An In Vitro and In Vivo Study of the Efficacy and Toxicity of Plant-Extract-Derived Silver Nanoparticles.

Silver nanoparticles (AgNPs) display unique plasmonic and antimicrobial properties, enabling them to be helpful in various industrial and consumer products. However, previous studies showed that the commercially acquired silver nanoparticles exhibit toxicity even in small doses. Hence, it was imperative to determine suitable synthesis techniques that are the most economical and least toxic to the environment and biological entities. Silver nanoparticles were synthesized using plant extracts and their physico-chemical properties were studied. A time-dependent in vitro study using HEK-293 cells and a dose-dependent in vivo study using a Drosophila model helped us to determine the correct synthesis routes. Through biological analyses, we found that silver nanoparticles' cytotoxicity and wound-healing capacity depended on size, shape, and colloidal stability. Interestingly, we observed that out of all the synthesized AgNPs, the ones derived from the turmeric extract displayed excellent wound-healing capacity in the in vitro study. Furthermore, the same NPs exhibited the least toxic effects in an in vivo study of ingestion of these NPs enriched food in Drosophila, which showed no climbing disability in flies, even at a very high dose (250 mg/L) for 10 days. We propose that stabilizing agents played a superior role in establishing the bio-interaction of nanoparticles. Our study reported here verified that turmeric-extract-derived AgNPs displayed biocompatibility while exhibiting the least cytotoxicity.

Combating silver nanoparticle-mediated toxicity in Drosophila melanogaster with curcumin.

Nanoscale materials display unique physical and chemical properties that enable their assimilation into a variety of industrial and consumer products. Amongst the widely used nanomaterials, silver nanoparticles (AgNPs) have gained tremendous recognition for various applications, owing to their extraordinary plasmonic and bactericidal properties. Despite of the extensive usage of AgNPs in various sectors, its impact on human health remains ambiguous. Several studies have established that higher doses of AgNPs are detrimental to organismal health. In order to attain the best from these versatile nanoparticles, a recent advent of green nanotechnology, that is, employment of metal nanoparticles synthesized using plant extracts, has emerged. Here, using Drosophila as a model system, we tested if adding curcumin, a biologically active polyphenolic compound present in turmeric, having multitudes of therapeutic properties, could mitigate AgNP-mediated biotoxicity. We found that co-administration of AgNPs with curcumin in the fly food could alleviate several harmful effects evoked by AgNPs ingestion in Drosophila model. Addition of curcumin superseded reduction in feeding, pupation, eclosion, pigmentation, and fertility caused by AgNPs ingestion. Interestingly, impairment in ovary development observed in flies reared on AgNPs-supplemented food was also partially restored by co-administration of AgNPs with curcumin. Furthermore, substantial alleviation of reactive oxygen species level and cell death was observed in larval tissues upon co-supplementation of AgNPs with curcumin. We therefore propose that curcumin, when administered with AgNPs, can abrogate the toxic manifestations of AgNPs ingestion and hence can be incorporated in various consumer products encompassing it.

Discriminatory alteration of carbohydrate homeostasis by gold nanoparticles ingestion in Drosophila.

With the extensive usage of gold nanoparticles (AuNPs) in various industrial sectors and biomedical applications, evaluation of their possible effects on human health becomes imperative. Therefore, the present study was aimed toward assessing the dose-dependent impact of AuNPs ingestion on metabolic homeostasis using Drosophila melanogaster as a model system. We found that larval ingestion of higher dose of AuNPs significantly reduced body weight. Further analysis of the crucial energy reservoir showed selective alteration in carbohydrate levels without any change in the lipid and protein levels. Transcriptional downregulation of glycogen synthase further supported impaired glycogen metabolism in flies supplemented with higher dose of AuNPs. Additionally, ingestion of higher dose of AuNPs in larvae results in significantly increased levels of reactive oxygen species (ROS) in the peripheral tissues, suggestive of stress condition. Our findings clearly imply that supplementing higher doses of AuNPs at an early developmental stage can potentially cause weight loss, impair glycogen metabolism, and elevate ROS production. Therefore, determination of a biologically effective dose is critical for the safety of mankind and vulnerable populations at the workplace.

Sedentary behavior and altered metabolic activity by AgNPs ingestion in Drosophila melanogaster.

Among several nanoparticles, silver nanoparticles (AgNPs) are extensively used in a wide variety of consumer products due to its unique antimicrobial property. However, dosage effect of AgNPs on behavior and metabolic activity in an in vivo condition is not well studied. Therefore, to elucidate the impact of AgNPs on behavior and metabolism, systematic and detailed dosages study of AgNPs was performed by rearing Drosophila melanogaster on food without and with AgNPs. We found that dietary intake of AgNPs at early larval stage leads to behavioral abnormalities such as poor crawling and climbing ability of larvae and adults respectively. Interestingly, intake of higher dosage of AgNPs at larval stage significantly altered metabolic activity that includes lipid, carbohydrate and protein levels in adult flies. Further, detailed analysis revealed that AgNPs causes remarkable reduction in the number of lipid droplets (LDs) which are lipid storage organelles in Drosophila. We also observed an increased production of reactive oxygen species (ROS) in AgNPs ingested larval tissues. These results strongly imply that higher dosage of AgNPs ingestion from early larval stage of Drosophila is inimical and thereby draws concern towards the usage of AgNPs in consumer goods.

Dose-dependent effect of silver nanoparticles (AgNPs) on fertility and survival of Drosophila: An in-vivo study.

Silver nanoparticles (AgNPs) containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs.

Unusual presentation of an uncommon abdominal pathology.

Desmoid tumour is a non-encapsulated locally invasive tumour, originating from fibroblasts, which has ubiquitous distribution in the body. It has a high tendency for local recurrence, causing deformity in the adjacent organ and consequent organ dysfunction. A case of a 75-year-old man, presenting with high-grade fever, dull aching abdominal pain and weight loss, suspected to be due to malignancy, is reported. Contrast-enhanced computed tomography (CECT) showed a mass in the transverse colon with pericolic collection raising a suspicion of perforation. He underwent a two-stage procedure in the form of defunctioning ileostomy in the initial setting followed by colonic resection and anastomosis 6 weeks later. Histological analysis revealed mesenteric fibromatosis (desmoid tumour). The patient was completely asymptomatic one year after surgery. We report this case, as our patient had none of the predisposing factors. To the best of our knowledge, this is the first case on colonic perforation secondary to desmoid tumour.

Factors influencing mortality in acute pancreatitis: can we alter them?

Severe acture pancreatitis (SAP), a multisystem disease, is characterized by multiple organ system failure and additionally by local pancreatic complications such as necrosis, abscess, or pseudocyst. The rate of mortality in SAP, which is about 20% of all cases of acute pancreatitis (AP), may be as high as 25%, as in infected pancreatic necrosis. The factors that influence mortality in different degrees are various. Etiology for the episode, age, sex, race, ethnicity, genetic makeup, severity on admission, and the extent and nature of pancreatic necrosis (sterile vs. infected) influence the mortality. Other factors include treatment modalities such as administration of prophylactic antibiotics, the mode of feeding (TPN vs. enteral), ERCP with sphincterotomy, and surgery in selected cases. Epidemiological studies indicate that the incidence of AP is increasing along with an increase in obesity, a bad prognostic factor. Many studies have indicated a worse prognosis in idiopathic AP compared to pancreatitis induced by alcoholism or biliary stone. The risk for SAP after ERCP is the subject of extensive study. AP after trauma, organ transplant, or coronary artery bypass surgery is rare but may be serious. Since Ranson reported early prognostic criteria, a number of attempts have been made to simplify or add new clinical or laboratory studies in the early assessment of severity. Obesity, hemoconcentration on admission, presence of pleural effusion, increased fasting blood sugar, as well as creatinine, elevated CRP in serum, and urinary trypsinogen levels are some of the well-documented factors in the literature. The role of appropriate prophylactic antibiotic therapy although still is highly controversial, in properly chosen cases appears to be beneficial and well accepted in clinical practice. Early enteral nutrition has gained much support and jejunal feeding bypassing the pancreatic stimulatory effect of it in the duodenum is desirable in selected cases. The limited role for endoscopic sphincterotomy in patients with demonstrated dilated CBD with impacted stone and evidence of impending cholangitis is well documented. Surgery in AP other than for removal of the gallbladder is often limited to infected pancreatic necrosis, pseudocysts, and pancreatic abscess and in some cases of traumatic pancreatitis with a ruptured duct system. The progress in the understanding of the role of cytokines will over us opportunities to use immunomodulatory therapies to improve the outcome in SAP.