Albendazole Research Articles

Experimental treatment of cystic echinococcosis: Combination therapy with carvacrol and thymol versus albendazole

Cystic echinococcosis is a worldwide zoonotic disease caused by Echinococcus granulosus sensu lato (s.l.), which produces serious health and economic problems.For human treatment, chemotherapy with albendazole (ABZ), a derivative of benzimidazoles, is widely used. However, due to its low efficacy and the lack of alternatives to ABZ, novel compounds are urgently needed. Aromatic plants exhibit powerful pharmacological activities, are accessible, have a relatively low cost, and have generally mild toxicities, making them an effective choice to traditional therapies. In particular, the pharmaceutical properties of aromatic plants are partially attributed to essential oils (EOs). The aim of the present study was to assess the in vitro and in vivo effects of the combined carvacrol and thymol against E. granulosus sensu stricto (s.s.). The greatest protoscolicidal effect was observed with the 9:1 and 5:5 (carvacrol:thymol) combinations which caused a marked decrease in viability after 6 days post-incubation, agreeing with the ultrastructural changes obtained. Permeation of the cysts and loss of turgidity was observed with the incubation with the different combinations of carvacrol:thymol. In the clinical efficacy study, the combination of thymol (40 mg/kg) and carvacrol (40 mg/kg) caused a tendency to diminish the weight of the cysts in comparison with the control group. On the other hand, the treatment of infected mice with ABZ, thymol or carvacrol, caused a significant decrease in the weight of the cysts. In conclusion, we here demonstrated the efficacy of different concentrations of combined carvacrol and thymol against E. granulosus s.s. protoscoleces and murine cysts, where short periods of treatment were sufficient to achieve a pharmacological effect. Moreover, we observed a reduction in the weight of the cysts in experimentally infected mice after treatment with carvacrol and thymol.The strategy used has an advantage over synthetic drugs because natural compounds are generally safe and non-toxic. Moreover, the combination of two drugs with different modes of action would cause a reduction in the doses and treatment times. Based on the promising results obtained in vitro, in the future, different doses of the combined drugs will be assayed in vivo to determine the potential of these compounds for the treatment of cystic echinococcosis.

An Electrochemical Sensor for the Detection of Albendazole Using Glassy Carbon Electrode Modified with Platinum-Palladium Nanocomposites.

An electroanalytical electrode for the detection of albendazole (ABZ) active ingredient in pharmaceutical dosage form and in contaminated animal-derived products was developed using a glassy carbon electrode modified with platinum-palladium nanoparticles. The electro-catalytic performance of the bimetallic-modified glassy carbon electrode was compared with its bare counterpart. Under optimized conditions, the modified electrode revealed two well-resolved anodic peak currents at 1.10 and 1.23 V using differential pulse voltammetry. Pure ABZ, as well as ABZ in spiked foods (milk and chicken), were detected with little interference from the food matrix. This electrode demonstrated high sensitivity and applicability, with a lower limit of detection of 0.08 µmol L-1 in aqueous solution and 10 µmol L-1 in the contaminated ground chicken and 100 µmol L-1 in the contaminated milk sample. The fabricated sensor is low in cost and appropriate for the estimation of albendazole in tablet dosage forms and biological samples, and so can act as a quality control tool in the pharmaceutical and food industry.

In vitro efficacy of albendazole-loaded β-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto

BackgroundCystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo. MethodsWe evaluated the apoptotic effects of ABZ-loaded β-cyclodextrin (ABZ-β-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-β-CD groups. To assess the treatment efficacy of ABZ-β-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. ResultsA significant scolicidal activity of ABZ was observed only at a concentration of 800 μg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 μg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 μg/mL ABZ-β-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 μg/mL ABZ-β-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 μg/mL ABZ-β-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs. ConclusionsIn the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 μg/mL ABZ-β-CD compared to ABZ alone. This provides new insights into the use of nanostructured β-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.

Calycosin attenuates Angiostrongylus cantonensis-induced parasitic meningitis through modulation of HO-1 and NF-κB activation.

Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole (ABZ) kills nematode larvae in the brain. However, dead larvae can trigger a severe inflammatory response, resulting in brain damage. Accumulating evidence suggests that calycosin represents a potential anti-inflammatory therapeutic candidate. In this study, we investigated the combined effects of ABZ and calycosin in angiostrongyliasis caused by A. cantonensis in BALB/c mice. Inflammatory mediators (such as phospho-nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinase-9, tumour necrosis factor-α and interleukin-1β) are associated with the development of meningitis and immune inflammatory reactions. We found that A. cantonensis significantly induces inflammatory mediator production and increases the blood–brain barrier (BBB) permeability. However, co-administration of both ABZ and calycosin markedly suppressed meningitis and inflammatory mediator production and decreased the BBB permeability compared to treatment with a single drug. Furthermore, calycosin and ABZ plus calycosin treatment facilitated production of the antioxidant haem oxygenase-1 (HO-1). Moreover, co-therapy with ABZ and calycosin failed to mitigate angiostrongyliasis in the presence of tin-protoporphyrin IX, an HO-1-specific inhibitor. This finding suggests that the beneficial effects of ABZ plus calycosin treatment on the regulation of inflammation are mediated by the modulation of HO-1 activation. The present results provide new insights into the treatment of human angiostrongyliasis using co-therapy with ABZ and calycosin.

Assessment of the progress toward elimination of lymphatic filariasis in the Federal Capital Territory- Abuja, Nigeria

Lymphatic filariasis (LF) is a neglected tropical disease caused by threadlike worms (nematodes) that live in the lymphatic vessels of humans. Although three species of filarial parasites (Wuchereria bancrofti, Brugia malayi and Brugia timori) infect humans; 90% of infection is caused by Wuchereria Bancrofti and humans are its exclusive host. Nigeria is one of over 70 countries endemic for Lymphatic filariasis with an estimated 134 million people at the risk of infection. The Federal Capital Territory (FCT), which is endemic for LF, commenced mass drug administration (MDA) using ivermectin (IVM) and albendazole (ALB) in 2011. While MDA is continuing in two Area Councils, in 2020, we assessed the impact of MDA on LF prevalence in two area councils that had achieved five effective annual rounds of MDA. In 2010, a baseline mapping exercise was conducted in all six area councils of FCT-Abuja. The results revealed that four out of the six area councils were endemic for LF, with prevalence ranging from 1.0%-4.0%. The number of persons treated with ivermectin and albendazole in the four Area Councils was documented during annual MDA and population-based cluster surveys were conducted at least once in each area council during the five years of treatment, to verify the reported geographic and programme MDA coverage. This is the number treated divided by the total population eligible to receive treatment (usually <5years). The survey results confirmed that in two area councils (Abaji and Kuje) the coverage exceeded the target of 65% the while two other Councils did not reach the recommended coverage. A pre-transmission assessment survey (pre-TAS) was conducted in one sentinel site and at least one spot check site in Abaji and Kuje in 2019 and were found to have LF antigenemia (LF Ag) < 2% (range 0.0% to 1.99%). In 2020, transmission assessment surveys (TAS) were conducted in the two area councils that previously passed the Pre-transmission assessment survey. The results showed that the two Evaluation units had achieved the LF Ag threshold required to stop MDA. FCT has made significant progress towards LF elimination with two Area Councils qualifying to stop treatment. However, two other area councils still require a further two years of mass drug administration with effective MDA coverage before these area councils qualify for impact assessment.

Albendazole exerts an anti-hepatocellular carcinoma effect through a WWOX-dependent pathway

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths. The WW-domain containing oxidoreductase (WWOX) protein suppresses carcinogenesis and its absence is closely related to aggressive HCC phenotypes. In this study, by using SPR analysis, cell viability assay and xenograft mice models, we found that albendazole (ABZ), a safe and effective anthelmintic drug, exhibited the binding affinity with WWOX protein and potential inhibition effect on HCC cells in vitro and in vivo. Overexpression and knockdown of WWOX confirmed that the suppression of HCC by ABZ. Flow cytometric analysis, western blotting analysis and Co-IP were conducted to study the mechanism of ABZ. Our data showed that ABZ regulated the interaction between WWOX and its binding proteins including p53 and C-MYC. Furthermore, ABZ triggered p53-induced intrinsic apoptosis and suppressed EMT-mediated migration by C-MYC/Fibronectin axis. In addition, ∆NP73 expression was significantly inhibited by ABZ, which further sensitized p53-induced intrinsic apoptosis and cell cycle arrest. In summary, ABZ could suppress the proliferation and migration of HCC cells by regulating WWOX-dependent signaling pathway.

Comparison of local ablation with Albendazole or laparoscopic hepatectomy combined with Albendazole in the treatment of early hepatic alveolar echinococcosis.

BackgroundEchinococcosis (E) is a zoonotic parasitic disease caused by the larval morphology of echinococcosis tapeworms. Among the recognized species, two are of medical importance—E. granulosus and E. multilocularis—causing cystic echinococcosis (CE) and alveolar echinococcosis (AE) in humans, respectively. Diagnosis of AE is based on clinical manifestation and epidemiological data, imaging techniques, histopathology and/or nucleic acid detection, and serology. At present, WHO guidelines suggest that benzimidazoles (BMZ) are mandatory in all AE patients, temporarily after complete resection of the lesions and for life in all other AE cases. Interventional procedures should be preferred to palliative surgery whenever possible, and radical surgery is the first choice in all cases suitable for total resection of the lesion. However, some research centers have proposed that local ablation (LA) including radiofrequency ablation (RFA) and microwave ablation (MWA) is no less effective than radical surgery or better than simple medication in the early stage hepatic AE (WHO-IWGE PNM classification of AE: P1N0M0). This study attempted to compare the real efficacy of the above treatment methods, so as to find the best treatment for this kind of patient.MethodsThe data of patients with hepatic AE who underwent laparoscopic hepatectomy (LH), RFA, and MWA in Qinghai Provincial People's Hospital from January 2015 to January 2021 were collected. At the same time, the cases treated with Albendazole (ABZ) were collected together with the institution for disease control and prevention. According to the treatment methods, the above cases were divided into LH group, RFA group, MWA group, and medication group. The basic data and postoperative recovery indices of the four groups were compared, respectively.ResultsA total of 199 patients with hepatic AE were enrolled in this study, including 90 males and 109 females. The youngest was 5 years old and the oldest was 66 years old, with an average of 33.41±14.64 years old. 20.6% of the patients had hepatitis B (41/ 199). A total of 45 patients underwent ultrasound-guided RFA, 47 patients underwent ultrasound-guided MWA, 51 patients were treated with ABZ, and 56 patients underwent LH. There were no significant differences in baseline characteristics among the four groups (p > 0.05). The RFA group and MWA group were more advantageous than the LH group regarding operation time and incidence of postoperative complications (p < 0.05). But recurrence rate of the lesion in the LH group was significantly lower than the RFA group, MWA group, and medication group. However, there was no significant difference in recurrence-free survival time among the four groups (p >0.05).ConclusionLH has a significant effect in the treatment of early-stage hepatic AE, especially in terms of recurrence which is significantly better than LA and medication alone. Follow-up and adherence to ABZ therapy are essential if conservative treatment is to achieve better outcomes.

An ultrahigh-performance liquid chromatography-fluorescence detection (UHPLC-FLD) method for simultaneous determination of albendazole and its three metabolites in poultry eggs

Albendazole (ABZ) is widely used in the treatment of animal intestinal parasitic infections. This study has established a method of ultrahigh-performance liquid chromatography coupled with fluorescence detection for the simultaneous determination of ABZ and its three metabolites (albendazole, albendazole sulfone, albendazole sulfoxide, albendazole-2-aminosulfone) in poultry (chicken, duck, and goose) eggs. Good linearity was shown under the optimized conditions with the determination coefficient (≥ 0.9994). The limits of detection (LOD) were 0.3–4.6 µg/kg, whereas the limits of quantification (LOQ) were 1.0–12.9 µg/kg. The recoveries of ABZ and its three metabolites ranged from 80.5% to 98.6%, while relative standard deviations were in the range of 1.2–4.8%, and all target analytes could be detected within 6 min. The method was demonstrated to be sensitive, selective, and quick for the detection of ABZ and its three metabolites.

Giardia duodenalis: Flavohemoglobin is involved in drug biotransformation and resistance to albendazole.

Giardia duodenalis causes giardiasis, a major diarrheal disease in humans worldwide whose treatment relies mainly on metronidazole (MTZ) and albendazole (ABZ). The emergence of ABZ resistance in this parasite has prompted studies to elucidate the molecular mechanisms underlying this phenomenon. G. duodenalis trophozoites convert ABZ into its sulfoxide (ABZSO) and sulfone (ABZSOO) forms, despite lacking canonical enzymes involved in these processes, such as cytochrome P450s (CYP450s) and flavin-containing monooxygenases (FMOs). This study aims to identify the enzyme responsible for ABZ metabolism and its role in ABZ resistance in G. duodenalis. We first determined that the iron-containing cofactor heme induces higher mRNA expression levels of flavohemoglobin (gFlHb) in Giardia trophozoites. Molecular docking analyses predict favorable interactions of gFlHb with ABZ, ABZSO and ABZSOO. Spectral analyses of recombinant gFlHb in the presence of ABZ, ABZSO and ABZSOO showed high affinities for each of these compounds with Kd values of 22.7, 19.1 and 23.8 nM respectively. ABZ and ABZSO enhanced gFlHb NADH oxidase activity (turnover number 14.5 min-1), whereas LC-MS/MS analyses of the reaction products showed that gFlHb slowly oxygenates ABZ into ABZSO at a much lower rate (turnover number 0.01 min-1). Further spectroscopic analyses showed that ABZ is indirectly oxidized to ABZSO by superoxide generated from the NADH oxidase activity of gFlHb. In a similar manner, the superoxide-generating enzyme xanthine oxidase was able to produce ABZSO in the presence of xanthine and ABZ. Interestingly, we find that gFlHb mRNA expression is lower in albendazole-resistant clones compared to those that are sensitive to this drug. Furthermore, all albendazole-resistant clones transfected to overexpress gFlHb displayed higher susceptibility to the drug than the parent clones. Collectively these findings indicate a role for gFlHb in ABZ conversion to its sulfoxide and that gFlHb down-regulation acts as a passive pharmacokinetic mechanism of resistance in this parasite.

Highly sensitive electro-oxidative voltammetric determination of anthelmintic drug albendazole using porous graphitic carbon nitride sensor infused with cationic micellar solution

A sensitive and novel electrochemical senser, acetyl trimethylammonium bromide (CTAB)-immobilized nitrogen rich g-C3N4 nanosheet modified carbon paste electrode was developed, for the electrochemical investigation of the anthelmintic drug Albendazole (ABZ) using voltammetric tools like cyclic and square wave voltammetry. The results showed that the modified carbon paste electrode exhibited remarkable electro-catalytic action towards the electrochemical oxidation of ABZ in a phosphate buffer solution at pH 3 compared to bare carbon paste electrode. The electrode material was characterized by CV, scanning electron microscopy (SEM), atomic force microscope (AFM), and electrochemical impedance spectroscopy (EIS). A highly sensitive square wave voltammetric technique was developed for the determination of ABZ, at a trace level with great precision and accuracy, good limit of detection (LOD) 0.01 µM and limit of quantification (LOQ) of 0.036 µM, in the concentration range of 0.2–10 µM. This approach can be used in pharmaceutical formulations for clinical diagnosis, quality assurance, and drug screening. In addition, this technique is also implemented for the assessment of ABZ in water samples and biological samples like urine and blood plasma.

Antiparasitic Effects of Asteraceae Species Extracts on Echinococcus granulosus s.s.

Cystic echinococcosis is a zoonotic disease caused by the parasite Echinococcus granulosus sensu lato (s.l.), which is worldwide distributed and causes long-lasting infections in animals and humans. The existing treatment is limited to the use of benzimidazoles, mainly albendazole (ABZ). However, it has unwanted side effects and its efficacy is about 50%. The Asteraceae family includes plants that have therapeutic applications (medicinal species) and has an important role in new drug development. The species belonging to a different genus of this family show a wide range of anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, and antiparasitic activities, among others. The aim of the present study was to evaluate the in vitro efficacy of extracts of four Asteraceae species against protoscoleces of E. granulosus sensu stricto (s.s.). On the other hand, the Stevia aristata extract was assessed on the murine cyst of E. granulosus (s.s.) and the efficacy of S. aristata extract was investigated in a murine model of CE. Stevia satureiifolia, S. aristata, Grindelia pulchella, and G. chiloensis extracts at 100 μg/mL caused a decrease in protoscoleces viability; however, S. aristata extract produced the greatest in vitro protoscolicidal effect. After 20 days of treatment with the highest concentration (100 μg/mL) of S. aristata extract, protoscoleces viability decreased to 0%. The tegumental changes observed by scanning electron microscopy were consistent with the reduction in vitality. The collapse of the germinal layer was registered in 60 ± 5.8% and 83.3 ± 12.0% of cysts treated during 4 days with 50 and 100 μg/ml, respectively. The half maximal effective concentration (EC50) value of the S. aristata extract against E. granulosus (s.s.) cysts was 47.86 μg/mL (96 h). The dosage of infected animals with the 50 mg kg−1 dose of S. aristata extract resulted in a significant reduction in cyst weight in comparison with the control group. In conclusion, S. aristata extract was demonstrated to exert a marked effect, both in vitro and in the murine model.

Pharmacological characterization of geraniol in sheep and its potential use in the control of gastrointestinal nematodes

Geraniol (GNL) was effective against gastrointestinal nematodes in vitro; nevertheless, the anthelmintic effect of phytochemicals combined with synthetic drugs has been little explored in vivo. This article characterized in vitro / in vivo the pharmacological features of GNL in sheep as well as its pharmacokinetic interaction with albendazole (ABZ). Additionally, the in vivo efficacy of GNL against Haemonchus contortus was evaluated in lambs. Liver microsomes from lambs were incubated in the absence or presence of GNL to analyze CYP1A1, CYP1A2 and FMO metabolic pathways. The effect of GNL on the hepatic sulfoxidation and sulfonation of ABZ and the ruminal sulforeduction of albendazole sulfoxide (ABZSO) was assessed. The in vivo pharmacokinetic interaction of ABZ and GNL was evaluated in lambs. The effect of GNL on the fecal egg count was evaluated in lambs infected with a resistant isolate of H. contortus. In sheep liver microsomes, the presence of 2 mM GNL reduced the CYP1A1, CYP1A2 and FMO pathways by 77.9, 90.8 and 84.5%, respectively, with respect to control (P < 0.05). In the presence of 2 mM GNL, the ABZ sulfoxidation decreased from 114.4 ± 8.49 (control) to 50.24 ± 11.1 nmol/min.mg, and ABZSO2 production decrease from 0.52 ± 0.14 to 0.09 ± 0.03 nmol/h.mg. No changes in the pharmacokinetic behavior of ABZ were observed in the presence of GNL. The in vivo efficacy of four doses of GNL was 40.5%. These findings highlight the importance of integrated in vitro / in vivo pharmaco-parasitological studies to develop new pharmacological tools for controlling gastrointestinal parasites.

Adverse drug effects among students following mass de-worming exercise involving administration of Praziquantel and Albendazole in KEEA Municipality, Ghana.

To manage the deleterious effects of parasitic infections such as lymphatic filariasis (LF) and schistosomiasis among school children, most countries including Ghana make use of mass drug administration (MDA). Although MDA has proven effective in reducing worm burden, unfortunately adverse drug effects (ADEs) post-MDA are derailing the gains and also remain poorly monitored. The study assessed incidence and factors associated with ADEs among students following a school-based mass de-worming exercise involving administration of Praziquantel (PZQT) and Albendazole (ADZ) against LF and SCH at Komenda-Edina-Eguafo-Abirem (KEEA) Municipal. After fulfilling all ethical obligations, a total of 598 students aged 5-20 years who received PZQT or ADZ monotherapy or a combination of the two (PZQT + ADZ) as part of the mass de-worming exercise were recruited through quota and random sampling. Bodyweight and height of students were measured and body mass index (BMI) calculated. Students were orally interviewed to obtain information such as age, sex, intake of diet before taking drugs. Subsequently, students were monitored over 24 hours post-MDA for cases of ADEs. Descriptive statistics and logistic regression analysis using SPSS version 26 was used to describe data collected and to determine associations between incidence of ADEs and predictor variables. Out of the 598 students, 243 (40.64%) represented by 124 males (51.03%) and 119 females (48.97%) with mean (SD) age of 13.43 (2.74) years experienced one or more forms of ADE. In decreasing order, the detected ADEs included headache (64.6%), Abdominal pain (48.6%), fever (30.0%), diarrhea (21.4%) and itching (12.8%). Multivariable statistical analysis showed that age 5-9 years (OR: 2.01, p = 0.041) and underweight (OR: 2.02, p = 0.038) were associated with incidence of ADEs. Compared with students who received combination therapy, students who received ADZ only (OR: 0.05, p < 0.001) and PZQT only (OR: 0.26, p < 0.001) had low cases of ADEs. Gender and diet intake before MDA were not associated with ADE incidence. ADE incidence was common among students in the KEEA municipality. Age, underweight, and double dosing were associated with increase in ADE incidence, while gender and food intake were not associated with increase in ADE incidence. The Disease Control Unit of the Ghana Health Service should incorporate stringent ADE monitoring in post-MDA surveillance in the National MDA program in order to be able to detect, manage and report ADEs to inform planning for future MDA programs. Such initiatives will help not only in improving effectiveness of MDA programs but also identify high risk groups and exact strategies to reduce negative influence of ADE on MDA coverage and anthelminthic drug compliance.

Nanocrystal Suspensions for Enhancing the Oral Absorption of Albendazole.

Albendazole (ABZ), an effective benzimidazole antiparasitic drug is limited by its poor solubility and oral bioavailability. In order to overcome its disadvantages, ABZ nanocrystals were prepared using a novel bottom-up method based on acid-base neutralization recrystallization with high-speed mixing and dispersing. The cosolvent, stabilizer and preparation temperature were optimized using single factor tests. The physicochemical properties, solubility and pharmacokinetics of the optimal ABZ nanocrystals were evaluated. The high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) showed that ABZ had no structural and crystal phase change after nanocrystallization. The saturated solubility of ABZ nanocrystals in different solvents was increased by 2.2–118 fold. The oral bioavailability of the total active ingredients (ABZ and its metabolites of albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2)) of the nanocrystals in rats was enhanced by 1.40 times compared to the native ABZ. These results suggest that nanocrystals might be a promising way to enhance the solubility and oral bioavailability of ABZ and other insoluble drugs.

Potential therapeutic effect of platelet-rich plasma and albendazole on the muscular phase of experimental Trichinella spiralis infection

Trichinellosis is a food-borne parasitic infection causing muscle damage. This study aimed to detect the potential therapeutic effect of platelet-rich plasma (PRP) alone or in combination with albendazole (ALB) on the muscular phase of experimental Trichinella infection in rats. The study was conducted on 70 rats divided into four main groups: healthy non-infected non-treated rats, non-infected rats treated with PRP, infected untreated rats (seven rats in each group), and an infected group of 49 rats. The infected group was further subdivided based on the drug therapy received. The effects of drug therapy were evaluated using parasitological and histopathological analyses.The percent reduction in the number of Trichinella spiralis larvae per gram of muscle in the PRP-treated groups (one, two, and three doses) was 43.1%, 78.8%, and 86.1%, respectively. Groups treated with combined therapy of ALB & PRP (one, two, and three doses) showed overall reduction percentages of 87.7%, 90.9% and 95.2%, respectively. In contrast, the ALB-treated group showed a 69.4% reduction. All results of the abovementioned groups were statistically significant compared to the control-infected non-treated group.The findings of the histopathological analysis were consistent with the parasitological results. Groups receiving combined therapy showed the most significant improvement in terms of the degree of inflammation and fibrosis. It can be concluded that PRP has a modulatory effect on the pathology caused by T. spiralis larvae in the muscular phase of trichinellosis.To our knowledge, this is the first study to investigate the effect of PRP on the muscular phase of T. spiralis infection.

Albendazole-induced autophagy blockade contributes to elevated apoptosis in cholangiocarcinoma cells through AMPK/mTOR activation

Albendazole (ABZ) is a broad-spectrum anti-parasitic drug that exhibits antitumor effects against several carcinomas. The effects of ABZ on cholangiocarcinoma (CCA) and its underlying mechanisms are still unclear. Our study aims to investigate the role of ABZ in inducing autophagy-mediated apoptosis of cholangiocarcinoma cells. The antitumor effects of ABZ were evaluated against CCA cells and HIBEC intrahepatic biliary epithelial cells. Furthermore, the apoptosis rates, and autophagy flux in RBE and FRH-0201 cells treated with ABZ were investigated. ABZ inhibited proliferation, induced cell death and apoptosis in CCA cells in vitro. In vivo, tumors from ABZ- treated BALB/c nude mice were significantly smaller than untreated mice. ABZ also induced the initiation of autophagy via AMPK/mTOR pathways, resulting in the formation of autophagosome. In addition, ABZ blocked autophagic flux by inhibiting the fusion of autophagosome-lysosome, which increased the apoptotic death of CCA cells. However, the apoptotic death of CCA cells induced by ABZ was reversed by 3-methyladenine (3-MA), an autophagosome formation inhibitor, but increased by chloroquine (CQ), an autophagosome-lysosome fusion inhibitor.Our work provides novel mechanisms for anti-tumor effects of ABZ on CCA, suggesting that ABZ may be used as a potent autophagy inhibitor in the treatment of CCA.

Formulation, in-vitro and ex-vivo evaluation of albendazole loaded ufasomal nanoformulation for topical delivery

Albendazole (ABZ), a widely used anti-parasitic agent, has recently drawn considerable attention due to its wide variety of therapeutic activities, such as anticancer and anti-psoriasis properties. However, its low water solubility limits its clinical applicability. The aim of the current study was to prepare ABZ loaded ufasomes (ABZ-U) to improve drug solubility and permeation through skin for topical delivery. ABZ-U was formulated by a thin film hydration and homogenization technique. Optimized ABZ-U was characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The formulation was further incorporated into a ufasomal gel base (ABZ-UG) and evaluated for drug release, rheology, and skin deposition. The optimized nanovesicles presented small particles size (235.71 ± 33.77 nm), good PDI (0.192 ± 0.088), acceptable zeta potential (−67.46 ± 2.35 mV) and entrapment efficiency of 74.14 ± 0.70%. The hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. Analyzing in vitro drug release study by various mathematical models, the optimized ABZ-UG showed a zero-order release pattern with 99.86 ± 0.79% cumulative ABZ release within 24 h. Ex vivo permeation studies across Wistar rat skin indicated suitable skin retention of ABZ for topical delivery. Overall, the study proved that ABZ-UG could be a promising carrier in treatment of skin diseases.

Dual inhibition of glucose uptake and energy supply synergistically restrains the growth and metastasis of breast cancer

Metastatic breast cancer (MBC) is one of the most common and knotty diseases in female population which could place them in a life-threatening condition. For malignant proliferation and migration, cancer cells require a large amount of glucose and energy to meet the demand of rapid metabolism. Hence, efficiently diminishing the utilization of energy substances by cancer cells is emerging as validated therapeutic strategies for cancer therapy. Herein, a nanoplatform with dual-inhibition of glucose uptake and oxidative phosphorylation (OXPHOS) was designed, which consisted of albendazole (ABZ) and atovaquone (ATO) by simple carrier-free self-assembling. The introduction of ABZ could evidently decrease glucose uptake to reduce the main “energy fuel” of cancer cells. Meanwhile, as a blocker of OXPHOS, ATO would reduce adenosine triphosphate (ATP) production and ameliorate hypoxia microenvironment by suppressing mitochondrial respiratory chain. Under such dual inhibition of energy metabolism, AA NPs exerted synergistic energy exhaustion effect and outstanding hypoxia improvement function, efficiently inhibiting tumor growth and metastasis. This research not only illustrates the feasibility of energy metabolism therapy by co-inhibiting glucose uptake and OXPHOS, but also provides an ingenious tactic to diminish metastasis during MBC treatment

Loa loa in the Vitreous Cavity of the Eye: A Case Report and State of Art.

ABSTRACT.Loa loa is a filarial nematode responsible for loiasis, endemic to West–Central Africa south of the Sahara and transmitted by flies. This study reports a case of L. loa in the vitreous cavity of the eye of a young patient, along with an in-depth literature review. A 22-year-old woman from Cameroon who migrated from Cameroon to Italy was referred to the Emergency Ophthalmology Department at Policlinico di Bari in July 2021 with the presence of a moving parasite in the subconjunctiva of the left eye. A recent onset of a papular lesion on the dorsal surface of the right wrist and a nodular lesion in the scapular region were detected. L. loa filariasis was diagnosed based on anamnestic data, clinical and paraclinical signs, and a parasitological test confirming the presence of microfilariae in two blood samples collected in the morning of two different days. Because of the unavailability of diethylcarbamazine (DEC), albendazole (ALB) 200 mg twice daily was administered for 21 days. A mild exacerbation of pruritus occurred during treatment, but resolved with the use of an antihistamine. A single dose of 12 mg ivermectin was prescribed at the end of the treatment with albendazole. Unlike other endemic parasite infections, L. loa is not included in the Global Program to Eliminate Lymphatic Filariasis, because it is not mentioned in the WHO and CDC list of neglected tropical diseases. This can result in an overall risk of lack of attention and studies on loiasis, with lack of data on global burden of the disease.

A Retrospective Study of the Efficacy of Albendazole and Diethylcarbamazine for the Treatment of Human Toxocariasis.

In the Department of Parasitology and Mycology of Toulouse University Hospitals, patients presenting with common/covert toxocariasis were treated either with albendazole (39 cases) or with diethylcarbamazine (32 cases). Albendazole (ABZ) was given at 10 mg/kg b/w daily for 14 days, and diethylcarbamazine (DEC) was given at 4 mg/kg b/w daily for 21 days. In both groups, follow-up consultations occurred approximately 48 days after the end of the anthelmintic therapy. ABZ and DEC displayed a similar efficacy on the kinetics of the clinical picture (−64.5% of reduction vs. −72.7%, respectively) and on the levels of blood eosinophilia, serum eosinophil cationic protein and serum total IgE. However, the effect of the medication on the laboratory parameters was moderate. The rate of adverse reactions was similar in both groups (38% for ABZ vs. 31% for DEC), but DEC-treated patients complained of more intense and long-lasting side effects. The DEC group had more major adverse reactions, resulting in the termination of the anthelmintic treatment. The results from this retrospective study bring further arguments for considering ABZ, given at 10 mg/kg daily for 2 weeks, as the drug of choice in the treatment of human toxocariasis.