Hazardous impact of diclofenac on mammalian system: Mitigation strategy through green remediation approach.

Diclofenac is an anti-inflammatory drug used as an analgesic. It is often detected in various environmental sources around the world and is considered as one of the emerging contaminants (ECs). This paper reviews the distribution of diclofenac at high concentrations in diverse environments and its adverse ecological impact. Recent studies observed strong evidence of the hazardous effect of diclofenac on mammals, including humans. Diclofenac could cause gastrointestinal complications, neurotoxicity, cardiotoxicity, hepatotoxicity, nephrotoxicity, hematotoxicity, genotoxicity, teratogenicity, bone fractures, and skin allergy in mammals even at a low concentration. Collectively, this comprehensive review relates the mode of toxicity, level of exposure, and route of administration as a unique approach for addressing the destructive consequence of diclofenac in mammalian systems. Finally, the mitigation strategy to eradicate the diclofenac toxicity through green remediation is critically discussed. This review will undoubtedly shed light on the toxic effects of pseudo-persistent diclofenac on mammals as well as frame stringent guidelines against its common usage.

Novel antioxidant astaxanthin-s-allyl cysteine biconjugate diminished oxidative stress and mitochondrial dysfunction to triumph diabetes in rat model.

AIMS: The present study determines the effect of administration of novel antioxidant astaxanthin-s-allyl cysteine biconjugate (AST-SAC) against streptozotocin-induced diabetes mellitus (DM) in rats. MAIN METHODS: AST-SAC (1 mg/kg/day) was treated against DM in rats for 45 days. The oxidative stress, antioxidants level, insulin secretion, activities of various carbohydrate metabolizing enzymes were studied. The glucose uptake in L6 myotubes was studied. In addition, in silico analysis of interaction of AST-SAC with proteins such as insulin receptor (IR) and 5'-adenosine monophosphate-activated protein kinase (AMPK) were carried out. KEY FINDINGS: Administration of AST-SAC in DM rats has protected the mitochondrial function (decreased oxidative stress and normalized oxidative phosphorylation activities) and antioxidant capacity of the pancreas which has resulted in beta cells rejuvenation and insulin secretion restoration. AST-SAC decreased the alpha-glucosidases activities to bring glycemic control in DM rats. Due to these effects the glycoprotein components and lipids were restored to near normalcy in DM rats. AST-SAC protected the antioxidant status of liver, kidney and plasma; and curbed the progression of secondary complications of DM. AST-SAC treatment stimulated glucose uptake in L6 myotubes in in vitro. To support this observation, AST-SAC interacted with proteins such as IR and AMPK in silico. SIGNIFICANCE: AST-SAC can be considered as "multi-target-directed ligand", that is, through these manifold effects, AST-SAC has been able to prevail over DM in rats.

Occurrence, interactive effects and ecological risk of diclofenac in environmental compartments and biota - a review.

Diclofenac, a nonsteroidal anti-inflammatory drug has turned into a contaminant of emerging concern; hence, it was included in the previous Watch List of the EU Water Framework Directive. This review paper aims to highlight the metabolism of diclofenac at different trophic levels, its occurrence, ecological risks, and interactive effects in the water cycle and biota over the past two decades. Increased exposure to diclofenac not only raises health concerns for vultures, aquatic organisms, and higher plants but also causes serious threats to mammals. The ubiquitous nature of diclofenac in surface water (river, lake canal, estuary, and sea) is compared with drinking water, groundwater, and wastewater effluent in the environment. This comprehensive survey from previous studies suggests the fate of diclofenac in wastewater treatment plants (WWTPs) and may predict its persistence in the environment. This review offers evidence of fragmentary available data for the water environment, soil, sediment, and biota worldwide and supports the need for further data to address the risks associated with the presence of diclofenac in the environment. Finally, we suggest that the presence of diclofenac and its metabolites in the environment may represent a high risk because of their synergistic interactions with existing contaminants, leading to the development of drug-resistant strains and the formation of newly emerging pollutants.

Plant extract as environmental-friendly green catalyst for the reduction of hexavalent chromium in tannery effluent.

The aqueous extract of various plants like Coriandrum sativum (AECS), Alternanthera tenella colla (AEAT), Spermacoce hispida (AESH) and Mollugo verticillata (AEMV) was studied for its hexavalent chromium (CrVI) reduction property. Even though antioxidant activity was present, AEAT, AESH and AEMV did not reduce CrVI. AECS showed rapid and dose-dependent CrVI reduction. The efficient reduction of 50 mg/L of CrVI using AECS was attained in the presence of 250 µg/mL of starting plant material, incubating the reaction mixture at pH 2, 30°C and agitation at 190 rpm. Under such conditions, about 40 mg/L of CrVI was reduced at 3 h of incubation. FT-IR analysis revealed the involvement of phenols, alcohols, alpha-hydroxy acid and flavonoids present in the AECS for the CrVI reduction. These results indicate that not all the plant extracts with rich antioxidants are capable of reducing CrVI. Using the conditions standardized in the present study, AECS reduced about 80% of CrVI present in the tannery effluent. These results signify the application of AECS as an eco-friendly method in the wastewater treatment.

Rapid biosynthesis of Bauhinia variegata flower extract-mediated silver nanoparticles: an effective antioxidant scavenger and α-amylase inhibitor.

Silver nanoparticles (AgNPs) were biosynthesized using Bauhinia variegata flower extract (BVFE). The BVF-AgNPs was found to be spherical shaped with the size of 5-15 nm. The phytoconstituents analysis and FTIR spectrum indicated that bioactive compounds like, phenols, flavonoids, benzophenones, nitro compounds, aromatics and aliphatic amines from BVFE might absorb on the surface of BVF-AgNPs. The synthesized BVF-AgNPs showed potent antioxidant property and α-amylase enzyme activity inhibition. The IC50 value of BVF-AgNPs was found to be 4.64 and 16.6 µg/ml for DPPH and ferric reducing power assay, respectively. The IC50 value of BVF-AgNPs for α-amylase inhibition was found to be 38 µg/ml. The Ki value of BVF-AgNPs for α-amylase inhibitory effect was found to be 21 µg/ml with the non-competitive mode of inhibition. These results suggest that BVF-AgNPs might be an effective nano-drug to treat diabetic conditions.

Alteration of paraoxonase, arylesterase and lactonase activities in people around fluoride endemic area of Tamil Nadu, India.

BACKGROUND: Toxicity due to excess fluoride concentration in drinking water is of great concern in people who rely only on the ground water as their water source in many region of the world. METHODS: We collected samples and examined the toxicity of fluoride in a population residing at Salem, Dharmapuri and Krishnagiri districts of Tamil Nadu, India and measured HDL bound enzyme (PON1), erythrocyte membrane bound enzymes (acetylcholinesterase, AChE) and adenosine 5' triphosphatase (ATPases), plasma enzyme (butyrylcholinesterase, BChE) and rate limiting enzyme in heme biosynthesis (delta aminolevulinic acid dehydratase, δ-ALAD) activities. RESULTS: In fluorosis patients, formation of lipid peroxidation product was more in erythrocytes than in plasma. The observation further revealed that there was 50% reduction in the activity of HDL bound anti atherogenic enzyme-paraoxonase (PON1). The activities of membrane bound and signaling enzymes (acetylcholinesterase - AChE and adenosine 5' triphosphatase - ATPase) of erythrocyte were also diminished. These results suggested that there was defectiveness in the signaling and energy metabolism in fluorosis patients. Altered isoenzyme pattern of lactate dehydrogenase (LDH) in fluorosis samples was observed. Furthermore, the result suggested that both the heart (LDH 1) and liver (LDH 5) were most affected by fluoride toxicity. The study also provided reference values for tests which are used to predict the severity of fluoride toxicity. CONCLUSION: The toxic effect of fluoride was due to the collective effects on vital protective system rather than single factor.

New amino acid-Schiff base derived from s-allyl cysteine and methionine alleviates carbon tetrachloride-induced liver dysfunction.

In spite of the tremendous stride in modern medicine, conventional drugs used in the hepatotoxic management are mostly inadequate. The present study aims in the synthesis of novel Schiff base compound derived using s-allyl cystiene and methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1-carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was characterized using UV-visible spectrophotometer, FTIR, 1HNMR, and GC-MS. ACEMB showed potent in vitro antioxidant property. Chronic administration of ACEMB prior to CCl4 intoxication: i) attenuated the leakage of liver injury markers, such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into the blood circulation; ii) normalized the concentration of total proteins, albumin and globulin to control level; and iii) protected the liver against dyslipidemia. These effects of ACEMB show the preservation of endoplasmic reticulum function against CCl4 toxicity in the liver. The protective effect of ACEMB was due to its antioxidant property, which was revealed by reduced oxidative stress (TBARS and HP) and enhanced functions of the endogenous antioxidative system (SOD, catalase, GPx, GST, GSH, vitamin E and C) against CCl4 intoxication. Also, ACEMB protected the functional activities of the various mitochondrial tricarboxylic acid cycle and oxidative phosphorylation enzymes. The biochemical alterations are in concurrence with the histological observations, wherein ACEMB pretreatment prevented the vacuolation, degeneration of nuclei and necrosis of hepatocytes. In addition, in silico analysis reveals the interaction of ACEMB in the active site of cytochrome P450. ACEMB mediates hepatoprotective effect by substituting itself as an antioxidant and decreasing oxidative stress, thereby diminishing the intracellular organelle dysfunction against CCl4 toxicity in the liver.

Anti-acne, anti-dandruff and anti-breast cancer efficacy of green synthesised silver nanoparticles using Coriandrum sativum leaf extract.

In this present investigation, AgNPs were green synthesised using Coriandrum sativum leaf extract. The physicochemical properties of AgNPs were characterised using UV-visible spectrophotometer, field emission scanning microscopy/energy dispersive X-ray (FESEM/EDX), Fourier transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET) analysis. Further, in vitro anti-acne, anti-dandruff and anti-breast cancer efficacy of green synthesised AgNPs were assessed against Propionibacterium acnes MTCC 1951, Malassezia furfur MTCC 1374 and human breast adenocarcinoma (MCF-7) cell line, respectively. The flavonoids present in the plant extract were responsible for the AgNPs synthesis. The green synthesised nanoparticles size was found to be ≈37nm. The BET analysis result shows that the surface area of the synthesised AgNPs was found to be 33.72m(2)g(-1). The minimal inhibitory concentration (MIC) of AgNPs for acne causative agent P. acnes and dandruff causative agent M. furfur was found to be at 3.1 and 25µgmL(-1), respectively. The half maximal inhibitory concentration (IC50) value of the AgNPs for MCF-7 cells was calculated as 30.5µgmL(-1) and complete inhibition was observed at a concentration of 100µgmL(-1). Finally, our results proved that green synthesised AgNPs using C. sativum have great potential in biomedical applications such as anti-acne, anti-dandruff and anti-breast cancer treatment.

Phyto-synthesis of silver nanoparticles using Alternanthera tenella leaf extract: an effective inhibitor for the migration of human breast adenocarcinoma (MCF-7) cells.

In this study, phyto-synthesis of silver nanoparticles (AgNPs) was achieved using an aqueous leaf extract of Alternanthera tenella. The phytochemical screening results revealed that flavonoids are responsible for the AgNPs formation. The AgNPs were characterised using UV-visible spectrophotometer, field emission scanning microscopy/energy dispersive X-ray, transmission electron microscopy, fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction. The average size of the nanoparticles was found to be ≈48 nm. The EDX results show that strong signals were observed for the silver atoms. The strong band appearing at 1601-1595 cm(-1) correspond to C-C stretching vibration from dienes in FT-IR spectrum indicating the formation of AgNPs. Human breast adenocarcinoma (MCF-7) cells treated with various concentrations of AgNPs showed a dose-dependent increase in cell inhibition. The IC50 value of the AgNPs was calculated to be 42.5 µg mL(-1). The AgNPs showed a significant reduction in the migration of MCF-7 cells.

Osteonecrosis with renal damage in HIV patients undergoing HAART.

Rheumatoid arthritis in HIV patients undergoing HAART is associated with increased risk of side effect. Elevation of uric acid (UA) is important in tissue damage, deposition of crystal in joints leads to the development of rheumatoid arthritis in the HAART complaint group. This study was carried out to investigate the relationship of uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group. Moreover; the ratio of uric acid/cystatin C, uric acid/urea and uric acid/creatinine were also studied. To analyze the progression of HIV, the immunological parameters were correlated with uric acid. Our result showed a statistically high significant increase in uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group when compared to HAART non-complaint group, early stage and control. The ratio of uric acid/cystatin C, uric acid/urea, uric acid/creatinine were significantly increased in the HAART complaint group. Statistically significant positive correlation was observed between uric acid and cystatin C, urea, creatinine, absolute CD4 and CD8 count. The increased level of uric acid, RA factor, ANA, ESR, cystatin C and increased ratio of uric acid/cystatin C in the HAART complaint group might conclude the mechanism underlying the increased risk for rheumatoid arthritis in the HAART complaint group which may relate to the combined effects of low-grade inflammation and renal dysfunction.

Manganese peroxidase h4 isozyme mediated degradation and detoxification of triarylmethane dye malachite green: optimization of decolorization by response surface methodology.

A cDNA encoding for manganese peroxidase isozyme H4 (MnPH4), isolated from Phanerochaete chrysosporium, was expressed in Pichia pastoris, under the control of alcohol oxidase I promoter. The recombinant MnPH4 was efficiently secreted onto media supplemented with hemin at a maximum concentration of 500 U/L, after which purified rMnPH4 was used to decolorize the triarylmethane dye malachite green (MG). Response surface methodology (RSM) was employed to optimize three different operational parameters for the decolorization of MG. RSM showed that the optimized variables of enzyme (0.662 U), MnSO4 (448 µM), and hydrogen peroxide (159 µM) decolorized 100 mg/L of MG completely at 3 h. Additionally, UV-VIS spectra, high-performance liquid chromatography, gas chromatography-mass spectrometry, and liquid chromatography-electrospray ionization/mass spectrometry analysis confirmed the degradation of MG by the formation of main metabolites 4-dimethylamino-benzophenone hydrate, N, N-dimethylaniline (N,N-dimethyl-benzenamine), and methylbenzaldehyde. Interestingly, it was found that rMnPH4 mediates hydroxyl radical attack on the central carbon of MG. Finally, rMnPH4 degraded MG resulted in the complete removal of its toxicity, which was checked under in vitro conditions.

Detoxification of malachite green by Pleurotus florida laccase produced under solid-state fermentation using agricultural residues.

Laccase was produced from Pleurotus florida under solid-state fermentation, and the production was optimized by response surface methodology. The predicted maximum laccase production of 8.81 U g(-1) was obtained by the optimum concentration of malt extract, banana peel, wheat bran and CuSO4, which was found to be 0.69 g, 10.61 g, 10.68 g and 77.15 ppm, respectively. The validation results suggested that the laccase production was 7.96 U g(-1) in the optimized medium, which was close to the predicted value. Decolorization efficiency of P. florida laccase was evaluated against malachite green (MG). Rapid decolorization of MG dye was observed, and a dark-coloured precipitate was formed in the reaction mixture. HPLC analysis indicated that the laccase enzyme degraded MG by the demethylation process. The toxicity of MG was reduced to 67% after the treatment with laccase, which was confirmed by a phytotoxicity study.

Laccase-poly(lactic-co-glycolic acid) (PLGA) nanofiber: highly stable, reusable, and efficacious for the transformation of diclofenac.

Nanobiocatalysis has received growing attention for use in commercial applications. We investigated the efficiency, stability, and reusability of laccase-poly(lactic-co-glycolic acid) (PLGA) nanofiber for diclofenac transformation. NH stretching vibrations (3400-3500 cm(-1) and 1560 cm(-1)) in FT-IR spectra confirmed immobilization of laccase on PLGA nanofibers. The relative activity of immobilized laccase was 82% that of free laccase. Immobilized laccase had better storage, pH, and thermal stability than free laccase. The immobilized laccase produced complete diclofenac transformation in three reuse cycles, which was extended to 6 cycles in the presence of syringaldehyde. Results suggest that laccase-PLGA nanofiber may be useful for removing diclofenac from aqueous sources and has potential for other commercial applications.

Beta-2 microglobulin as an immunological marker to assess the progression of human immunodeficiency virus infected patients on highly active antiretroviral therapy.

BACKGROUND: Acquired immune deficiency syndrome (AIDS) defines the end stage of Human immunodeficiency viral (HIV) infection before the introduction of highly active antiretroviral therapy (HAART). This study was carried out to assess the serum ß-2 microglobulin (B2M) as a marker for progression of HIV infected patients undergoing HAART. METHODS: Blood samples were collected from 50 subjects of HIV infected patients residing at semi urban area undergoing treatment at Chellam Hospital, Salem, India. Twenty five age-matched healthy subjects were taken as control group. Serum B2M level was measured by using enzyme immunoassay, absolute CD4 and CD8 counts were carried out by single platform (SP) technology using a flow cytometer. Viral RNA was measured by real time PCR. The serum LDH level and total WBC count were also measured. RESULTS: Our result showed a statistically high significant increase in B2M in HIV patients on HAART non complaint group whereas absolute CD4, CD8 count, CD4/CD8 ratio and WBC count were decreased significantly when compared to control and HAART complaint group. Statistically a significant negative correlation was observed between B2M and absolute CD4, CD8 count, CD4/CD8 ratio and WBC count. B2M showed a significantly positive correlation with viral RNA and LDH values. CONCLUSIONS: The increase of B2M and reduced absolute CD4, CD8 count, CD4/CD8 ratio and WBC count in HIV patients on HAART non complaint group may have a contributory role in the immune progression of HIV with interruption of HAART. B2M plays an important role in the diagnosis of HIV and might indicate HIV progression.

Optimization of laccase production by Pleurotus ostreatus IMI 395545 using the Taguchi DOE methodology.

Production of laccase using a submerged culture of Pleurotus orstreatus IMI 395545 was optimized by the Taguchi orthogonal array (OA) design of experiments (DOE) methodology. This approach facilitates the study of the interactions of a large number of variables spanned by factors and their settings, with a small number of experiments, leading to considerable savings in time and cost for process optimization. This methodology optimizes the number of impact factors and enables to calculate their interaction in the production of industrial enzymes. Eight factors, viz. glucose, yeast extract, malt extract, inoculum, mineral solution, inducer (1 mM CuSO4) and amino acid (l-asparagine) at three levels and pH at two levels, with an OA layout of L18 (2¹ × 37) were selected for the proposed experimental design. The laccase yield obtained from the 18 sets of fermentation experiments performed with the selected factors and levels was further processed with Qualitek-4 software. The optimized conditions shared an enhanced laccase expression of 86.8% (from 485.0 to 906.3 U). The combination of factors was further validated for laccase production and reactive blue 221 decolorization. The results revealed an enhanced laccase yield of 32.6% and dye decolorization up to 84.6%. This methodology allows the complete evaluation of main and interaction factors.

Environmentally stable adsorbent of tetrahedral silica and non-tetrahedral alumina for removal and recovery of malachite green dye from aqueous solution.

The conventional adsorbents like activated carbon, agricultural wastes, molecular sieves, etc., used for dye adsorption are unstable in the environment for long time, and hence the adsorbed dyes again gets liberated and pollute the environment. To avoid this problem, environmentally stable adsorbent of silica and alumina should be employed for malachite green adsorption. The adsorbents were characterized by Fourier transformed infrared spectroscopy (FT-IR) to confirm the tetrahedral framework of silica and non-tetrahedral framework of alumina. The adsorption equilibrium of dye on alumina and silica were 4 and 5h, respectively, this less adsorption time on alumina might be due to the less activation energy on alumina (63.46 kJ mol(-1)) than silica (69.93 kJ mol(-1)). Adsorption increased with increase of temperature on silica, in alumina, adsorption increased up to 60 degrees C, and further increase of temperature decreased the adsorption due to the structural change of non-tetrahedral alumina in water. The optimum pH for dye adsorption on alumina was 5 and silica was 6. The dye adsorptions on both adsorbents followed pseudo-second-order kinetics. The adsorption well matched with Langmuir and Freundlich adsorption isotherms and found that adsorption capacity on alumina was more than silica. The thermodynamic studies proved that the adsorption was endothermic and chemisorptions (DeltaH degrees >40 kJ mol(-1)) on alumina and silica. Recovery of dye on alumina and silica were studied from 30 to 90 degrees C and observed that 52% of dye was recovered from alumina and only 3.5% from silica. The less recovery on silica proved the strong adsorption of dye on silica than alumina.