Ferric Nitrilotriacetate Research Articles

Punicalagin Ameliorating Renal Cell Tumors Against N-Diethylnitrosamine-initiated Iron Nitrilotriacetate-induced Carcinogenesis

Background Renal cell carcinoma, the most prominent kind of adult kidney cancer, lacks early warning symptoms, leading to metastases at the time of diagnosis. Renal cell carcinoma begins with N-diethylnitrosamine (DEN) and is accelerated by ferric nitrilotriacetate (Fe-NTA), which may be a good research model for renal cell carcinoma. Purpose This study was designed to unveil the protective potential of punicalagin against renal cell tumors induced by Fe-NTA in male mice. Methods Renal cancer initiation was achieved through a single intraperitoneal injection of DEN (200 mg/kg body weight (b.wt.)), followed by promotion using Fe-NTA (9 mg Fe/kg b.wt. intraperitoneally) administered twice weekly over 16 weeks. Simultaneously, mice were subjected to punicalagin (10 mg/kg b.wt.) for an uninterrupted 16-week duration. The chemopreventive efficacy of punicalagin was assessed by evaluating antioxidant activities, oxidative stress markers, renal function parameters, histopathological examinations, and immunohistochemical analyses. Results Results showed a significant reduction in DEN and Fe-NTA-mediated lipid peroxidation, concurrent with the amelioration of renal function, as reflected by diminished levels of blood urea nitrogen, creatinine, and kidney injury molecule-1 in punicalagin-treated mice. Furthermore, punicalagin restored the renal antioxidant parameters like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione in DEN and Fe-NTA-treated mice. Further, it was observed that punicalagin reduces the expression of 8-hydroxy-2′-deoxyguanosine (levels and 4-hydroxy-2-nonenal-modified protein adducts within the kidney tissue. Conclusion These findings were further substantiated by histological examinations. Our current findings indicate that punicalagin might be a potential contender for preventing renal cancer, likely due to its capacity to reduce oxidative stress in laboratory animals.

Continuous flow operation of solar photo-Fenton fused with NaOCl as a novel tertiary treatment

A novel strategy based on solar photo-Fenton mediated by ferric nitrilotriacetate (Fe3+-NTA) combined with NaOCl in continuous flow mode for wastewater reclamation has been studied. Escherichia coli (E. coli) inactivation attained ≥ 5 log10-units, meeting the most restrictive EU 2020/741 target (10 CFU/100 mL), and 75% of organic microcontaminant total load was removed. As a remarkable finding, trihalomethanes (THMs) concentration was insignificant, complying by far with the Italian legislation limit. To attain these results, first the effect of liquid depth on E. coli inactivation and imidacloprid (IMD) removal from spiked municipal effluents was evaluated in continuous flow pilot-scale raceway pond reactors at 60-min hydraulic residence time with low reagent concentrations (0.10 mM Fe3+-NTA, 0.73 mM H2O2 and 0.13 mM NaOCl). Disinfection was due to the bactericidal effect of chlorine. In contrast, liquid depth notably influenced microcontaminant removal, highlighting that operation at 10-cm liquid depth allows achieving treatment capacities higher than at 5 cm (16.50 vs 28.20 mg IMD/m2∙day). Next, the monitoring of THMs was carried out to evaluate the generation and degradation of disinfection by-products, along with the removal of actual microcontaminants. These promising results draw attention to the treatment potential and open the way for its commercial application.

Continuous solar photo-Fenton for wastewater reclamation in operational environment at demonstration scale

For the first time, a continuous flow solar photo-Fenton demonstration plant has been assessed for wastewater reclamation according to the EU 2020/741 regulation. The treated water qualities achieved under two operating strategies (acidic and neutral pH) in a 100-m2 raceway pond reactor were explored in terms of liquid depth, iron source, reagent concentrations, and hydraulic residence time over three consecutive days of operation. The results obtained at acidic pH showed removal percentages of contaminants of emerging concern (CECs) > 75% and water quality classes B, C and D according to EU regulation at both assessed operating conditions, with treatment capacities up to 1.92 m3 m-2 d-1. At neutral pH with ferric nitrilotriacetate (Fe3+-NTA), 50% of CEC removal and only water quality class D were achieved with the most oxidizing condition assessed, giving a treatment capacity of 0.80 m3 m-2 d-1. The treatment capacities obtained in this work, which have never been achieved with solar water treatments, demonstrate the potential of this technology for commercial-scale application.

Mechanistic modeling of solar photo-Fenton with Fe3+-NTA for microcontaminant removal

This work presents, for the first time, a mechanistic model of the solar photo-Fenton process with ferric nitrilotriacetate (Fe3+-NTA), the most cost-effective iron source for microcontaminant removal at neutral pH. The model was developed in three stages, considering the thermal decomposition of Fe3+-NTA, the contribution of temperature on Fenton-like reactions and the effect of the photon absorption of Fe3+-NTA on photochemical reactions. To determine the kinetic parameters, the imidacloprid degradation data (100 µg L−1) obtained at lab scale with 1.47 mM of H2O2 and 0.1 mM of Fe3+-NTA at different temperatures, UVA irradiances and liquid depths were used. The model was successfully validated in raceway pond reactors, changing the scale from 0.84 L to 80 L. According to model predictions, more than 90% of microcontaminant removal could be attained in 30 min operating the photoreactor with liquid depths of 15 cm and 60 cm in winter and summer, respectively.

Hepatoprotective Potential of Aqueous Extract of Hibiscus rosasinensis and Butea monosperma against Fe-NTA induced Hepatotoxicity in Rats

Hibiscus rosasinensis and Butea monosperma have been traditionally claimed to be protective against liver injury. However, the hepatoprotective effect against iron overload is not yet validated scientifically. The present study was undertaken to evaluate the possible ameliorating effect of aqueous extract of Hibiscus rosasinensis (AQEHR) and Butea monosperma (AQEBM) against ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in rats. After extraction, total phenolics and flavonoids content of AQEHR and AQEBM were estimated. Further, antioxidant effect followed by hepatoprotective efficacy of AQEHR and AQEBM were evaluated against chronic iron overload by administering Fe-NTA for 8 successive days to rats in increasing order of doses from 6-15mg Fe/kg. Treatments with both the extracts were started 3 days before the administration of iron and together with iron administration for 8 days. Level of liver function tests, triglycerides, protein, and lipid were recorded. Oxidative biomarkers and histopathology were performed to find out the level of protection by extracts. AQEBM contains a high amount of total phenolic and flavonoids contents and exhibited potent antioxidant effects in all assays. Supplementation of both the extract showed hepatoprotective effect by amelioration of biochemical changes and oxidative biomarkers. AQEBM possesses a higher amount of phenolic components and exhibited better therapeutic potential than AQEHR.

Is Glyceryl Trinitrate, a Nitric Oxide Donor Responsible for Ameliorating the Chemical-Induced Tissue Injury In Vivo?

Oxidative stress induced by well-known toxins including ferric nitrilotriacetate (Fe-NTA), carbon tetrachloride (CCl4) and thioacetamide (TAA) has been attributed to causing tissue injury in the liver and kidney. In this study, the effect of glyceryl trinitrate (GTN), a donor of nitric oxide and NG-nitroarginine methyl ester (l-NAME), a nitric oxide inhibitor on TAA-induced hepatic oxidative stress, GSH and GSH-dependent enzymes, serum transaminases and tumor promotion markers such as ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation in rats were examined. The animals were divided into seven groups consisting of six healthy rats per group. The six rats were injected intraperitoneally with TAA to evaluate its toxic effect, improvement in its toxic effect if any, or worsening in its toxic effect if any, when given in combination with GTN or l-NAME. The single necrogenic dose of TAA administration caused a significant change in the levels of both hepatic and serum enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (GGT), glucose 6-phosphate dehydrogenase (G6PD), alanine aminotransferase (AST) and aspartate aminotransferase (ALT). In addition, treatment with TAA also augmented malondialdehyde (MDA), ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation in rats liver. Concomitantly, TAA treatment depleted the levels of GSH. However, most of these changes were alleviated by the treatment of animals with GTN dose-dependently. The protective effect of GTN against TAA was also confirmed histopathologically. The present data confirmed our earlier findings with other oxidants including Fe-NTA and CCl4. The GTN showed no change whatsoever when administered alone, however when it was given along with TAA then it showed protection thereby contributing towards defending the role against oxidants-induced organ toxicity. Overall, GTN may contribute to protection against TAA-induced oxidative stress, toxicity, and proliferative response in the liver, according to our findings.

BRCA1 haploinsufficiency promotes chromosomal amplification under Fenton reaction-based carcinogenesis through ferroptosis-resistance

Germline-mutation in BRCA1 tumor suppressor gene is an established risk for carcinogenesis not only in females but also in males. Deficiency in the repair of DNA double-strand breaks is hypothesized as a responsible mechanism for carcinogenesis. However, supporting data is insufficient both in the mutation spectra of cancers in the patients with BRCA1 germline-mutation and in murine knockout/knock-in models of Brca1 haploinsufficiency. Furthermore, information on the driving force toward carcinogenesis in BRCA1 mutation carriers is lacking. Here we applied Fenton reaction-based renal carcinogenesis to a rat heterozygously knockout model of BRCA1 haploinsufficiency (mutant [MUT] model; L63X/+). Rat MUT model revealed significant promotion of renal cell carcinoma (RCC) induced by ferric nitrilotriacetate (Fe-NTA). Array-based comparative genome hybridization of the RCCs identified significant increase in chromosomal amplification, syntenic to those in breast cancers of BRCA1 mutation carriers, including c-Myc, in comparison to those in the wild-type. Subacute-phase analysis of the kidney after repeated Fe-NTA treatment in the MUT model revealed dysregulated iron metabolism with mitochondrial malfunction assessed by expression microarray and electron microscopy, leading to renal tubular proliferation with iron overload. In conclusion, we for the first time demonstrate that biallelic wild-type BRCA1 provides more robust protection for mitochondrial metabolism under iron-catalyzed oxidative stress, preventing the emergence of neoplastic cells with chromosomal amplification. Our results suggest that oxidative stress via excess iron is a major driving force for carcinogenesis in BRCA1 haploinsufficiency, which can be a target for cancer prevention and therapeutics.

A new solar photo-Fenton strategy for wastewater reclamation based on simultaneous supply of H2O2 and NaOCl

This study presents, for the first time, the concurrent supply of the oxidants H2O2 and NaOCl in solar-driven Fenton-like processes at neutral pH with ferric nitrilotriacetate (Fe3+-NTA) for wastewater reclamation. Simultaneous Escherichia coli (E. coli) inactivation and the removal of the antibiotic sulfamethoxazole (SMX) at 50 μg/L in municipal effluents were investigated in 5-cm deep raceway pond reactors. First, the individual effects of reagent concentrations (1.47, 2.94 and 4.41 mM for H2O2; 0.134, 0.269 and 0.403 mM for NaOCl; 0.1 and 0.2 mM for Fe3+-NTA) on the economic efficiency (in terms of mass of SMX eliminated per Euro and per hour to attain complete E. coli inactivation and more than 50% of SMX removal) were considered. The highest economic efficiencies were 141 mgSMX/€·h with H2O2 and 222 with NaOCl, the reaction times being 105 and 60 min, respectively. Second, a new strategy for solar photo-Fenton with the combination of the most cost-effective conditions (1.47 mM H2O2 – 0.134 mM NaOCl – 0.1 mM Fe3+-NTA) was carried out in secondary effluents from two treatment plants with different technologies. Economic efficiency was substantially affected by wastewater composition, ranging from 178 to 1131 mgSMX/€·h with treatment times between 60 and 10 min, significantly improving the reported results for conventional solar photo-Fenton to date.

The Role of Ferric Nitrilotriacetate in Renal Carcinogenesis and Cell Death: From Animal Models to Clinical Implications.

Simple SummaryIron is essential for cellular growth and survival. As a consequence, iron deficiency causes pleiotropic effects on the organism, while iron overload is also deleterious by means of oxidative tissue injury, which causes hepatic cirrhosis, diabetes mellitus, and cardiomyopathy in humans. Non-heme iron comprises ferric ion (Fe(III)), which is much more prominent in the transferrin, ferritin, or labile iron pool than the ferrous ion (Fe(II)); in contrast, ferrous ion yields more reactive oxygen species (ROS) than ferric ion does. In rodents, ferric nitrilotriacetate (Fe-NTA) elicits hepatic and renal oxidized lipids via a glutathione-cycle-dependent iron reduction that eventually causes renal cell carcinoma (RCC). In addition to iron-mediated carcinogenesis, ferroptosis is triggered by the iron-dependent accumulation of lipid peroxidation to lethal levels. Here, the mechanisms of iron- and ROS-mediated RCC and the therapeutic possibility of ferroptosis are discussed.Iron is essential for cellular growth, and various ferroproteins and heme-containing proteins are involved in a myriad of cellular functions, such as DNA synthesis, oxygen transport, and catalytic reactions. As a consequence, iron deficiency causes pleiotropic effects, such as hypochromic microcytic anemia and growth disturbance, while iron overload is also deleterious by oxidative injury. To prevent the generation of iron-mediated reactive oxygen species (ROS), ferritin is synthesized to store excess iron in cells that are consistent with the clinical utility of the serum ferritin concentration to monitor the therapeutic effect of iron-chelation. Among the animal models exploring iron-induced oxidative stress, ferric nitrilotriacetate (Fe-NTA) was shown to initiate hepatic and renal lipid peroxidation and the development of renal cell carcinoma (RCC) after repeated intraperitoneal injections of Fe-NTA. Here, current understanding of Fe-NTA-induced oxidative stress mediated by glutathione-cycle-dependent iron reduction and the molecular mechanisms of renal carcinogenesis are summarized in combination with a summary of the relationship between the pathogenesis of human RCC and iron metabolism. In addition to iron-mediated carcinogenesis, the ferroptosis that is triggered by the iron-dependent accumulation of lipid peroxidation and is implicated in the carcinogenesis is discussed.

Assessment of the Antitumor Activity of Green Biosynthesized Zinc Nanoparticles as Therapeutic Agent Against Renal Cancer in Rats

Zinc nanoparticles (Zn-NPs) have garnered a great deal of attention as potential cancer therapy. The use of microorganisms in the synthesis of nanoparticles emerges as an eco-friendly and exciting approach. This study was designed to assess biosynthesized Zn-NPs as therapeutic agent against kidney cancer induced by ferric-nitrilotriacetate (Fe-NTA) in rats.Zn-NPs were synthesized from edible mushroom then characterized by transmission electron microscopy analysis, dynamic light scattering, and Fourier transform infrared spectroscopy. Rats were divided into 4 different groups: group I (control), group II (Fe-NTA group), group III (Zn-NPs group), and group IV (Fe-NTA + Zn-NPs group). Animals were sacrificed then kidney and liver function tests, MDA level, glutathione, glutathione peroxidase, and superoxide dismutase activities were measured by using colorimetric methods. Caspase-3 level and carcinoembryonic antigen concentration were measured by using ELISA. Finally, DNA fragmentation was visualized by using agarose gel electrophoresis.Treatment with Zn-NPs significantly suppressed renal oxidative stress by restoring glutathione level, glutathione peroxidase, and superoxide dismutase activities and ameliorated oxidative damage parameters of lipid peroxidation as well as renal toxicity markers. Molecular and tumor markers showed significant improvement with respect to induction group, and this was well appreciated with the histopathological alteration findings in the treated groups.Microbial synthesized Zn-NPs possess antitumor-promoting activity against Fe-NTA-induced toxicity and carcinogenesis, which should be evaluated in a clinical study.

Protective effect of Boysenberry Juice on Ferric Nitrilotriacetate-induced Renal Injury in Mice

Boysenberry (Rubus loganbaccus × baileyanus Britt.) is one of the popular berries in Western countries. In the present study, the effect of the boysenberry juice on ferric nitrilotriacetate (Fe-NTA)-induced renal injury was investigated. ICR mice (7 weeks old, male) were ad libitum administered boysenberry juice for 1 week, and were intraperitoneally injected Fe-NTA (5 mg Fe/kg body weight) as an oxidant to renal. The consumption of boysenberry juice suppressed the Fe-NTA-increased thiobarbituric acid reactive substances (TBARS) in kidney and blood urea nitrogen (BUN). These results indicate that the consumption of boysenberry juice reduces the risk of oxidative stress.

Simultaneous Disinfection and Organic Microcontaminant Removal by UVC-LED-Driven Advanced Oxidation Processes

This work presents the comparison of four advanced oxidation processes driven by UVC-LED radiation (278 nm—2 W/m2) for simultaneous bacteria inactivation (Escherichia coli—106 CFU/mL) and microcontaminant removal (imidacloprid—50 µg/L) in simulated wastewater secondary effluent. To this end, the activation of H2O2 and S2O82− as precursors of HO• and SO4•−, respectively, by UVC-LED and UVC-LED/Fe3+–NTA (ferric nitrilotriacetate at 0.1 mM) has been studied at different oxidant concentrations. For the purpose of comparison, conventional chlorination was used as the baseline along with bacterial regrowth 24 h after treatment. Disinfection was achieved within the first 30 min in all of the processes, mainly due to the bactericidal effect of UVC-LED radiation. UVC-LED/H2O2 did not substantially affect imidacloprid removal due to the low HO• generation by UVC irradiation at 278 nm, while more than 80% imidacloprid removal was achieved by the UVC-LED/S2O82−, UVC-LED/Fe3+–NTA/S2O82−, and UVC-LED/Fe3+–NTA/H2O2 processes. The most efficient concentration of both oxidants for the simultaneous disinfection and microcontaminant removal was 1.47 mM. Chlorination was the most effective treatment for bacterial inactivation without imidacloprid removal. These findings are relevant for scaling up UVC-LED photoreactors for tertiary wastewater treatment aimed at removing bacteria and microcontaminants.

Contribution of temperature and photon absorption on solar photo-Fenton mediated by Fe3+-NTA for CEC removal in municipal wastewater

Solar photo-Fenton process with ferric nitrilotriacetate has great potential for contaminant of emerging concern (CEC) removal from municipal effluents. To scale-up the process, gaining know-how about the effect of temperature and photon absorption is fundamental. This work presents for the first time an in-depth study about the effect of both variables on the reaction mechanism. To this end, imidacloprid (IMD) was selected as a surrogate CEC (100 μg/L). The experimental plan comprised two steps: (i) lab-scale experiments in simulated effluents, and (ii) experiments at pilot-scale in raceway pond reactors with actual effluents. Despite the process being photo-limited in the volumetric rate of photon absorption range of 103–413 μE/m3·s, the increase in the liquid depth from 5 to 15 cm allowed improving the treatment capacity, achieving more than 80 % of IMD removal with reaction times around 30 min. These results provide the necessary knowledge for photoreactor design and continuous flow operation.

Augmented oxidative stress increases 8-oxoguanine preferentially in the transcriptionally active genomic regions

8-Oxoguanine (8-oxoG) is the most common DNA base modification in the mammalian genome, associated with oxidative stress. Here we analysed the alterations in the distribution of 8-oxoG across the entire murine genome, before and after an elevation of oxidative stress by the use of ferric nitrilotriacetate (Fe-NTA) as an oxidative stress inducer in the renal proximal tubules. We isolated DNA fragments containing 8-oxoGs with immunoprecipitation from the murine genome, and amplified them by PCR for a distribution analysis with microarray-based comparative genomic hybridisation. The distribution profiles revealed that frequencies of 8-oxoG fluctuated with a cycle of 1–10 Mb along the chromosomes and the amplitude of the fluctuation was reduced after Fe-NTA administration. The distributions of 8-oxoG along the entire genome in the control and oxidatively stressed conditions were negatively correlated with that of gene density but positively correlated with that of Lamin B1 interaction, which corresponds to lamina-associated domains. These results on the murine genome were consistent with those on the rat genome we previously reported. We further discovered a negative correlation between the distributions of 8-oxoG and transcriptional activity along the genome. Finally, a comparison of the distributions before and after Fe-NTA administration suggested that 8-oxoGs are generated in response to the augmented oxidative stress preferentially in the transcriptionally active genomic regions, where 8-oxoGs have been less accumulated in the control condition.

Differential behavior of NF-κB, IκBα and EGFR during the renal carcinogenic process in an experimental model in vivo.

Renal cell carcinoma (RCC) is the most common type of cancer of the adult kidney. It is generally asymptomatic even at advanced stages, so opportune diagnosis is rare, making it almost impossible to study this cancer at its early stages. RCC tumors induced by ferric nitrilotriacetate (FeNTA) in rats histologically correspond to the human clear cell RCC subtype (ccRCC) and the exposure to this carcinogen during either one or two months leads to different early stages of neoplastic development. High levels of nuclear factor kappa B (NF-κB) and epidermal growth factor receptor (EGFR) as well as low levels of NF-κB inhibitor alpha (IκBα) are frequent in human RCC, but their status in FeNTA-induced tumors and their evolution along renal carcinogenesis is unclear. On this basis, in the present study NF-κB, IκBα and EGFR behavior was analyzed at different stages of the experimental renal carcinogenesis model. Similar to patients with RCC, neoplastic tissue showed high levels of p65, one of the predominant subunits of NF-κB in ccRCC and of EGFR (protein and mRNA), as well as a decrease in the levels of NF-κB's main inhibitor, IκBα, resulting in a classic oncogenic combination. Conversely, different responses were observed at early stages of carcinogenesis. After one month of FeNTA-exposure, NF-κB activity and EGFR levels augmented; but unexpectedly, IκBα also did. While after two months, NF-κB activity diminished, but EGFR and IκBα levels remained elevated. In conclusion, FeNTA-induced tumors and RCC human neoplasms are analogues regarding to the classic NF-κB, IκBα and EGFR behavior, and distinctive non-conventional combination of changes is developed at each early stage studied. The results obtained suggest that the dysregulation of the analyzed molecules could be related to different signaling pathways and therefore, to particular effects depending on the phase of the carcinogenic process.

Agents-induced nephrotoxicity and catcheins

The present review was performed to gather the available literature on the nephroprotective effects of catechins against toxic agents. Several studies have demonstrated the therapeutic effects of catechins versus nephrotoxic agents such as cisplatin, cyclosporine A, tamoxifen, FK506, gentamicin, ethylene glycol, calcium, oxalate monohydrate, cadmium, ferric nitrilotriacetate, hydrogen peroxide, contrast medium, fructose, glucose, melamine vanadium, ochratoxin A, streptozotocin. However, more investigations should be done to indicate the nephroprotective effects of catechins against toxic agents in humans.

Nephroprotective effect of green tea, rosmarinic acid and rosemary on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute renal toxicity in Wistar rats.

The present study was designed to investigate the chemoprotective effect of green tea extract (GTE), rosmarinic acid (RA) and rosemary extract (RE) against diethylnitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted nephrotoxicity in rats. Forty male rats were categorized into five: Group I included healthy rats, group II received DEN+Fe-NTA, group III received 200 mg/kg b.wt. of RE+DEN+Fe-NTA, group IV received 1 g/kg b.wt. of GTE+DEN+Fe-NTA and group V received 50 mg/kg b.wt. of RA+DEN+Fe-NTA. RE, GTE, RA were given orally for 14 days before single intraperitoneal administration of DEN (160 mg/kg) till the end of the experiment. Eighteen days after DEN, a single intraperitoneal dose of Fe-NTA (5 mg Fe/kg) was administrated to rats to promote nephrotoxicity. The biochemical parameters were analyzed in serum at time intervals while the malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were assessed in both serum and renal tissues. Kidney from each group was histopathologically examined at time intervals. The administration of Fe-NTA after DEN dose to albino rats resulted in acute nephrotoxicity which was characterized by a highly significant elevation of serum urea, creatinine, uric acid (p=0.000), serum and renal MDA and TNF-α (p=0.000) with vacuolation of epithelial lining renal tubules. The administration of RE, GTE and RA prior to DEN+Fe-NTA treatment significantly ameliorated the observed increased levels of the above mentioned parameters. GTE, RA & RE exerted a protective effect against renal toxicity with GTE showing a more pronounced effect on renal function parameters while RA showed the best antioxidant impact.

Animal Models in Diabetes Mellitus: An Overview

Diabetes mellitus is defined as a state in which homeostasis of carbohydrate and lipid metabolism is improperly regulated by insulin. This results primarily in elevated fasting and postprandial blood glucose levels. If this imbalanced homeostasis dose not returns to normalcy and continues for a protracted period of time, it leads to hyperglycemia, which in due course turns into a syndrome called diabetes mellitus. Several animal models have been developed for studying diabetes mellitus or testing anti-diabetic agents. These models include chemical, surgical (pancreatectomy) and genetic manipulations in several animal species to induce diabetes mellitus. The diabetogenic drugs used include: Alloxan monohydrate, Streptozotocin with or without nicotinamide, Ferric nitrilotriacetate, Ditizona and Anti-insulin serum. The selection of these models to use for investigating the antidiabetic properties of a new compound may be a very difficult task especially for young researchers. The aim of the present review is give a brief idea about various experimental models developed for studying diabetes mellitus, assess the merits and demerits of each model and highlight the precautions needed to avoid erroneous results during the applications of these models.
 Keywords: Diabetes Mellitus, Animal models, Alloxan, Streptozotocin.

Biomolecular Interaction Studies Between Cytochrome PpcA From Geobacter sulfurreducens and the Electron Acceptor Ferric Nitrilotriacetate (Fe-NTA).

Geobacter sulfurreducens bacterium exhibits an enormous respiratory versatility, including the utilization of several toxic and radioactive metals as electron acceptors. This versatility is also replicated in the capability of the most abundant cytochrome in G. sulfurreducens, the periplasmic triheme cytochrome PpcA, to reduce uranium, chromium and other metal ions. From all possible electron transfer pathways in G. sulfurreducens, those involved in the iron reduction are the best characterized to date. Previously, we provided structural evidence for the complex interface established between PpcA and the electron acceptor Fe(III)-citrate. However, genetic studies suggested that this acceptor is mainly reduced by outer membrane cytochomes. In the present work, we used UV-visible measurements to demonstrate that PpcA is able to directly reduce the electron acceptor ferric nitrilotriacetate (Fe-NTA), a more outer membrane permeable iron chelated form. In addition, the molecular interactions between PpcA and Fe-NTA were probed by Nuclear Magnetic Resonance (NMR) spectroscopy. The NMR spectra obtained for PpcA samples in the absence and presence of Fe-NTA showed that the interaction is reversible and encompasses a positively charged surface region located in the vicinity of the heme IV. Overall, the study elucidates the formation of an electron transfer complex between PpcA and a readily outer-membrane permeable iron chelated form. The structural and functional relationships obtained explain how a single cytochrome is designed to effectively interact with a wide range of G. sulfurreducens electron acceptors, a feature that can be explored for optimal bioelectrochemical applications.

Superiority of rat over murine model for studies on the evolution of cancer genome

Evolution of the species and carcinogenesis are similar in that genomic alterations are the key events. Oxidative stress derived from various etiologies is one of the major causes of carcinogenesis by inducing mutations in the genome. Persistent oxidative stress in the renal proximal tubules through Fenton reaction catalysed by ferric nitrilotriacetate (Fe-NTA) generates renal cell carcinoma (RCC) in mice and rats. Here, in order to observe the species difference in oxidative stress-induced carcinogenesis and to obtain an insight regarding the characteristics of each species, we compared the genomic alterations using array-based comparative genome hybridisation among RCCs in Mutyh knockout/wild-type mice (C57BL/6 background) induced by Fe-NTA, RCCs in F1 hybrids of Brown-Norway/Fischer-344 wild-type rats and clear cell renal cell carcinoma (CCRCC)/papillary renal cell carcinoma (PRCC) of humans. The average deviated fraction of genomic segments, either loss or gain, from the standard biallelic position was 0.220 (N = 4), 0.304 (N = 11), 0.283 (N = 12), and 0.261 (N = 5), respectively, for murine RCC, rat RCC, human CCRCC, and human PRCC. Notably, gain/loss ratio was remarkably different as indicated by 0.0820, 0.161, 0.821, and 4.44, respectively. These data suggest that higher species require more genomic alterations with amplification preference for renal carcinogenesis. Further studies are necessary to identify the molecular mechanisms whether the present results depend on cellular functional differences, etiology of carcinogenesis or the target cells in carcinogenesis.