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Khalid Alhazzani,1 Hanan Mohammed,1 Mohammad M Algahtani,1 Khaldoon Aljerian,2 Ali Alhoshani,1 Homood M As Sobeai,1 Syed Rizwan Ahamad,3 Moureq R Alotaibi,1 Abdullah S Alhamed,1 Fawaz Alasmari,1 Mohammed Alqinyah,1 Hussain N Alhamami,1 Ahmed Z Alanazi1 1Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 2Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Ahmed Z Alanazi, Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia, Email azalanazi@ksu.edu.saBackground: Dasatinib (DASA) is associated with cardiotoxic effects, posing risks to patients. Valsartan (VAL) may offer protective benefits against these effects. This study evaluates the impact of DASA, VAL, and their combination on cardiac health.Methods: Wistar rats were treated with DASA, VAL, and a combination of VAL and DASA intraperitoneally every other day for 14 days. Body weight and survival rates were monitored. Serum levels of cardiac biomarkers (CPK, LDH, AST) were analyzed. Histopathological and immunohistochemical analyses assessed myocardial architecture and apoptosis-related protein expression. Metabolomic profiling was conducted using GC-MS to identify metabolic changes across treatment groups.Results: The DASA group experienced significant weight loss and a 50% mortality rate, while the combination group had no mortality. Cardiac biomarkers like CPK, LDH, and AST were elevated in the DASA group but significantly reduced in the VAL + DASA group. Histopathological examination showed significant myocardial injury in the DASA group, with improved cardiac tissue morphology in the combination group. Immunohistochemical analysis revealed altered expression of apoptosis-related proteins, including caspase-3 and BCL-2, with improved levels in the combination group compared to DASA alone. Metabolomic profiling identified significant metabolic shifts, with 15 metabolites differentiating the treatment groups, and the VAL + DASA group mitigated the metabolic disturbances caused by DASA.Conclusion: The study suggesting VAL’s potential therapeutic role in managing DASA-induced cardiac toxicity. The combination of VAL with DASA not only improved survival rates and reduced cardiac biomarker levels but also preserved myocardial architecture and normalized metabolic profiles. These findings highlight the importance of integrated approaches in evaluating drug efficacy and suggest VAL as a promising candidate for protecting cardiac function in preclinical models of DASA therapy.Keywords: cardiac toxicity, dasatinib, valsartan, metabolomics, histopathology

Abstract Background Oreochromis niloticus has great economic value and potential for farming and development. Transportation of fish was done for breeding or trading purpose and it is a challenging aspect of aquaculture. This study aimed to investigate the effect of transportation in freshwater and brackish water on the resistance of O. niloticus as well as transportation stress mitigation effect of NaCl. Four equal groups were used; each of 50 fish, the 1st group served as the control (P 1), while the 2nd group (PT 2) was transported in water without salt, the 3rd (PT 3) and 4th (PT 4) groups were transported in water containing 5 gL− 1 and 10 gL− 1 salt respectively. PT 2, PT 3 and PT 4 were transported for 5 h without any rest or sedative drugs. Results The serum cortisol of O. niloticus significantly increased at 0 h and then decreased at 12 and 24 h post transportation in the PT 2 group and non-significantly increased at all point times in the PT 3 and PT 4 groups comparing to P 1 group. Mucin2 gene (MUC2) expression was non-significantly up regulated in the PT 2 group and down regulated in the PT 3 and PT 4 groups at 0 h comparing with P 1 group, but at 12 and 24 h it was significantly up regulated in the PT 2, PT 3 and PT 4 groups. The β Defensin-1 (β D1) and 2 (β D2) genes expression was non-significantly down-regulated in the PT 2 group and significantly up regulated in the PT 3 and PT 4 groups at 0 h., while at 12 and 24 h was significantly down regulated in the PT 2 group and non-significantly down regulated in the PT 3 and PT 4 groups, it significantly down regulated in the PT 2 and PT 3 group and non-significantly down regulated in the PT 4 group at 24 h. Non-significant up regulation in interleukin − 1β (IL-1β) gene expression was reported in the PT 2 group and non-significant down regulation in the PT 3 and PT 4 groups at 0 h. However, significant up regulation was recorded in the PT 2, PT 3 and PT 4 groups at 12 and 24 h. The Tumor necrosis factor-alpha (TNF–α) gene expression was non-significantly up regulated in the PT 2 group and non-significantly down regulated in the PT 3 and PT 4 groups at 0 h. However, it was significantly up regulated in the PT 2, PT 3 and PT 4 groups at 12 and 24 h. Conclusion The results of this study confirmed the stressful effect of transportation on O. niloticus as well as the transportation stress mitigation effect of NaCl.

Introduction: Evolocumab’s short-term efficacy and safety were proven in phase-3 clinical trial, but its long-term safety and effectiveness in the Saudi population are yet to be studied. The aim of this study was to assess the long-term safety and effectiveness of evolocumab in Saudi patients with primary hypercholesterolemia or mixed dyslipidemia. Method: A retrospective cohort study evaluated adult patients who had newly been prescribed evolocumab for hypercholesterolemia or mixed dyslipidemia. Safety events included myocardial infarction, unstable angina, stroke, transient ischemic attack, heart failure, rhabdomyolysis, renal dysfunction, and myalgia. Effectiveness outcomes included changes in lipid profiles from baseline, assessed at 6-, 12-, 18-, and 24-month. Results: The study sample were 469 who newly prescribed evolocumab, from which 69.1 % being male, were included. The most prevalent comorbidities were coronary artery disease, diabetes, and hypertension. Statin was the most commonly used therapy. The most common adverse events at 6-month follow-up, based on the incidence rate per 1000 person-years, were coronary revascularization (63.20), myalgia (44.96), myocardial infarction (31.53), unstable angina (31.49), heart failure (26.94), rhabdomyolysis without renal dysfunction (8.93), transient ischemic attack (4.46), and rhabdomyolysis with renal dysfunction (4.46). Stroke incidence increased with follow-up length, from 8.87 per 1000 person-years at 6 months to 12.84 per 1000 person-years at 24 months. Evolocumab use significantly reduced LDL and total cholesterol levels at 6, 12, 18, and 24 months follow-up, while having no significant effect on HDL or triglycerides levels. Conclusion: Evolocumab appeared to be safe and effective therapeutic option for patients with primary hypercholesterolemia or mixed dyslipidemia to potentially reduce LDL levels to therapeutic levels when statins are insufficient.

As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.

β-Diketones, also known as 1,3-diketones, hold significant importance in synthetic organic chemistry. This review aims to provide a comprehensive overview of the seven different methods used to prepare 1,3-diketones. and these methods have been described by several researchers. In addition, β-Diketone derivatives have unique physical and chemical properties, as they exist in different tautomeric chemical forms. The most prominent derivatives of 1,3-diketones are highlighted, and the focus is on their diverse applications in various fields.

Recent national reports have indicated an increasing trend of dental decay among school-aged children. National school-based data are required to guide decision-making to ensure effective public health efforts to manage dental decay. This study aimed to assess the prevalence of dental decay among school-age children in Saudi Arabia and explore the possible link between dental decay and weight status. This was a cross-sectional analysis of a national sample including 1,134,317 Saudi children in the 1st, 4th, 7th, and 10th grades who participated in a national school screening program. Data for weight, height, body mass index (BMI), dental decay prevalence, and decayed, missing, and filled teeth (DMFT) index were analysed. An independent t-test, one-way analysis of variance, and chi-square test were used to compare the means, while Pearson’s r correlation and multiple linear regression were used to examine the relationships between the study variables. The prevalence of dental decay was 24.20%, and dental decay was the highest among female students (26.5%), students in primary school (25.9%), students living in the eastern region (35.2%), in the administrative capital (27.6%), and in rural areas (23.4%). Dental decay was the highest among students who were underweight. Female sex and living in rural areas significantly predicted higher DMFT while being overweight/obese significantly predicted lower DMFT. Dental decay is highly prevalent among underweight students, female students, and students living in rural areas and the eastern regions of Saudi Arabia. To reduce the prevalence of dental decay and related health disparities, dental health screening programs should be designed to detect dental decay early among children at high risk due to abnormal BMIs and sociodemographic factors. In addition, dental health screening and management programs should utilize standardized dental decay assessment methods and ethnically representative growth charts.

English, as a language, has become a common way of communication across the globe, resulting in a need for many to read and understand the language. As various countries have opened up to foreigners who seek to do business, study, or live in non-English-speaking countries, the need for having a common language has led to the establishment of English across the world. Over the years, non-native English-speaking countries have developed curriculums for their citizens, especially adults to enable them to teach themselves English. However, the courses have been rather expensive to undertake, leaving the underprivileged looking for alternatives. This paper seeks to look into the issue of accessibility by introducing the benefits of technology in learning English as a Second Language (ESL) and discussing how it has revolutionised teaching in non-native speaking countries. More specifically, this paper will look at Computer-Assisted Language Learning (CALL) and its importance towards teaching ESL. Additionally, it will highlight the importance of technology towards teaching students ESL through software and websites, as well as shed light towards some of the negative aspects of technology integration in ESL adult learning.

BackgroundPseudomonas aeruginosa is a common pathogen causing healthcare-associated infections. Most surveillance studies from Saudi Arabia that assessed the resistance by P. aeruginosa were conducted in single centers or did not use broth microdilution (BMD), the gold standard test. This is the first national multicenter study to assess the resistance profiles of P. aeruginosa isolates in Saudi Arabia using BMD.MethodsBetween 2022 and 2023, isolates from various infection sites were collected from seven hospitals in seven different regions of Saudi Arabia. The isolates were shipped to an academic microbiology lab, where their susceptibility was tested by BMD following Clinical Laboratory Standards Institute guidelines using Sensititre GNX3F plates. %Susceptibility to each antibiotic, and MIC50 and MIC90 were determined.ResultsIn total, 185 P. aeruginosa isolates were collected. Most isolates came from respiratory specimens (34.1%), followed by urine (21.1%) and skin/soft tissue (17.8%). The highest susceptibility was to amikacin (76.8%). Concurrently, susceptibility to meropenem was 52%, but it was 43.8% to colistin. While all P. aeruginosa isolates met the definition of multidrug-resistance, 41 (22.2%) were difficult-to-treat and 10 (5.4%) were pandrug-resistant. Difficult-to-treat isolates made up 30.3% of skin and soft tissue isolates, 25.4% of respiratory isolates, 21.7% of blood isolates, and 17.9% of urine isolates.ConclusionPseudomonas aeruginosa demonstrated an unexpectedly high level of resistance to several commonly used antibiotics. Therefore, antimicrobial stewardship and infection control policies should be strictly enforced by hospitals across the country to optimize treatment, prevent the emergence and spread of resistant strains, and track resistance trends with local antibiograms.

BackgroundHalitosis, a socially and psychologically impactful condition often resulting from oral or systemic issues, is exacerbated by factors like aging, poor oral hygiene, and dietary choices. This study aimed to investigate the association between halitosis and stress by measuring salivary cortisol levels and the Cohen's Perceived Stress Scale (CPSS).MethodsA cross-sectional study of 40 participants was conducted using questionnaires and clinical measurements to assess halitosis and stress levels. Saliva samples were collected and analyzed for cortisol using ELISA. Participants’ stress was assessed with the Cohen's Perceived Stress Scale Questionnaire (CPSS-10) questionnaire, and halitosis was measured with a Halimeter and self-assessment questionnaire. Clinical measurements included Plaque Index (PI) and the Decayed, Missing, and Filled Teeth (DMFT) score.ResultsForty subjects were split into a halitosis group (mean age 30.75 ± 10.15) and group with no halitosis (mean age 26 ± 5.3). Objective measures confirmed higher halitosis scores (3.70 ± 0.73) in the halitosis group vs. the second group (2.60 ± 1.67). Compared with the group with no halitosis, the halitosis group exhibited significantly (p

IntroductionBreast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC.MethodsOur objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS.ResultsSixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques.DiscussionThese genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment.

Abstract Background This work aims to develop clinical practice recommendations for the management of systemic sclerosis (SSc). Results Fourteen expert panels had completed the two rounds of surveys. After the end of round 2, recommendations were released and distributed on 11 domains. The percentage of the agreement on the recommendations was 92.3% to 100%. All 11 key questions were answered at the end of the second round with agreement. Conclusion This guideline tried to tackle the gaps in research that limit treatment options. Stratifying the patients according to their disease domains has helped to set up sequential management pathways for each domain.

Abstract Purpose To assess the relationship between the triad of obesity, fracture risk factors, and osteoporosis and its impact on fragility fractures. Results Osteoporosis was least prevalent (p

Cancer is the leading cause of mortality worldwide. In patients with metastatic non-small cell lung cancer, epidermal growth factor receptor (EGFR) is often overexpressed. Gefitinib (GEF), an inhibitor of EGFR, is approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the low solubility and dissolution of GEF limits its bioavailability. Numerous methods, including solid dispersion (SD) and complexation, have been reported to enhance the dissolution of poorly soluble drugs. In this study, GEF complexes were prepared using methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) in two molar ratios (1:1 and 1:2), furthermore, GEF SDs were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188(PXM) in three different ratios (1:2, 1:4 and 1:6 w/w). Dissolution studies were conducted on the prepared formulations. Dissolution results showed a 1.22–2.17-fold enhancement in drug dissolution after one hour compared to untreated GEF. Two formulations that showed higher dissolution enhancement were subsequently evaluated for in-vitro cytotoxicity and were formulated into tablets. The selected PVP–GEF (1:4 w/w) and MβCD–GEF (1:1M) formulas displayed improved cytotoxicity compared to untreated GEF. The IC50 values of the PVP–GEF and MβCD–GEF were 4.33 ± 0.66 and 4.84 ± 0.38 µM, respectively which are significantly lower (p

Abstract Purpose (1) This was a multi-center, cross-sectional, observational study. Both old men and postmenopausal women over 50 years old who were admitted with an osteoporotic fracture (whether hip fracture or major osteoporosis) were consecutively recruited for this work and managed under the Fracture Liaison Service. All the patients were assessed for their sarcopenia risk (SARC-F), fracture risk (FRAX), and fall risk (FRAS) as well as functional disability (HAQ). The aim was to assess the prevalence of sarcopenia risk among older adult Egyptians presenting with fragility fractures. (2) To identify the relation between sarcopenia risk with the risk of falling as well as sustaining a fragility fracture. Results Two hundred and thirty-six patients (69 males, 167 females) were included in this work. The mean age was 70.1 (SD = 9.2) years. The prevalence of sarcopenia was 69.7%. The sarcopenia risk score was positively correlated with the FRAX score (p = 0.01). The prevalence of high sarcopenia risk was 78% of the patients presenting with a high 10-year probability of major osteoporosis fracture as well as a 10-year probability of hip fracture. The sarcopenia risk score was positively correlated with the increased fall risk (p = 0.01) as scored by the FRAS scale. There was a significant relation (p

Abstract Mini abstract This work studies the direct cost of hip fractures in Egypt. The direct cost was calculated based on the incidence of hip fracture in Egypt retrieved from the national database. The result of this work raises red flags to the policy makers in Egypt that such fragility fractures are preventable, should appropriate approaches be implemented. Background This study provides an analysis for the healthcare system in Egypt. It was carried out to assess the direct annual cost incurred to the Egyptian healthcare system in 2023 as a result of fragility hip fractures in older adult Egyptians. Results The direct costs of hip fractures incurred during the first year after the injury were estimated at 1,969,385,000 Egyptian pounds (US $63,734,142.4). Time from fracture to surgery was 2.2 + 0.5 days. The average hospital stay after hip fracture surgery was 5.2 + 2.6 days. 4.5% of patients died after surgery, on average 2.3 + 0.4 months. After being discharged from the hospital, all patients needed home care. Conclusion Hip fractures have a significant clinical and financial impact on patients and the healthcare system. This study raises red flags for the healthcare policy makers in Egypt, as the financial burden due to the direct costs of hip fractures justifies extensive prevention programs for osteoporosis and fragility fractures. There is an urgent need to implement diagnostic approaches and validated management protocols for bone health disorders and its associated fractures in Egypt.

Abstract Background Transition of care means the process of educating and empowering adolescents and young adults to take an active role in their own healthcare, develop decision-making skills, and eventually transition from paediatric to adult healthcare providers. Most people do not switch doctors until they are young adults, but it can be beneficial to start preparing children earlier. We aimed to develop a specific toolkit tailored to paediatric and adult rheumatologists to assist them in transitioning of care of young people with juvenile onset rheumatic musculoskeletal diseases from the paediatric to adult rheumatology care. Results The expert panel was confined to an online survey (n = 18), all the experts completed the two rounds. At the conclusion of round 2, a total of 10 points were gathered. The range of respondents (ranks 7–9) who agreed with the recommendations was 88.9 to 100%. All 10 clinical standards identified by the scientific committee were written in the same way. Based on the answers to the structured key questions and the literature review, a structured template was developed presenting transition of care integrated pathway. Conclusion The developed rheumatology-specific guideline offers adolescents and young adults a focussed, multidisciplinary transition of care approach with equity of access, quality of care and flexibility and set up standards for transitional care for young adults with juvenile rheumatological diseases.

Colorectal cancer remains a challenging medical issue worldwide, and utilizing natural products and plants to produce novel, effective and safe therapies against this disease is continuously a sought-after strategy. Fruit and leaf extracts of Pithecellobium dulce (P. dulce) showed potential anticancer properties as they induced apoptosis of breast cancer and Dalton’s lymphoma ascites cells. Thus, the main objective of the current study is to determine whether the seed extract of P. dulce will affect apoptosis, cell cycle, migration, and inflammation of LoVo colorectal cancer cells. The high-resolution liquid chromatography–mass spectrometry was used to determine the chemical composition of the P. dulce seed extract, which revealed the presence of 35 phytochemicals. The findings of this study indicated a significant cytotoxic effect of seeds of this plant in colorectal cancer characterized by induction of apoptosis, cell cycle arrest, and reduction of migration. In addition, the seed extract suppressed several genes that are essential for cancer progression such as MMP2, MMP9, and IL-8, and, on the other hand, upregulated pro-apoptotic genes such as BAX and P53. This study has established P. dulce as a potential and valuable source for providing future therapies against colorectal cancer and other cancers.

Lipopolysaccharides (LPS), the lipid component of gram-negative bacterial cell wall, is recognized as the key factor in acute lung inflammation and is found to exhibit severe immunologic reactions. Phosphodiesterase-4 (PDE-4) inhibitor: “apremilast (AP)” is an immune suppressant and anti-inflammatory drug which introduced to treat psoriatic arthritis. The contemporary experiment designed to study the protective influences of AP against LPS induced lung injury in rodents. Twenty-four (24) male experimental Wistar rats selected, acclimatized, and administered with normal saline, LPS, or AP + LPS respectively from 1 to 4 groups. The lung tissues were evaluated for biochemical parameters (MPO), Enzyme Linked Immunosorbent Assay (ELISA), flowcytometry assay, gene expressions, proteins expression and histopathological examination. AP ameliorates the lung injuries by attenuating immunomodulation and inflammation. LPS exposure upregulated IL-6, TNF-α, and MPO while downregulating IL-4 which were restored in AP pretreated rats. The changes in immunomodulation markers by LPS were reduced by AP treatment. Furthermore, results from the qPCR analysis represented an upregulation in IL-1β, MPO, TNF-α, and p38 whereas downregulated in IL-10 and p53 gene expressions in disease control animals while AP pretreated rats exhibited significant reversal in these expressions. Western blot analysis suggested an upregulation of MCP-1, and NOS-2, whereas HO-1, and Nrf-2 expression were suppressed in LPS exposed animals, while pretreatment with AP showed down regulation in the expression MCP-1, NOS-2, and upregulation of HO-1, and Nrf-2 expression of the mentioned intracellular proteins. Histological studies further affirmed the toxic influences of LPS on the pulmonary tissues. It is concluded that, LPS exposure causes pulmonary toxicities via up regulation of oxidative stress, inflammatory cytokines and stimulation of IL-1β, MPO, TNF-α, p38, MCP-1, and NOS-2 while downregulation of IL-4, IL-10, p53, HO-1, and Nrf-2 at different expression level. Pretreatment with AP controlled the toxic influences of LPS by modulating these signaling pathways.

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.