DARU Journal of Pharmaceutical Sciences最新文献

Objectives: Sometimes clinical efficacy and potential risk of therapeutic and toxic agents are difficult to predict over a long period of time. Hence there is need for literature search with a view to assessing cause of toxicity and less efficacy of drugs used in clinical practice.

Method: Hence literatures were searched for physicochemical properties, chemical formulas, molecular masses, pH values, ionization, receptor type, agonist and antagonist, therapeutic, toxic and structure-activity relationship of chemical compounds with pharmacophore and toxicophore, with a view to identifying high efficacious and relative low toxic agents. Inclusion criteria were manuscripts published on PubMed, Scopus, Web of Science, PubMed Central, Google Scholar among others, between 1960 and 2023. Keywords such as pharmacophore, toxicophore, structure-activity-relationship and disease where also searched. The exclusion criteria were the chemicals that lack pharmacophore, toxicophore and manuscripts published before 1960.

Results: Findings have shown that pharmacophore and toxicophore functional groups determine clinical efficacy and safety of therapeutics, but if they overlap therapeutic and toxicity effects go concurrently. Hence the functional groups, dose, co-administration and concentration of drugs at receptor, drug-receptor binding and duration of receptor binding are the determining factors of pharmacophore and toxicophore activity. Molecular mass, chemical configuration, pH value, receptor affinity and binding capacity, multiple pharmacophores, hydrophilic/lipophilic nature of the chemical contribute greatly to functionality of pharmacophore and toxicophore.

Conclusion: Daily single therapy, avoidance of reversible pharmacology, drugs with covalent adduct, maintenance of therapeutic dose, and the use of multiple pharmacophores for terminal diseases will minimize toxicity and improve efficacy.

Background: Anemia affects one-fourth of the world's population and is caused mostly by iron deficiency. Iron supplementation is the most essential strategy for preventing iron deficiency anemia. Conventional oral iron salts have many drawbacks such as poor absorption & bioavailability, and poor tolerability resulting in poor clinical outcomes.

Objective: To compare the effectiveness and safety of ferrous ascorbate, ferrous fumarate, ferrous bis-glycinate, and Sucrosomial iron in the management of iron deficiency anemia.

Method: The study is a retrospective observational clinical study comprising 260 subjects with hemoglobin between 7-10 g/dl. The patients were divided into four groups I, II, III, and IV, and received ferrous fumarate, ferrous ascorbate, ferrous bis-glycinate, and Sucrosomial iron respectively. Hematological profile and iron store indices were measured at baseline and month 3. One-way ANOVA followed by Tukey multiple comparison test was used to assess statistical significance (P < 0.05) using GraphPad Prism V.9.3.1 software.

Results: The observational study showed that hemoglobin levels were significantly increased in the ferrous ascorbate group (11.86 ± 0.09; P < 0.0001), ferrous fumarate group (11.72 ± 0.08; P < 0.0001), ferrous bis-glycinate group (11.69 ± 0.11; P = 0.0003) and Sucrosomial iron group (12.20 ± 0.1; P < 0.0001) compared to the baseline. The Sucrosomial iron-supplemented group showed significantly higher improvement in hemoglobin levels and serum ferritin levels compared to conventional oral iron salts (P < 0.05) with a better safety profile.

Conclusion: The Sucrosomial iron showed significantly higher improvement in hemoglobin levels and higher improvement in iron store indices parameters along with a good tolerability profile compared to other conventional oral iron salts.

Background: Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex).

Objectives: This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity.

Methods: The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold.

Results: The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications.

Conclusion: The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20 g were divided into five groups: control, 5-FU (50 mg/kg), 5-FU + MEL (2.5, 5 & 10 mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.

Background: Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer.

Methods: Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included.

Results: According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells.

Conclusion: Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

Background: COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few.

Objectives: Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children.

Methods: We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports.

Results: The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives.

Conclusion: COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.

Background: Several countries' most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored.

Objectives: To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish's initial development.

Methods: Zebrafish embryos 6-8 h post-fertilization (hpf) were exposed to different concentrations of ACM, MTZ, and NMS, separately, to obtain the 50% lethal concentrations (LC₅₀). Next, the embryos were exposed to distinct concentrations of the cocktail (LC₅₀/2, LC₅₀/5, LC₅₀/10, and LC₅₀/20) in a semi-static system. Samples were analyzed 0, 24, 48, and 96 h after exposure, and the drugs' concentrations in E3 medium were assessed by high-performance liquid chromatography. For embryotoxicity evaluation, the mortality, hatching, and heart rates; total length; and pericardial and yolk sac areas were determined. In addition, body malformations, edemas, presence of pigmentation, and histopathological assessments were also recorded.

Results: The LC₅₀ values obtained for MTZ, ACM, and NMS were 4.69 mgmL^-1, 799.98 μgmL^-1, and 0.92 μgmL^-1, respectively. No difference was observed between the drugs' nominal and observed concentrations at each time point. The cocktail significantly induced mortality and decreased hatching in the LC₅₀/10, LC₅₀/5, and LC₅₀/2 groups. Additionally, body malformations, pigmentation loss, and yolk sac and pericardial edemas were observed in the cocktail groups. The cocktail groups' larvae had decreased total length and slower heart rates compared to the controls (p < 0.05). The histopathological assessment showed that yolk sac edema promoted severe histological changes in the esophageal-intestine junction and intestine in larvae treated with cocktails. Moreover, PAS-positive structures decreased in the esophageal-intestine junction, intestine, and liver in larvae exposed to pharmaceutical cocktails.

Conclusion: This study's findings suggest the cocktail of ACM, MTZ, and NMS may be hazardous to aquatic organisms in case of environmental contamination.

Background: Cancer treatment has improved over the past decades, but many cancer patients still experience adverse drug reactions (ADRs). Pharmacogenomics (PGx), known as personalized treatment, is a pillar of precision medicine that aims to optimize the efficacy and safety of medications by studying the germline variations. Germline variations in the DPYD lead to significant ADRs. The present cross-sectional study aims to evaluate the allele frequency of the DPYD gene variations in the Iranian population to provide insights into personalized treatment decisions in the Iranian population.

Methods: The allele frequency of 51 pharmacogenetic variations in the clinically relevant DPYD was assessed in a representative sample set of 1142 unrelated Iranian individuals and subpopulations of different ethnic groups who were genotyped using the Infinium Global Screening Array-24 BeadChip.

Results: The genotyping assay revealed eight pharmacogenetic variants including DPYD rs1801265 (c.85T > C; DPYD*9A), rs2297595 (c.496A > G), rs1801158 (c.1601G > A; DPYD*4), rs1801159 (c.1627A > G; DPYD*5), rs1801160 (c.2194G > A; DPYD*6), rs17376848 (c.1896T > C), rs56038477 (c.1236G > A; HapB3), and rs75017182 (c.1129-5923C > G; HapB3) with minor allele frequency (MAF) ≥ 1%.

Conclusion: The results of the study reveal significant genetic variations among Iranian population that could significantly influence clinical decision-making. These variants, with their potential to explain the substantial variability in drug response phenotypes among different populations, shed light on a crucial aspect of pharmacogenomics. These findings not only provide valuable insights but also inspire the design and implementation of future pharmacogenomic clinical trials, motivating further research in this crucial area.

Background: The analysis of how people search and "navigate" the internet to obtain health-related information and how they communicate and share this information can provide valuable knowledge about the disease patterns behaviour and health habits of populations.

Objective: To determine the population's interest in drug-related problems through information search trends.

Method: A descriptive ecological correlational study, based on obtaining Google Trends data.

Variables studied: relative search volume (RSV), evolution over time, milestones and seasonality.

Results: The most searched topic was drug overdose, with mean RSV of 56.25 ± 0.65. The highest increase occurred in the contraindication topic (R² = 0.87, p < 0.001). The main milestone was observed in the drug overdose topic in July 2018 (RSV = 100). A very close relationship was found between adverse drug reaction and contraindication (R = 0.89, p < 0.001). Slight seasonality was noted in the adverse drug reaction (augmented Dickey-Fuller test [ADF] = -1.96), contraindication (ADF = -2.66) and drug interaction (ADF = -1.67) topics, but did not show an epidemiological trend.

Conclusions: The greatest public interest was found in the drug overdose and contraindication topics, which showed a stronger upward trend, although the seasonality study did not show any very notable data or demonstrate epidemiological information search behaviour. The main milestone observed was due to media factors related to the consumption of narcotics. There was a clear difference in English-speaking countries in the use of the drug overdose topic. A correlation between the adverse drug reaction and contraindication topics was confirmed.