Fenpropathrin, a pyrethroid insecticide, has been widely used for many years in agricultural fields. It works by disturbing the voltage-gated sodium channel, leading to paralysis and the death of the target animal. While past studies have focused on neurodegeneration following fenpropathrin poisoning in humans, relatively few pieces of research have examined its effect on other peripheral organs. This study successfully investigated the potential toxicity of fenpropathrin on the cardiovascular system using zebrafish as an animal model. Zebrafish larvae exposed to varying doses of fenpropathrin underwent an evaluation of cardiac physiology by measuring the heart rate, stroke volume, cardiac output, and shortening fraction. The blood flow velocity and the dorsal aorta diameter were also measured to assess the impact of fenpropathrin exposure on the vascular system. Furthermore, molecular docking was performed to evaluate the pesticide binding affinity to various proteins associated with the cardiovascular system, revealing the potential mechanism of the fenpropathrin cardiotoxic effect. The findings demonstrated a significant dose-dependent increase in the heart rate stroke volume, cardiac output, shortening fraction, and ejection fraction of zebrafish larvae after 24 h of acute treatment with fenpropathrin. Additionally, zebrafish treated at a concentration of 1 ppm exhibited significantly larger blood vessels in diameter and an increased blood flow velocity compared to the control group. According to molecular docking, fenpropathrin showed a high affinity for various voltage-gated sodium channels like scn1lab, cacna1sb, and clcn3. Finally, from the results, we found that fenpropathrin caused cardiomegaly, which may have been induced by the voltage-gated sodium channel disruption. This study highlights the significant disruption of fenpropathrin in the cardiovascular system and emphasizes the need for further research on the health implications of this pesticide.

P-Toluene sulfonamide (p-TSA), a small molecular drug with antineoplastic activity is widely gaining interest from researchers because of its pharmacological activities. In this study, we explored the potential cardio and neural toxicity of p-TSA in sublethal concentrations by using zebrafish as an in vivo animal model. Based on the acute toxicity assay, the 96hr LC₅₀ was estimated as 204.3 ppm, suggesting the overall toxicity of p-TSA is relatively low in zebrafish larvae. For the cardiotoxicity test, we found that p-TSA caused only a minor alteration in treated larvae after no overall significant alterations were observed in cardiac rhythm and cardiac physiology parameters, as supported by the results from expression level measurements of several cardiac development marker genes. On the other hand, we found that acute p-TSA exposure significantly increased the larval locomotion activity during the photomotor test while prolonged exposure (4 days) reduced the locomotor startle reflex activities in zebrafish. In addition, a higher respiratory rate and blood flow velocity was also observed in the acutely treated fish groups compared to the untreated group. Finally, by molecular docking, we found that p-TSA has a moderate binding affinity to skeletal muscle myosin II subfragment 1 (S1), ATPase activity, actin- and Ca²⁺-stimulated myosin S1 ATPase, and v-type proton ATPase. These binding interactions between p-TSA and proteins offer insights into the potential molecular mechanism of action of p-TSA on observed altered responses toward photo and vibration stimuli and minor altered vascular performance in the zebrafish larvae.

BCR-ABL, a fusion protein kinase, is a druggable target exclusively expressed in patients with chronic myeloid leukemia (CML). Several anti-leukemia medicines targeting this protein have been developed in recent years. However, therapeutic options are limited for CML patients bearing multiple BCR-ABL1 mutations. Ponatinib (PON), a potent tyrosinase inhibitor, was one of the approved drugs for managing BCR-ABL1 T315I mutant disease. However, treatment of patients with PON reported severe side effects related to cardiovascular events. Asciminib (ASC) was the first allosteric inhibitor approved to target the myristoyl pocket of BCR-ABL protein to inhibit protein activity. The different mechanism of inhibition opens the possibility of co-exposure with both medicines. Reports on cardiovascular side effects due to the combination use of PON + ASC in pre-clinical and clinical studies are minimal. Thus, this study aimed to observe the potential cardiovascular-related side effect after co-exposure to ASC and PON using zebrafish as an animal model. In this study, zebrafish were acutely exposed to both compounds. The cardiovascular physiology parameters and gene expression related to cardiovascular development were evaluated. We demonstrate that combining ASC with PON at no observed effect concentration (NOEC) did not cause any significant change in the cardiac performance parameter in zebrafish. However, a significant increase in nkx2.5 expression level and a substantial decrease in blood flow velocity were recorded, suggesting that combining these compounds at NOEC can cause mild cardiovascular-related side effects.

Objective. This study aimed to identify problems and highlight opportunities for pharmaceutical sciences research in the Philippine pharmaceutical industry's regulatory and clinical research sectors that might have been previously overlooked or underrepresented. It identified current issues that can be addressed by research covering four areas of pharmaceutical sciences: drug design and discovery, pharmacokinetic/pharmacodynamic studies, formulation design and pharmaceutical technology, and regulatory science. Methods. A descriptive qualitative approach was used in this study. Data collection was facilitated by key informant interviews (KII) using a standardized interview guide with open-ended questions to identify the pharmaceutical science research needs of the specific sectors. A purposive sampling method was employed, with five key informants (KIs), including the company vice president, director, and top-level managers from different local and multinational pharmaceutical companies. ATLAS.ti software was utilized to facilitate thematic synthesis for qualitative data analysis. Results. Thirteen common themes were identified from the KIs, such as (1) incomplete development of therapeutic compounds, (2) sustainability of raw materials supply, (3) regulation of herbal medicines versus food supplements, (4) mapping disease priorities through the Philippine pharmaceutical roadmap, (5) government incentives and policies to support research, (6) technical personnel, (7) suboptimal regulatory process, approvals, and implementation, (8) gap in utilization of acquired knowledge on regulations, (9) regulatory governance, (10) passive regulatory action on counterfeit drugs, (11) PIC/S GMP version 14 adaption, (12) formulation optimization, and (13) active pharmaceutical ingredient (API) sourcing and regulation. Based on insights from the International Pharmaceutical Federation regarding anticipated hurdles in pharmaceutical sciences over the next 5-10 years, priority research needs were identified through KIs' input. Relevant action plans were developed, including the creation of research proposals to isolate, purify, and determine chemical structures of natural products, as well as analyzing recent Philippine Health Statistics to help assess the appropriateness of new drug releases for patient needs. Other action plans include forecasting future disease burdens in the country, performing toxicology studies (Health-Based Evaluation Levels/No Observed Adverse Effect Level or HBEL/NOAEL) for common generic drugs, and ensuring that research efforts are directed toward addressing the Philippine pharmaceutical regulatory and clinical research sector's most pressing needs practically and feasibly. Conclusion. This study offers valuable insights into pharmaceutical sciences research and development initiatives within the regulatory and clinical research sectors in the Philippine pharmaceutical industry. These findings have the potential to catalyze transformative advancements in healthcare delivery and outcomes, positioning the Philippines for global excellence and competitiveness.