There are various substances that can disrupt the homeostatic mechanisms of the body, defined as endocrine-disrupting chemicals (EDCs). The persistent nature of microplastics (MPs) is a cause for ...concern due to their ability to accumulate in food chains and widespread use, making their toxic effects particularly alarming. The potential of MPs for disrupting the endocrine system was observed in multiple tissues. Moreover, the adrenal gland is known to be extremely sensitive to EDCs, while with the effect of MPs on the adrenal gland has not previously been studied. This study aimed to highlight the potential polyethylene microplastics (PE-MPs) induced adreno-toxic effects rather than exploring the implicated mechanisms and concluding if melatonin (Mel) can afford protection against PE-MPs induced adreno-toxicity. To fulfill the goal, six groups of rats were used; control, Mel, PE-MPs (3.75 mg/kg), PE-MPs (15 mg/kg), PE-MPs (3.75 mg/kg) +Mel, and PE-MPs (15 mg/kg) +Mel. PE-MPs induced toxic changes in the adrenal cortex, which was evident by increased adrenal weight, histopathological examination, and ultrastructural changes detected by electron microscope. A reduction in serum cortisol and an increase in serum adrenocorticotropic hormone resulted from the adreno-toxic effects of PE-MPs. Mechanisms may include the reduction of steroidogenesis-related genes, as PE-MPs drastically reduce mRNA levels of StAR, Nr0b1, Cyp11A1, as well as Cyp11B1. Also, oxidative stress that results from PE-MPs is associated with higher rates of lipid peroxidation and decreased superoxide dismutase and glutathione. PE-MPs inflammatory effect was illustrated by elevated expression of IL-1β and NF-ķB, detected by immunohistochemical staining, in addition to increased expression of caspase-3 and mRNA of Bax, markers of proapoptotic activity. The impacts of PE-MPs were relatively dose-related, with the higher dose showing more significant toxicity than the lower one. Mel treatment was associated with a substantial amelioration of PE-MPs-induced toxic changes. Collectively, this study fills the knowledge gap about the MPs-induced adrenal cortex and elucidates various related toxic mechanisms. It also supports Mel’s potential protective activity through antioxidant, anti-inflammatory, anti-apoptotic, and gene transcription regulatory effects.
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•The first study reports polyethylene microplastics-induced adrenal toxicity in rats.•A reduction in serum cortisol and an increase in serum ACTH resulted from adreno-toxic effects of (PE)-MPs.•PE-MPs inflammatory effect was illustrated by elevated expression of IL-1β and NF-ķB.•Melatonin treatment was associated with a substantial amelioration of PE-MPs-induced toxic changes.
There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is ...a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0–6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1β and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1β concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP’s toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin.
Treatment-resistant depression in later life El Bayoumi, Heba, BSc (pharm); Ismail, Zahinoor, MD
Journal of psychiatry & neuroscience,
11/2015, Volume:
40, Issue:
6
Journal Article
Peer reviewed
Open access
A 66-year-old woman was referred for management of treatment-resistant depression (TRD). She had previously undergone a 12-week trial of sertraline up to 150 mg and then another 12- week trial of ...venlafaxine up to 225 mg. She initially presented with low mood and anhedonia and no longer enjoyed spending time with her grandson. Depression is common in elderly patients, with a prevalence of up to 42.0% in adults aged 65 years or older. While there is no consensus definition of TRD, the one most commonly used is therapeutic failure following trials of 2 or more antidepressants at adequate doses and duration. Thus, a high index of suspicion is recommended for identifying pharmacokinetic drug interactions, particularly in elderly patients. Finally, depression and cognition are intimately connected in older adults with late-onset depressive episodes, increasing the risk for dementia. In this case, cognition should be monitored over time with a low threshold for workup of neurodegenerative/vascular disease.
Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could ...accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg/kg), TG14 (tigecycline, 14 mg/kg), GM (gentamicin, 80 mg/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity.
Cadmium (Cd) is a hazardous environmental pollutant that menaces human and animal health and induces serious adverse effects in various organs, particularly the liver and kidneys. Thus, the current ...study was designed to look into the possible mechanisms behind the ameliorative activities of
Tamarindus indica
(TM) and coenzyme Q10 (CoQ) combined therapy toward Cd-inflicted tissue injury. Male Wistar rats were categorized into seven groups: Control (received saline only); TM (50 mg/kg); CoQ (40 mg/kg); Cd (2 mg/kg); (Cd + TM); (Cd + CoQ); and (Cd + TM + CoQ). All the treatments were employed once daily
via
oral gavage for 28 consecutive days. The results revealed that Cd exposure considerably induced liver and kidney damage, evidenced by enhancement of liver and kidney function tests. In addition, Cd intoxication could provoke oxidative stress evidenced by markedly decreased glutathione (GSH) content and catalase (CAT) activity alongside a substantial increase in malondialdehyde (MDA) concentrations in the hepatic and renal tissues. Besides, disrupted protein and lipid metabolism were noticed. Unambiguously, TM or CoQ supplementation alleviated Cd-induced hepatorenal damage, which is most likely attributed to their antioxidant and anti-inflammatory contents. Interestingly, when TM and CoQ were given in combination, a better restoration of Cd-induced liver and kidney damage was noticed than was during their individual treatments.
Amoxicillin/clavulanate (Co-Amox), a commonly used antibiotic for the treatment of bacterial infections, has been associated with drug-induced liver damage. Quercetin (QR), a naturally occurring ...flavonoid with pleiotropic biological activities, has poor water solubility and low bioavailability. The objective of this work was to produce a more bioavailable formulation of QR (liposomes) and to determine the effect of its intraperitoneal pretreatment on the amelioration of Co-Amox-induced liver damage in male rats. Four groups of rats were defined: control, QR liposomes (QR-lipo), Co-Amox, and Co-Amox and QR-lipo. Liver injury severity in rats was evaluated for all groups through measurement of serum liver enzymes, liver antioxidant status, proinflammatory mediators, and microbiota modulation. The results revealed that QR-lipo reduced the severity of Co-Amox-induced hepatic damage in rats, as indicated by a reduction in serum liver enzymes and total liver antioxidant capacity. In addition, QR-lipo upregulated antioxidant transcription factors SIRT1 and Nrf2 and downregulated liver proinflammatory signatures, including IL-6, IL-1β, TNF-α, NF-κB, and iNOS, with upregulation in the anti-inflammatory one, IL10. QR-lipo also prevented Co-Amox-induced gut dysbiosis by favoring the colonization of Lactobacillus, Bifidobacterium, and Bacteroides over Clostridium and Enterobacteriaceae. These results suggested that QR-lipo ameliorates Co-Amox-induced liver damage by targeting SIRT1/Nrf2/NF-κB and modulating the microbiota.
Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the ...pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.
Human health and its improvement are the main target of several studies related to medical, agricultural and industrial sciences. The human health is the primary conclusion of many studies. The ...improving of human health may include supplying the people with enough and safe nutrients against malnutrition to fight against multiple diseases like COVID-19. Biofortification is a process by which the edible plants can be enriched with essential nutrients for human health against malnutrition. After the great success of biofortification approach in the human struggle against malnutrition, a new biotechnological tool in enriching the crops with essential nutrients in the form of nanoparticles to supplement human diet with balanced diet is called nano-biofortification. Nano biofortification can be achieved by applying the nano particles of essential nutrients (e.g., Cu, Fe, Se and Zn) foliar or their nano-fertilizers in soils or waters. Not all essential nutrients for human nutrition can be biofortified in the nano-form using all edible plants but there are several obstacles prevent this approach. These stumbling blocks are increased due to COVID-19 and its problems including the global trade, global breakdown between countries, and global crisis of food production. The main target of this review was to evaluate the nano-biofortification process and its using against malnutrition as a new approach in the era of COVID-19. This review also opens many questions, which are needed to be answered like is nano-biofortification a promising solution against malnutrition? Is COVID-19 will increase the global crisis of malnutrition? What is the best method of applied nano-nutrients to achieve nano-biofortification? What are the challenges of nano-biofortification during and post of the COVID-19?
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