Exogenous Agents Research Articles

Label-free quantitative phase imaging and analysis of airborne pollen

Abstract Pollen morphology, involving the physical characteristics of pollen grains from seed plants during reproduction, plays an important role in plant biology, ecology, and evolution. High pollen concentrations in the air can degrade air quality and exacerbate respiratory conditions such as asthma. Understanding pollen morphology and its implications for air quality is significant for mitigating respiratory health risks. Conventionally, fluorescence microscopy is used for pollen imaging, but photobleaching, quenching, and phototoxicity affect the surface morphology and do not provide quantitative data on the pollen grains. For this study, we used bright field (BF) imaging and quantitative phase imaging (QPI), a label-free interferometric microscopy method, to look at differences in the shape of pollen. BF imaging provides information about the shape and size of the different pollens but has a limitation of low contrast. To obtain high-contrast images and quantitative data on the pollen grains without any exogenous agents, we employed QPI and BF imaging in the present study. QPI enables the extraction of detailed information regarding the cell wall, aperture, and thickness of pollen while also maintaining their natural state without the need for chemical treatments. In the present work, we sampled the ambient air from May 2023 to January 2024 on the IIT Delhi campus. Subsequently, QPI and BF imaging have been done for pollen identification and phase analysis of arboreal and non-arboreal pollen. Further, by utilizing the information obtained from BF microscopy and QPI, different species of pollen have been identified, and a pollen calendar has been prepared for exhibiting pollen season throughout the year. To the best of the authors’ knowledge, they have conducted the QPI of airborne pollen grains for the first time; this technique holds great potential for characterizing airborne pollens without the need for staining or sample preparation.

Doubled Haploid Technology: Generation of Doubled Haploid Maize Lines Using Haploid Inducers.

Doubled haploid (DH) technology allows for the development of completely homozygous lines from heterozygous plants in only two generations. This approach has been widely adopted in maize breeding programs, as it expedites the generation of inbred lines compared to traditional methods. The DH approach is based on the use of maize genotypes that have the ability to induce haploid seeds when used as the pollen parent. The most common method for producing maize haploid plants for the generation of DH lines is in vivo maternal haploid induction. The process involves pollination with a haploid inducer maize line to generate haploid seeds. Then, haploids are screened for and identified (typically via the expression of a particular marker gene), germinated, treated with an exogenous doubling agent to induce genome duplication, and transplanted to the field. Following successful self-pollination, seeds harvested from the ear represent fully homozygous lines. The seed set at this stage, however, is often low, necessitating one or two additional rounds of self-pollination to increase the number of fully homozygous inbred lines. Here, we describe a protocol for the generation of maize DH lines using maternal haploid-inducing maize lines. We outline the steps for setting up the donor material, performing induction crosses, selecting haploids based on two different marker alleles, treating seedlings with colchicine to double the genome, transplanting the treated seedlings to the field, and self-pollinating the treated plants.

A Human GSDMD Protein-Derived Cell-Penetrating Peptide Enhances the Antitumor Effects of the Proapoptotic Peptide KLA

Cell-penetrating peptides (CPPs) possess significant potential for the transportation of cell-impermeable biological molecules into tumor cells. However, the nonhuman origins of CPPs can cause cytotoxicity and immunogenicity, limiting their clinical applicability. In this study, using in silico approaches combined with in vitro experiments, we identified and characterized a novel CPP named RYK derived from the human gasdermin D (GSDMD) protein. Compared with the R8 peptide, which served as a positive control, RYK exhibited superior penetration efficiency into A549 and HepG2 cells without inducing cytotoxic effects. Confocal laser scanning microscopy further demonstrated that RYK penetrated the nuclei of tumor cells more rapidly than did the R8 peptide. The subsequent experimental results demonstrated that RYK facilitates the cellular internalization of KLA without modifying its cytotoxic mechanism. To summarize, RYK has emerged as a promising CPP for the efficient delivery of exogenous biological agents into tumor cells.

Infrared neuroglial modulation of spinal locomotor networks

Infrared neural stimulation (INS) emerges as a promising tool for stimulating the nervous system by its high spatial precision and absence of the use of exogenous agents into the tissue, which led to the first successful proof of concept in human brain. While neural networks have been the focal point of INS research, this technique is also non cell type specific as it triggers activity in non electrically excitable cells. Despite increasing interest, there remains to demonstrate well defined simultaneous astrocytic and neuronal signals in response to INS. Using calcium imaging, we show that INS has the capacity to initiate calcium signaling in both astrocytes and neurons simultaneously from the rostral lumbar spinal cord, each exhibiting distinct temporal and amplitude characteristics. Importantly, the mechanism underlying infrared-induced neuronal and astrocytic calcium signaling differ, with neuronal activity relying on sodium channels, whereas induced astrocytic signaling is predominantly influenced by extracellular calcium and TRPV4 channels. Furthermore, our findings demonstrate the frequency shift of neuronal calcium oscillations through infrared stimulation. By deepening our understanding in INS fundamentals, this technique holds great promise for advancing neuroscience, deepening our understanding of pathologies, and potentially paving the way for future clinical applications.

Review on Photoacoustic Monitoring after Drug Delivery: From Label-Free Biomarkers to Pharmacokinetics Agents.

Photoacoustic imaging (PAI) is an emerging noninvasive and label-free method for capturing the vasculature, hemodynamics, and physiological responses following drug delivery. PAI combines the advantages of optical and acoustic imaging to provide high-resolution images with multiparametric information. In recent decades, PAI's abilities have been used to determine reactivity after the administration of various drugs. This study investigates photoacoustic imaging as a label-free method of monitoring drug delivery responses by observing changes in the vascular system and oxygen saturation levels across various biological tissues. In addition, we discuss photoacoustic studies that monitor the biodistribution and pharmacokinetics of exogenous contrast agents, offering contrast-enhanced imaging of diseased regions. Finally, we demonstrate the crucial role of photoacoustic imaging in understanding drug delivery mechanisms and treatment processes.

Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family.

Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of Escherichia coli AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1-8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants.

Pathogenic G6PD variants: Different clinical pictures arise from different missense mutations in the same codon.

G6PD deficiency results from mutations in the X-linked G6PD gene. More than 200 variants are associated with enzyme deficiency: each one of them may either cause predisposition to haemolytic anaemia triggered by exogenous agents (class B variants), or may cause a chronic haemolytic disorder (class A variants). Genotype-phenotype correlations are subtle. We report a rare G6PD variant, discovered in a baby presenting with severe jaundice and haemolytic anaemia since birth: the mutation of this class A variant was found to be p.(Arg454Pro). Two variants affecting the same codon were already known: G6PD Union, p.(Arg454Cys), and G6PD Andalus, p.(Arg454His). Both these class B variants and our class A variant exhibit severe G6PD deficiency. By molecular dynamics simulations, we performed a comparative analysis of the three mutants and of the wild-type G6PD. We found that the tetrameric structure of the enzyme is not perturbed in any of the variants; instead, loss of the positively charged Arg residue causes marked variant-specific rearrangement of hydrogen bonds, and it influences interactions with the substrates G6P and NADP. These findings explain severe deficiency of enzyme activity and may account for p.(Arg454Pro) expressing a more severe clinical phenotype.

Prediction of Cancer Proneness under Influence of X-rays with Four DNA Mutability and/or Three Cellular Proliferation Assays.

All these assays were applied to skin untransformed fibroblasts derived from eight major cancer syndromes characterized by their excess of relative cancer risk (ERR). Significant correlations with ERR were found between hyper-recombination assessed by the plasmid assay and G2/M arrest and described a third-degree polynomial ERR function and a sigmoidal ERR function, respectively. The product of the hyper-recombination rate and capacity of proliferation described a linear ERR function that permits one to better discriminate each cancer syndrome. Hyper-recombination and cell proliferation were found to obey differential equations that better highlight the intrinsic bases of cancer formation. Further investigations to verify their relevance for cancer proneness induced by exogenous agents are in progress.

Natural Plant Materials as a Source of Neuroprotective Peptides.

In many circumstances, some crucial elements of the neuronal defense system fail, slowly leading to neurodegenerative diseases. Activating this natural process by administering exogenous agents to counteract unfavourable changes seems promising. Therefore, looking for neuroprotective therapeutics, we have to focus on compounds that inhibit the primary mechanisms leading to neuronal injuries, e.g., apoptosis, excitotoxicity, oxidative stress, and inflammation. Among many compounds considered neuroprotective agents, protein hydrolysates and peptides derived from natural materials or their synthetic analogues are good candidates. They have several advantages, such as high selectivity and biological activity, a broad range of targets, and high safety profile. This review aims to provide biological activities, the mechanism of action and the functional properties of plant-derived protein hydrolysates and peptides. We focused on their significant role in human health by affecting the nervous system and having neuroprotective and brain-boosting properties, leading to memory and cognitive improving activities. We hope our observation may guide the evaluation of novel peptides with potential neuroprotective effects. Research into neuroprotective peptides may find application in different sectors as ingredients in functional foods or pharmaceuticals to improve human health and prevent diseases.

The impact of long-course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum.

The long-term effects of chemoradiotherapy on human rectum are poorly understood. The aims were to investigate changes in inflammatory status, myenteric neuron numbers/phenotype, neuromuscular functions and prokinetic drug efficacy. Macroscopically normal proximal-to-mid rectum was obtained from 21 patients undergoing surgery for bowel cancer, 98days (range: 63-350) after concurrent capecitabine and pelvic radiotherapy, and 19 patients without chemoradiotherapy. Inflammatory status was measured by H&E, CD45 staining and qPCR. Myenteric neurons were examined by immunohistochemistry. Neuromuscular functions and drug efficacy were studied using exogenous agents and electrical field stimulation (EFS) to activate intrinsic nerves. Inflammation was not detected. Numbers of myenteric ganglia/neurons were unchanged (11.7±2.4 vs. 10.3±2.2 neurons/mm myenteric plexus with/without chemoradiotherapy) as were the numbers of cholinergic/nitrergic neurons. EFS stimulated cholinergic and nitrergic neurons so the contractile response of the muscle was the sum of both but dominated by cholinergic (causing contraction) or less often, nitrergic activity (relaxation), followed, after termination of EFS, by neuronally mediated contraction. Inhibition of nitric oxide synthase (by L-NAME 300μM) more clearly defined EFS-evoked contractions. The 5-HT4 agonist prucalopride 10μM and the cholinesterase inhibitor donepezil 1µM, respectively increased and greatly increased the composite contractile response to EFS (measured as 'area-under-the curve') and the contractions isolated by L-NAME (respectively, by 22±14% and 334±87%; n=11/8). After chemoradiotherapy, nitrergic-mediated muscle relaxations occurred more often during EFS (in 29.8±6.1% preparations vs. 12.6±5.1% without chemoradiotherapy, n=21/18). With L-NAME, the ability of prucalopride to facilitate EFS-evoked contraction was lost and that of donepezil approximately halved (contractions increased by 132±36%; n=8). Several months after chemoradiotherapy, the rectum was not inflamed and myenteric neuron numbers/phenotype unchanged. However, nitrergic activity was increased relative to cholinergic activity, and prokinetic-like drug activity was lost or greatly reduced. Thus, chemoradiotherapy causes long-term changes in neuromuscular functions and markedly reduces the efficacy of drugs for treating constipation.

Unsupervised adversarial neural network for enhancing vasculature in photoacoustic tomography images using optical coherence tomography angiography

Photoacoustic tomography (PAT) is a powerful imaging modality for visualizing tissue physiology and exogenous contrast agents. However, PAT faces challenges in visualizing deep-seated vascular structures due to light scattering, absorption, and reduced signal intensity with depth. Optical coherence tomography angiography (OCTA) offers high-contrast visualization of vasculature networks, yet its imaging depth is limited to a millimeter scale. Herein, we propose OCPA-Net, a novel unsupervised deep learning method that utilizes the rich vascular feature of OCTA to enhance PAT images. Trained on unpaired OCTA and PAT images, OCPA-Net incorporates a vessel-aware attention module to enhance deep-seated vessel details captured from OCTA. It leverages a domain-adversarial loss function to enforce structural consistency and a novel identity invariant loss to mitigate excessive image content generation. We validate the structural fidelity of OCPA-Net on simulation experiments, and then demonstrate its vascular enhancement performance on in vivo imaging experiments of tumor-bearing mice and contrast-enhanced pregnant mice. The results show the promise of our method for comprehensive vessel-related image analysis in preclinical research applications.

NIR-II femtosecond laser-induced nonlinear absorption facilitates foreground-extraction photoacoustic imaging by monolayer WS2-PVP nanosheets

Exogenous contrast agents have been extensively applied in photoacoustic (PA) molecular imaging for disease diagnosis, benefiting from their advantageous optical, thermal, and internal delivery properties. However, their in vivo performance was inevitably interfered by background tissue optical absorption, resulting in low imaging contrast and sensitivity. Here, we report a NIR-II femtosecond laser-induced nonlinearly enhanced PA imaging technique based on two-photon absorption of monolayer WS2-PVP nanosheets (NSs), which facilitates foreground extraction of the targeting region with the background signal being significantly suppressed. The optical nonlinearity of the monolayer WS2-PVP NSs was first demonstrated by a Z-scan system under the irradiation of a femtosecond laser to be 0.38, with an antithesis of virtually zero for the tissue-mimicking sample. Experiments on tissue-mimicking phantoms and in vitro chicken breast showed that the nonlinear PA enhancement of monolayer WS2-PVP NSs can facilitate foreground-extraction imaging at deep-seated position up to 4 mm. In addition, the in vivo foreground-extraction imaging ability by using monolayer WS2-PVP NSs was further demonstrated by mouse tumor models, where the tumor regions were specifically extracted with high imaging contrast. This work proposed a nonlinearly enhanced contrast mechanism of PA nanoprobes, prefiguring great potential for high-contrast and high-specificity PA molecular imaging.

Robust Sequence Design Space for the Isothermal Exponential Amplification of Short Oligonucleotides.

Advances in isothermal amplification techniques have accelerated development in biosensing applications and the design of complex molecular devices. The exponential amplification reaction technique, or EXPAR, is uniquely positioned to process molecular information from short oligonucleotide strands (≈10nucleotides length) typically encountered in molecular computing or microRNA detection. Despite its conceptual simplicity (requiring only a template strand and two enzymes), the issue of nonspecific background amplification has hindered broader adoption. In this work, a new system configuration is established at 37 °C to achieve significantly improved performance. Critical sequence motifs responsible for the excellent signal-to-background profile are identified and generalized as a universal adapter design framework. Orthogonal template sequences generated from the framework are implemented for a triplex reaction and successfully evaluated mixtures of multiple-target inputs in a single-step, one-pot format without the need for exogenous agents.

Mitochondrial DNA damage, repair and copy number dynamics of Sclerophytum sp. (Anthozoa: Octocorallia) in response to short-term abiotic oxidative stress

As a consequence of global climate change, the increasing frequency of environmental disturbances and surplus oxidative stress experienced by coral reefs will likely contribute to phase shifts from stony to soft corals. Mitochondrial response to reactive oxygen species (ROS) -induced oxidative damage appears pivotal for bioenergetic adaptation and recovery during environmental stress, partly governed by mitochondrial DNA copy number. Unlike other animals, octocorals possess unique mitogenomes with an intrinsic DNA mismatch repair gene, the mtMutS, that is likely to have a role in mitochondrial response and mtDNA damage recovery. Yet, there is a general lack of stress response studies on octocorals from a mitochondrial perspective. Here we evaluate the mitochondrial response of the octocoral Sclerophytum sp. subjected to acute elevated temperature and low pH, and its putative competence to reverse oxidative mtDNA damage caused by exogenous agents like hydrogen peroxide (H2O2). Temporal changes in mtDNA copy number and mtDNA damage and recovery were monitored. Both short-term thermal and low pH stress applied independently instigated mtDNA damage and affected mtDNA copy number differently, while mtMutS gene was significantly upregulated during low pH stress. mtDNA damage caused by H2O2 insult was observed to be promptly reversed in Sclerophytum sp., and a higher mtDNA copy number was associated with lower mtDNA damage. These findings provide insights into the potential role of mtMutS gene in conferring resilience to octocorals, the relevance of mtDNA copy number, and emphasize the importance of better understanding the mitochondrial stress response of cnidarians in the context of climate change.

Sharp-peaked lanthanide nanocrystals for near-infrared photoacoustic multiplexed differential imaging

Photoacoustic tomography offers a powerful tool to visualize biologically relevant molecules and understand processes within living systems at high resolution in deep tissue, facilitated by the conversion of incident photons into low-scattering acoustic waves through non-radiative relaxation. Although current endogenous and exogenous photoacoustic contrast agents effectively enable molecular imaging within deep tissues, their broad absorption spectra in the visible to near-infrared (NIR) range limit photoacoustic multiplexed imaging. Here, we exploit the distinct ultrasharp NIR absorption peaks of lanthanides to engineer a series of NIR photoacoustic nanocrystals. This engineering involves precise host and dopant material composition, yielding nanocrystals with sharply peaked photoacoustic absorption spectra (~3.2 nm width) and a ~10-fold enhancement in NIR optical absorption for efficient deep tissue imaging. By combining photoacoustic tomography with these engineered nanocrystals, we demonstrate photoacoustic multiplexed differential imaging with substantially decreased background signals and enhanced precision and contrast.

Clinical Applications of Cardiac Magnetic Resonance Parametric Mapping.

Cardiovascular magnetic resonance (CMR) imaging is widely regarded as the gold-standard technique for myocardial tissue characterization, allowing for the detection of structural abnormalities such as myocardial fatty replacement, myocardial edema, myocardial necrosis, and/or fibrosis. Historically, the identification of abnormal myocardial regions relied on variations in tissue signal intensity, often necessitating the use of exogenous contrast agents. However, over the past two decades, innovative parametric mapping techniques have emerged, enabling the direct quantitative assessment of tissue magnetic resonance (MR) properties on a voxel-by-voxel basis. These mapping techniques offer significant advantages by providing comprehensive and precise information that can be translated into color-coded maps, facilitating the identification of subtle or diffuse myocardial abnormalities. As unlikely conventional methods, these techniques do not require a substantial amount of structurally altered tissue to be visually identifiable as an area of abnormal signal intensity, eliminating the reliance on contrast agents. Moreover, these parametric mapping techniques, such as T1, T2, and T2* mapping, have transitioned from being primarily research tools to becoming valuable assets in the clinical diagnosis and risk stratification of various cardiac disorders. In this review, we aim to elucidate the underlying physical principles of CMR parametric mapping, explore its current clinical applications, address potential pitfalls, and outline future directions for research and development in this field.

Intoxicações de animais por praguicidas da classe dos carbamatos

Intentional poisoning by exogenous agents occurs with certain frequency and represents a high percentage of the causes of death in small animals in Veterinary Medicine. The carbamate popularly known in Brazil as “chumbinho”, is often linked to cases of criminal poisoning of domestic animals in the country, being sold illegally and widely used as a domestic rodenticide. The objective of this work was to discuss some types of pesticides and their toxicities, having inorganic and organic substances in their composition. A systematic review of national and international literature was carried out using the following key words: anticholinesterases, carbamates, pesticides, poisoning; using the following scientific databases for academic research: Virtual Health Library (VHL), SciELO, Scopus, CAPES Journal Portal, Google Scholar, PubMed and Biomed Central. Pesticides, with their inorganic chemical nature, appear in everyday life and are classified as organochlorines, organophosphates, carbamates and others, having an immediate effect in the organism. Cases of poisoning involving toxic agents illegally sold as rodenticides are very frequent and it is noted that, in most cases, the lack of knowledge and/or lack of information on the part of owners regarding the subject are significant factors in cases of sudden death of poisoned animals treated in veterinary clinics. The best way to reduce the incidence of poisoning in companion animals can be through training veterinarians working in the area of first aid, as well as their involvement in prevention through raising awareness among the population regarding the use of these toxic agents. There is also a need for greater supervision of the illegal marketing of these chemicals by public bodies.

Quantitative non-contrast perfusion MRI in the body using arterial spin labeling.

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method that enables the assessment and the quantification of perfusion without the need for an exogenous contrast agent. ASL was originally developed in the early 1990s to measure cerebral blood flow. The utility of ASL has since then broadened to encompass various organ systems, offering insights into physiological and pathological states. In this review article, we present a synopsis of ASL for quantitative non-contrast perfusion MRI, as a contribution to the special issue titled "Quantitative MRI-how to make it work in the body?" The article begins with an introduction to ASL principles, followed by different labeling strategies, such as pulsed, continuous, pseudo-continuous, and velocity-selective approaches, and their role in perfusion quantification. We proceed to address the technical challenges associated with ASL in the body and outline some of the innovative approaches devised to surmount these issues. Subsequently, we summarize potential clinical applications, challenges, and state-of-the-art ASL methods to quantify perfusion in some of the highly perfused organs in the thorax (lungs), abdomen (kidneys, liver, pancreas), and pelvis (placenta) of the human body. The article concludes by discussing future directions for successful translation of quantitative ASL in body imaging.

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury.

Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.

The Antioxidant Potential of Saudi Propolis Extract on Hepatorenal Toxicity in Mice

Background: In advanced cirrhotic conditions, hepatorenal syndrome detrimentally affects renal function. Interest has grown in propolis for its cytoprotective properties against various exogenous agents. This study evaluates the efficacy of Saudi propolis extracts in mitigating hepatorenal toxicity induced by carbon tetrachloride in mice. Methods: Thirty-two male Swiss Albino mice were divided into four groups: a Control (-) group receiving distilled water; a Control (+) group subjected to intraperitoneal CCl4 at 0.5 mL/kg (20% v/v in corn oil) on day 6; a Standard group treated daily with silymarin at 200 mg/kg and a group given an oral dose of aqueous propolis extract (APE) at 8.4 mg/kg. Result: Histological and biochemical analyses confirm propolis extract’s role in preventing hepatocyte apoptosis and reducing inflammatory infiltrates in kidney tissues, improving the histological appearance of hepatic and renal tissues with fewer fibrotic changes. The application of immunohistochemistry, along with reductions in anti-apoptotic proteins such as BCL-2 and p53, supports these findings, highlighting the antioxidant potential of Saudi propolis extracts in addressing hepatorenal toxicity.