, causes and cures of NDDs in relation with their dynamic association with oxidative stress.

Cisplatin-induced neurotoxicity in vivo can be alleviated by riboflavin under photoillumination.

Cisplatin (CP)-induced neurotoxicity is one of the major clinical problems in CP-based chemoradiotherapy, leading to its discontinuation depending upon their severity. In the present investigation, the photosensitizing property of riboflavin (RF) has been used to ameliorate the CP-induced neurotoxicity. According to dosing plan, the healthy mice were given RF, CP, and their combinations under photoillumination with their controls without any light exposure. After the treatment, antioxidant enzymes, cellular reductants, glutathione-S-transferase, brain markers, and oxidation products were assessed besides histopathology in their brain samples. These parameters revealed that RF ameliorates CP-induced neurotoxicity in a dose-dependent manner under photoillumination. Hence, inclusion of RF in CP-based chemoradiotherapy can be an effective strategy to counter CP-induced neurotoxicity.

Novel aspect of chemophototherapy in treatment of cancer

The present review deals with the genetic implications of reactive oxygen species (ROS) to enhance horizons of chemophototherapy toward novel approaches for the treatment of various cancers. ROS are species of oxygen which are in a more reactive state than molecular oxygen. ROS play essential roles in vivo such as redox regulation, gene expression, immune response and many other cellular events. ROS generated by anticancer drugs during chemophototherapy may be associated with the activation of signal molecules like PKC, transcription factor NF-kappaB as well as destabilization of mitochondrial membrane inducing the release of apoptosis inducing agents like cytochrome c, resulting in toxicity to cancer cells. Thus, we suggest that anticancer drugs on exposure to light may generate oxidative stress following Fenton-like reaction generating hydroxyl radical. This may get on specific cell cycle receptors which may lead to cell cycle arrest and subsequently cytotoxic death of cancer cells.

In vitro pro-oxidant action of Methotrexate in presence of white light

Methotrexate (MTX) an anti-cancer drug as well as a photosensitizer is able to generate reactive oxygen species (ROS). Cu (II) is present associated with chromatin in cancer cells and has been shown to be capable of mediating the action of several anti-cancer drugs through production of ROS. The objective of the present study is to determine Cu (II) mediated anti-cancer mechanism of MTX under photoilluminated condition as well as alone, using alkaline single cell gel electrophoresis (comet assay). We have shown that cellular DNA breakage was enhanced when Cu (II) is used with MTX as compared to MTX alone. It is also shown that MTX alone as well as in combination with Cu (II) is able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS but the pattern of inhibition was differential as was also demonstrated by plasmid nicking assay. Thus, we can say that MTX exhibit pro-oxidant action in presence of white light which gets elevated in presence of Cu (II). Hence, we propose that the mobilization of endogenous copper is possibly involved in killing of cancer cells by MTX during chemo-radio therapy besides acting as antifolate.