Death Process Research Articles

M6A modification of lipoyltransferase 1 inhibits bladder cancer progression by activating cuproptosis.

Cuproptosis, a cell death process caused by copper ions, is mediated by protein lipidation related to lipoic acid metabolism. There is a close connection between cuproptosis and the progression and prognosis of various tumors. Here, we identified lipoyltransferase 1 (LIPT1), a key gene related to cuproptosis, was downregulated in bladder cancer (BLCA) and was associated with unfavorable patient prognosis. Restoring the LIPT1 expression in BLCA cells suppressed the proliferation and promoted cuproptosis. Moreover, the consequences of RNA sequencing and Bodipy staining showed that the metabolic pathway mediated by LIPT1 inhibited the accumulation of lipid droplets in cells, disrupted endoplasmic reticulum (ER) homeostasis, and promoted cell apoptosis. Additionally, overexpression of LIPT1 not only repressed the proliferation rate of BLCA cells in vitro but also in vivo. Mechanistically, YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) promoted the degradation of LIPT1 mRNA in a m6A-dependent manner. In summary, these conclusions reveal that LIPT1 promotes cuprotosis and ER stress to inhibit the progression of BLCA, indicating that LIPT1 will provide a powerful treatment direction and drug target for treating BLCA.

Synergistic induction of ferroptosis by targeting HERC1-NCOA4 axis to enhance the photodynamic sensitivity of osteosarcoma

Over the past 30 years, the survival rate for osteosarcoma (OS) has remained stagnant, indicating persistent challenges in diagnosis and treatment. Photodynamic therapy (PDT) has emerged as a novel and promising treatment modality for OS. Despite apoptosis being the primary mechanism attributed to PDT, it fails to overcome issues such as low efficacy and resistance. Ferroptosis, a Fe2+-dependent cell death process, has the potential to enhance PDT's efficacy by increasing reactive oxygen species (ROS) through the Fenton reaction. In this study, we investigated the anti-tumor mechanism of PDT and introduced an innovative therapeutic strategy that synergistically induces apoptosis and ferroptosis. Furthermore, we have identified HERC1 as a pivotal protein involved in the ubiquitination and degradation of NCOA4, while also uncovering a potential regulatory factor involving NRF2. Ultimately, by targeting the HERC1-NCOA4 axis during PDT, we successfully achieved full activation of ferroptosis, which significantly enhanced the anti-tumor efficacy of PDT. In conclusion, these findings provide new theoretical evidence for further characterizing mechanism of PDT and offer new molecular targets for the treatment of OS.

Embracing Endings: Unveiling the Connection Between Final Conversations, the Opportunity Model for Presence, and Coping With the Death of Our Parents.

This study examines adult children's loss of a parent through final conversations and communal coping. By looking at survivors' experiences through the lens of the opportunity model for presence (OMP) during the end-of-life (EOL) process, a model that provides a path of engagement leading to a good or bad death and consequent bereavement processes, we quantitatively test the relationships between two communication constructs before and after death of a parent. While final conversations as one construct did not lead to appraisal or action coping, results illustrate that final conversation topics of identity, instrumental, love, and everyday talk, were significantly related to shared appraisal. Instrumental talk and love were significantly related to joint action. Joint action and shared appraisal together led to participants engaging in all three types of coping. Final conversations as a whole, was important for bereavement outcomes, whereas communal coping's role in these relationships was convoluted.

A computational approach to extreme values and related hitting probabilities in level-dependent quasi-birth–death processes

This paper analyzes the dynamics of a level-dependent quasi-birth–death process X={(I(t),J(t)):t≥0}, i.e., a bi-variate Markov chain defined on the countable state space ∪i=0∞l(i) with l(i)={(i,j):j∈{0,…,Mi}}, for integers Mi∈N0 and i∈N0, which has the special property that its q-matrix has a block-tridiagonal form. Under the assumption that the first passage to the subset l(0) occurs in a finite time with certainty, we characterize the probability law of (τmax,Imax,J(τmax)), where Imax is the running maximum level attained by process X before its first visit to states in l(0), τmax is the first time that the level process {I(t):t≥0} reaches the running maximum Imax, and J(τmax) is the phase at time τmax. Our methods rely on the use of restricted Laplace–Stieltjes transforms of τmax on the set of sample paths {Imax=i,J(τmax)=j}, and related processes under taboo of certain subsets of states. The utility of the resulting computational algorithms is demonstrated in two epidemic models: the SIS model for horizontally and vertically transmitted diseases; and the SIR model with constant population size.

The different paradigms of NK cell death in patients with severe trauma

Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.

Optimized Bionic Drug-Delivery-Inducing Immunogenic Cell Death and cGAS-STING Pathway Activation for Enhanced Photodynamic-Chemotherapy-Driven Immunotherapy in Prostate Cancer.

Prostate cancer presents as a challenging disease, as it is often characterized as an immunologically "cold" tumor, leading to suboptimal outcomes with current immunotherapeutic approaches in clinical settings. Photodynamic therapy (PDT) harnesses reactive oxygen species generated by photosensitizers (PSs) to disrupt the intracellular redox equilibrium. This process induces DNA damage in both the mitochondria and nucleus, activating the process of immunogenic cell death (ICD) and the cGAS-STING pathway. Ultimately, this cascade of events leads to the initiation of antitumor immune responses. Nevertheless, existing PSs face challenges, including suboptimal tumor targeting, aggregation-induced quenching, and insufficient oxygen levels in the tumor regions. To this end, a versatile bionic nanoplatform has been designed for the simultaneous delivery of the aggregation-induced emission PS TPAQ-Py-PF6 and paclitaxel (PTX). The cell membrane camouflage of the nanoplatform leads to its remarkable abilities in tumor targeting and cellular internalization. Upon laser irradiation, the utilization of TPAQ-Py-PF6 in conjunction with PTX showcases a notable and enhanced synergistic antitumor impact. Additionally, the nanoplatform has the capability of initiating the cGAS-STING pathway, leading to the generation of cytokines. The presence of damage-associated molecular patterns induced by ICD collaborates with these aforementioned cytokines lead to the recruitment and facilitation of dendritic cell maturation. Consequently, this elicits a systemic immune response against tumors. In summary, this promising strategy highlights the use of a multifunctional biomimetic nanoplatform, combining chemotherapy, PDT, and immunotherapy to enhance the effectiveness of antitumor treatment.

Repositioning fluphenazine as a cuproptosis-dependent anti-breast cancer drug candidate based on TCGA database

Breast cancer is one of the most prevalent malignancies among women. Enhancing the prognosis is an effective approach to enhance the survival rate of breast cancer. Cuproptosis, a copper-dependent programmed cell death process, has been associated with patient prognosis. Inducing cuproptosis is a promising approach for therapy. However, there is currently no anti-breast cancer drug that induces cuproptosis. In this study, we repositioned the clinical drug fluphenazine as a potential agent for breast cancer treatment by inducing cuproptosis. Firstly, we utilized the Cancer Genome Atlas (TCGA) database and Connectivity Map (CMap) database to identify 22 potential compounds with anti-breast cancer activity through inducing cuproptosis. Subsequently, our findings demonstrated that fluphenazine effectively suppressed the viability of MCF-7 cells. Fluphenazine also significantly inhibited the viability of triple negative breast cancer cells MDA-MB-453 and MDA-MB-231. Furthermore, our study revealed that fluphenazine significantly down-regulated the expression of potential prognostic biomarkers associated with cuproptosis, increased copper ion levels, and reduced intracellular pyruvate accumulation. Additionally, it up-regulated the expression of FDX1 at both the mRNA and protein levels, which has been reported to play a crucial role in the induction of cuproptosis. These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

Research Progress on the Mechanism of Histone Deacetylases in Ferroptosis of Glioma.

Glioma is the most prevalent primary malignant tumor of the central nervous system. While traditional treatment modalities such as surgical resection, radiotherapy, and chemotherapy have made significant advancements in glioma treatment, the prognosis for glioma patients remains often unsatisfactory. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioma and is considered to be the most functionally rich programmed cell death process. Histone deacetylases have emerged as a key focus in regulating ferroptosis in glioma. By inhibiting the activity of histone deacetylases, histone deacetylase inhibitors elevate acetylation levels of both histones and non-histone proteins, thereby influencing various cellular processes. Numerous studies have demonstrated that histone deacetylases are implicated in the development of glioma and hold promise for its treatment. This article provides an overview of research progress on the mechanism by which histone deacetylases contribute to ferroptosis in glioma.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid β proteotoxicity.

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals. However, the degree to which iron overload contributes to AD pathogenesis is unclear. Here, we evaluated the involvement of ferroptosis, an iron-dependent cell death process, in mediating AD-like pathologies in C. elegans. Results showed that iron accumulation occurred prior to the loss of neuronal function as worms age. In addition, energetic imbalance was an early event in iron-induced loss of neuronal function. Furthermore, the loss of neuronal function was, in part, due to increased mitochondrial reactive oxygen species mediated oxidative damage, ultimately resulting in ferroptotic cell death. The mitochondrial redox environment and ferroptosis were modulated by pharmacologic processes that exacerbate or abolish iron accumulation both in wild-type worms and worms with increased levels of neuronal amyloid beta (Aβ). However, neuronal Aβ worms were more sensitive to ferroptosis-mediated neuronal loss, and this increased toxicity was ameliorated by limiting the uptake of ferrous iron through knockout of divalent metal transporter 1 (DMT1). In addition, DMT1 knockout completely suppressed phenotypic measures of Aβ toxicity with age. Overall, our findings suggest that iron-induced ferroptosis alters the mitochondrial redox environment to drive oxidative damage when neuronal Aβ is overexpressed. DMT1 knockout abolishes neuronal Aβ-associated pathologies by reducing neuronal iron uptake.

Ray–Knight compactification of birth and death processes

A birth and death process is a continuous-time Markov chain with minimal state space N, whose transition matrix is standard and whose density matrix is a birth–death matrix. Birth and death process is unique if and only if ∞ is an entrance or natural. When ∞ is neither an entrance nor natural, there are two ways in the literature to obtain all birth and death processes. The first one is an analytic treatment proposed by Feller in 1959, and the second one is a probabilistic construction completed by Wang in 1958.In this paper we will give another way to study birth and death processes using the Ray–Knight compactification. This way has the advantage of both the analytic and probabilistic treatments above. By applying the Ray–Knight compactification, every birth and death process can be modified into a càdlàg Ray process on N∪{∞}∪{∂}, which is either a Doob processes or a Feller Q-process. Every birth and death process in the second class has a modification that is a Feller process on N∪{∞}∪{∂}. We will derive the expression of its infinitesimal generator, which explains its boundary behaviours at ∞. Furthermore, by using the killing transform and the Ikeda–Nagasawa–Watanabe piecing out procedure, we will also provide a probabilistic construction for birth and death processes. This construction relies on a triple determining the resolvent matrix introduced by Wang and Yang in their work (Wang and Yang, 1992).

A Bertalanffy–Richards growth model perturbed by a time-dependent pattern, statistical analysis and applications

We analyze a modification of the Richards growth model by introducing a time-dependent perturbation in the growth rate. This modification becomes effective at a special switching time, which represents the first-crossing-time of the Richards growth curve through a given constant boundary. The relevant features of the modified growth model are studied and compared with those of the original one. A sensitivity analysis on the switching time is also performed. Then, we define two different stochastic processes, i.e. a non-homogeneous linear birth–death process and a lognormal diffusion process, such that their means identify to the growth curve under investigation. For the diffusion process, we address the problem of parameters estimation through the maximum likelihood method. The estimates are obtained via meta-heuristic algorithms (namely, Simulated Annealing and Ant Lion Optimizer). A simulation study to validate the estimation procedure is also presented, together with a real application to oil production in France. Special attention is devoted to the approximation of switching time density, viewed as the first-passage-time density for the lognormal process.

Information Dynamics in Evolving Networks Based on the Birth-Death Process: Random Drift and Natural Selection Perspective

Information Dynamics in Evolving Networks Based on the Birth-Death Process: Random Drift and Natural Selection Perspective

FASTKD1 as a diagnostic and prognostic biomarker for STAD: Insights into m6A modification and immune infiltration.

Fas-activated serine/threonine kinase domain 1 (FASTKD1), a known modulator of mitochondrial-mediated cell death and survival processes, has garnered attention for its potential role in various biological contexts. However, its involvement in gastric cancer remains unclear. Thus, the present study aimed to investigate the relationship between FASTKD1 expression and key factors, including clinicopathological characteristics, immune infiltration and m6A modification in stomach adenocarcinoma (STAD). The expression of FASTKD1 was analyzed in STAD and normal adjacent tissues to assess its association with clinicopathological characteristics and survival prognosis. Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study. Additionally, the findings were validated through immunohistochemical staining. Co-expression analysis of FASTKD1 was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and LinkedOmics database analysis. An in-depth analysis was conducted using databases, such as Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GEO and TCGA to explore the potential correlation between FASTKD1 expression and immune infiltration and m6A modification in STAD. The results revealed that FASTKD1 was significantly upregulated across different tumor types, including STAD. Notably, FASTKD1 was able to distinguish between tumor and normal tissue samples with accuracy. Furthermore, the expression levels of FASTKD1 were significantly associated with clinical stage and survival. Through GO/KEGG enrichment analysis and GSEA, it was revealed that the genes co-expressed with FASTKD1 were active in a variety of biological processes. Within the TIMER, GEPIA and TCGA databases, a notable inverse correlation was observed between FASTKD1 expression and the abundance of immune cell subsets. Notably, significant correlations were established between FASTKD1 and m6A modification genes, YTHDF1 and LRPPRC, in both TCGA and GEO datasets. In conclusion, FASTKD1 may serve a significant role in m6A modification and immune infiltration processes, making it a potentially valuable diagnostic and prognostic biomarker in STAD.

A macroevolutionary analysis of European Late Upper Palaeolithic stone tool shape using a Bayesian phylodynamic framework.

Phylogenetic models are commonly used in palaeobiology to study the patterns and processes of organismal evolution. In the human sciences, phylogenetic methods have been deployed for reconstructing ancestor-descendant relationships using linguistic and material culture data. Within evolutionary archaeology specifically, phylogenetic analyses based on maximum parsimony and discrete traits dominate, which sets limitations for the downstream role cultural phylogenies, once derived, can play in more elaborate analytical pipelines. Recent methodological advances in Bayesian phylogenetics, however, now allow us to infer evolutionary dynamics using continuous characters. Capitalizing on these developments, we here present an exploratory analysis of cultural macroevolution of projectile point shape evolution in the European Final Palaeolithic and earliest Mesolithic (approx. 15 000-11 000 BP) using a Bayesian phylodynamic approach and the fossilized birth-death process model. This model-based approach leaps far beyond the application of parsimony, in that it not only produces a tree, but also divergence times, and diversification rates while incorporating uncertainties. This allows us to compare rates to the pronounced climatic changes that occurred during our time frame. While common in cultural evolutionary analyses of language, the extension of Bayesian phylodynamic models to archaeology arguably represents a major methodological breakthrough.

HSP90/LSD1 dual inhibitors against prostate cancer as well as patient-derived colorectal organoids

The rational installation of pharmacophores targeting HSP90 and LSD1 axes has achieved significant anti-cancer capacity in prostate and colorectal cancer. Among the series of hybrids, inhibitor 6 exhibited remarkable anti-proliferative activity against prostate cancer cell lines PC-3 and DU145, with GI50 values of 0.24 and 0.30 μM, respectively. It demonstrated notable efficacy in combinatorial attack and cell death initiation towards apoptosis. The cell death process was mediated by PARP induction and γH2AX signaling, and was also characterized as caspase-dependent and Bcl-xL/Bax-independent. Notably, no difference in eye size or morphology was observed in the zebrafish treated with compound 6 compared to the reference group (AUY922). The profound treatment response in docetaxel-resistant PC-3 cells highlighted the dual inhibitory ability in improving docetaxel sensitivity. Additionally, at a minimum concentration of 1.25 μM, compound 6 effectively inhibited the growth of patient-derived colorectal cancer (CRC) organoids for up to 10 days in vitro. Together, the designed HSP90/LSD1 inhibitors present a novel route and significant clinical value for anti-cancer drug therapy.

Unveiling the mechanism of hesperidin-induced LdTopI-mediated cell death pathway in protozoan parasite Leishmania donovani

Unicellular protozoan parasite Leishmania donovani is the causative agent for visceral leishmaniasis (VL) or Kala-azar, a neglected fatal parasitic disease. The conventional treatment of VL consists of therapeutic agents having several shortcomings such as toxicity, high cost, efficacy variance and increased drug resistance. Therefore, there is a desperate need to develop an effective treatment against the parasite. Previous reports suggested that flavonoids can inhibit the enzyme Leishmania donovani DNA topoisomerase I (LdTopILS). Therefore, for the first time in this present study, we divulge HSP (one of the natural sources of flavonoids), as a potent natural antileishmanial compound with efficacy in BALB/c mice at 20 mg/kg of body weight, inhibits LdTopILS at 97 % of its activity at 160 μM in preincubation condition (competitively). It binds with free enzyme and does not allow it to bind with the substrate DNA. Moreover, HSP does not stabilize DNA-topoisomerase I cleavable complex. Thus, HSP acts a catalytic topoisomerase I inhibitor, which inhibits complete activity by binding with Lys269 and Thr411 of large subunit of the enzyme. On the other hand, HSP induces the topo I-mediated programmed cell death process by the formation of cellular reactive oxygen species, resulting in depolarization of mitochondrial membrane potential, followed by fragmentation of nuclear DNA. Therefore, the present study illuminates a natural flavonoid that in future might be a promising lead for the treatment of VL.

Unlocking Secrets: Lipid Metabolism and Lipid Droplet Crucial Roles in SARS-CoV-2 Infection and the Immune Response.

Lipid droplets (LD) are crucial for maintaining lipid and energy homeostasis within cells. LDs are highly dynamic organelles that present a phospholipid monolayer rich in neutral lipids. Additionally, LDs are associated with structural and non-structural proteins, rapidly mobilizing lipids for various biological processes. Lipids play a pivotal role during viral infection, participating during viral membrane fusion, viral replication, and assembly, endocytosis, and exocytosis. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection often induces LD accumulation, which is used as a source of energy for the replicative process. These findings suggest that LDs are a hallmark of viral infection, including SARS-CoV-2 infection. Moreover, LD participates in the inflammatory process and cell signaling, activating pathways related to innate immunity and cell death. Accumulating evidence demonstrates that LD induction by SARS-CoV-2 is a highly coordinated process, aiding replication and evading the immune system, and may contribute to the different cell death process observed in various studies. Nevertheless, recent research in the field of LDs suggests these organelles according to the pathogen and infection conditions may also play roles in immune and inflammatory responses, protecting the host against viral infection. Understanding how SARS-CoV-2 influences LD biogenesis is crucial for developing novel drugs or repurposing existing ones. By targeting host lipid metabolic pathways exploited by the virus, it is possible to impact viral replication and inflammatory responses. This review seeks to discuss and analyze the role of LDs during SARS-CoV-2 infection, specifically emphasizing their involvement in viral replication and the inflammatory response.

Biochemical analysis of catecholamine and cortisol for the evaluation of the fetal distress in third trimester stillbirths

BackgroundStress hormones like catecholamine and cortisol are thought to reflect the magnitude of physical stress in adults and were studied in relationship to the cause of death and agony time. Intrauterine distress, intrapartum events, and modes of delivery can affect the fetal endocrine stress response, as reflected by biochemical analyses. The aim of the present study was to evaluate the role of catecholamines and cortisol as markers of ante-mortem fetal distress. The role of cortisol as a marker of circadian timing of delivery was also assessed.MethodsA 2-year prospective cohort-comparison inclusion of stillbirths and newborns took place with collection of antemortem data, labor parameters, neonatal outcome, post-mortem data and blood samples. Stillbirths were classified as acute or chronic on the basis of a multidisciplinary evaluation. Heart blood of stillbirths and cord blood of newborns were analyzed by high pressure liquid chromatography (HPLC) for adrenaline and noradrenaline and by immunoassay for cortisol determination.ResultsFifteen stillbirths and 46 newborns, as a comparison group, delivered by spontaneous vaginal birth, elective, and emergency cesarean sections were included. Stillbirths’ main cause of death was cord thrombosis. Levels of adrenaline and noradrenaline (median: 14,188 pg/ml and 230.5 pg/ml, respectively) were significantly higher (p < 0.001) in stillbirths than in newborns and were also higher in acute compared to chronic distress. Cortisol levels were significantly higher (p < 0.05) in spontaneous vaginal delivery (median: 18.2 μg/dl) compared to elective cesarean sections (median: 3.8 μg/dl). No difference in cortisol concentrations was detected between newborns delivered at morning and at afternoon/evening.ConclusionOur results suggest that the biochemical measurement of adrenaline and noradrenaline levels might reflect a marked physical stress response during the process of death in stillbirths. On the contrary, the elevation of cortisol levels could mirror the elevation in maternal cortisol level during vaginal delivery. For the post-mortem evaluation of stillbirths, the analysis of CA levels could provide additional data on the duration of distress, useful to integrate the forensic diagnosis.

Understanding the Multifaceted Process of Aging: Theories, Mechanisms, and Implications for Treatment

The aging process is a multifaceted biological phenomenon characterized by alterations at the molecular, cellular, and organ levels that culminate in a gradual, unavoidable, and unavoidable reduction in the body's capacity to react suitably to internal and/or external stimuli. Aging is a complex process that involves different mechanisms as The "Wear and Tear" Theory ,The Genetic Control Theory ,The Neuroendocrine Theory ,Waste Accumulation Theory ,Divisions Theory, Autoimmune Theory, Thymic-Stimulating Theory ,Mitochondrial Theory Mitochondria, Errors and Repairs Theory, Redundant DNA Theory Cross-Linkage Theory , Death Hormone Theory (DECO), Caloric Restriction Theory ,The Rate of Living Theory ,Gene Mutation Theory, Accumulated mutations Theory, Theory, Order to Disorder Theory, Disposable soma Theory, Antagonistic pleiotropy theory, The Telomerase Theory ,The free radical Theory. The two main categories of aging theories that explain cellular aging are structural damage and programmed theories. Different types of cells experience physiological stressors due to a range of circumstances. Notably, post-mitotic and mitotic cells have different capacities for proliferation and age differently in response to these pressures through different processes of cellular senescence and death, respectively. Over time, these aging cells build up and eventually cause old tissues to malfunction. The aim of this review is to throw light upon the effected of aging and who to treatment it.

Neuroprotective effect of cinnamic alcohol: A bioactive compound of Cinnamomum spp. essential oil

Cinnamic alcohol (CA) is a phenylpropanoid found in the essential oil of the bark of the genus Cinnamomum spp. Schaeff. (Lauraceae Juss.), known as cinnamon. To evaluate the neuroprotective effect of CA and its possible mechanism of action on mice submitted to the pentylenetetrazole (PTZ) induced epileptic seizures model. Behavioral, neurochemical, histomorphometric and immunohistochemistry analysis were carried out. The administration of CA (50–200 mg/kg, i.p., 30 min prior to PTZ and 0.7–25 mg/kg, i.p., 60 min prior to PTZ) increased the latency to seizure onset and the latency to death. The effects observed with CA treatment at 60 min were partially reversed by pretreatment with flumazenil. Furthermore, neurochemical assays indicated that CA reduced the concentration of malondialdehyde and nitrite, while increasing the concentration of reduced glutathione. Finally, histomorphometric and immunohistochemistry analysis revealed a reduction in inflammation and an increase in neuronal preservation in the hippocampi of CA pre-treated mice. Taken together, the results suggest that CA seems to modulate the GABAA receptor, decrease oxidative stress, mitigate neuroinflammation, and reduce cell death processes.