Autism spectrum disorder (ASD) arises from interactions between genetic predisposition and prenatal environmental insults. Prostaglandin E2 (PGE2), derived from cyclooxygenase-2 (COX-2), regulates neuronal differentiation and glia-neuron signaling; thus, its inhibition during gestation may impair neurodevelopment. To examine whether prenatal exposure to indomethacin, a non-selective COX inhibitor, induces autism-like alterations in rats with possible sex differences. Sixteen pregnant Wistar rats received indomethacin (1 mg/kg, gavage) on Gestational Days 10-14. Adult offspring (P50-P54) underwent behavioral tests (open-field, rearing, rotarod, and three-chamber sociability). Hippocampal and cerebellar tissues were analyzed for PGE2, LC3B (ELISA), MDA (TBARS), neuronal density, and GFAP expression (CA1, CA3 - Nissl, GFAP staining). Indomethacin reduced sociability, exploration, and motor performance, especially in males, and decreased PGE2 and LC3B while increasing MDA (p < 0.001). Histologically, CA1 neuronal counts increased while GFAP immunoreactivity was markedly elevated in hippocampal (CA1 and CA3) and cerebellar regions (p < 0.05), reflecting astroglial activation and neuroinflammatory remodeling. Prenatal inhibition of prostaglandin synthesis may disturb PGE2 signaling, leading to oxidative stress, altered autophagy-related signaling, and glial activation, which together contribute to ASD-relevant behavioral outcomes.

Background and Objectives: Sepsis-associated acute kidney injury (SA-AKI) is driven by exaggerated inflammation and oxidative stress, with the HMGB1–RAGE axis playing a pivotal role in amplifying tissue damage. This study aimed to investigate the renoprotective effects of papaverine in a feces-induced peritonitis (FIP) model of sepsis and to explore its impact on HMGB1–RAGE-mediated inflammatory and oxidative pathways. Materials and Methods: Sepsis was induced in male Wistar rats by intraperitoneal injection of fecal slurry (1 g/kg). Animals were treated with papaverine (20 or 40 mg/kg, i.p.) one hour after FIP induction and evaluated at 24 h. Renal function (BUN, creatinine, lactate), inflammatory markers (HMGB1, TNF-α, CRP), oxidative stress (MDA), circulating sRAGE levels, renal NF-κB levels, and histopathological injury scores were assessed. Results: The FIP model resulted in an early mortality rate of 20% and produced marked renal histopathological alterations. Biochemically, FIP increased plasma HMGB1, TNF-α, CRP, MDA, BUN, creatinine, and lactate levels while decreasing sRAGE. Papaverine treatment dose-dependently reduced inflammatory and oxidative markers, restored sRAGE levels, improved renal function parameters, and attenuated histopathological injury. In addition, renal NF-κB levels were significantly elevated in the FIP group compared to controls and were dose-dependently reduced following papaverine treatment. Conclusions: FIP-induced sepsis activates an HMGB1-driven inflammatory–oxidative cascade contributing to SA-AKI. Papaverine confers dose-dependent renoprotection by suppressing HMGB1–RAGE signaling, attenuating NF-κB activation, reducing oxidative stress, and preserving renal structure and function. Targeting the HMGB1–sRAGE axis may represent a promising therapeutic strategy in sepsis-associated renal injury.

Methotrexate (MTX) is a commonly used drug to treat various cancers and autoimmune disorders, but its clinical utility is often limited by hepatotoxicity. β-sitosterol is a bioactive phytosterol compound that is naturally present in various plant foods and exhibits multiple antioxidant, anticancer and immunomodulatory activities. It has not been fully explored for its potential protective effects against liver injury. This study investigated whether β-sitosterol is associated with reduced hepatic injury in a short-term MTX model. The rats were arbitrarily assigned to three groups as control, MTX and MTX + β-sitosterol groups. A single intraperitoneal dose of MTX was used to induce liver toxicity, and animals subsequently received either β-sitosterol or vehicle by oral gavage once daily for ten days. Liver tissues were evaluated using semi-quantitative histopathological scoring. Plasma alanine transaminase (ALT) and malondialdehyde (MDA), as well as liver transforming growth factor-β (TGF-β), MDA, stimulator of interferon genes (STING) and extracellular signal-regulated kinase 1 (ERK-1) levels were measured. β-sitosterol treatment was associated with lower plasma ALT and MDA levels compared with the MTX group. Hepatic TGF-β, MDA, STING and ERK-1 levels were also reduced in the MTX + β-sitosterol group. Histopathology showed attenuated hepatocyte necrosis, inflammatory infiltration and early fibrotic changes. β-sitosterol was associated with reduced oxidative stress markers and lower hepatic TGF-β, STING and ERK-1 levels in this short-term MTX injury model. These findings suggest that β-sitosterol may have potential therapeutic value in mitigating MTX-related hepatotoxicity.

OBJECTIVE:To determine whether very high-dose maternal omega-3 fish oil supplementation induces sex-dependent autism-related behavioral and neurobiological changes in rat offspring. METHODS:Pregnant Sprague-Dawley rats received tap water or fish oil (60% EPA, 40% DHA; 5000 mg/kg/day) throughout gestation. Litters were standardized at birth and offspring weaned on P21. At P50, sociability (three-chamber test) and locomotion (open field) were assessed. Brain IGF-1, plasma biochemical markers, and serum testosterone were measured. Hippocampal CA1/CA3 neurons and GFAP immunoreactivity were analyzed. RESULTS:Omega-3-exposed males showed a profound sociability deficit (15.4 ± 4.8% vs. 78.3 ± 6.1%; p < 0.001), while females were unaffected. Locomotor activity was unchanged. IGF-1 increased in both sexes, with a greater rise in males. Prenatal omega-3 elevated triglycerides, uric acid, and ALT in both sexes and selectively increased cholesterol and testosterone in males. Histology revealed CA1 neuronal alterations and marked astrogliosis in exposed males. CONCLUSION:Very high-dose prenatal omega-3 intake produces a male-specific autism-like phenotype associated with IGF-1 upregulation, hippocampal glial activation, and metabolic changes, underscoring the importance of defining upper safety thresholds for prenatal omega-3 intake during pregnancy.

Hepatotoxicity is a significant adverse effect associated with long-term methotrexate (MTX) treatment, limiting its clinical utility. This study aimed to comprehensively evaluate the potential hepatoprotective effects of Otilonium Bromide (OB) against MTX-induced liver injury in an experimental rat model by integrating biochemical, molecular, and histopathological assessments. MTX administration resulted in significant structural and functional liver damage, as evidenced by elevated biochemical markers, alanine aminotransferase (ALT), transforming growth factor-beta (TGF-β), NOD-like receptor family pyrin domain-containing 3 (NLRP3), platelet-derived growth factor (PDGF), malondialdehyde (MDA) and worsened histopathological scores, including increased hepatocyte necrosis, fibrosis, and cellular infiltration. Treatment with OB significantly reduced these biochemical markers and improved histopathological changes compared to the MTX + saline group. Otilonium Bromide demonstrated hepatoprotective effects in the rat model of MTX-induced liver injury, likely through its anti-inflammatory and antifibrotic properties. These effects may be mediated by modulation of oxidative stress and the intestinal microbiome. Further studies are needed to explore its clinical applicability.

This study aims to evaluate the neuroprotective and anti-inflammatory effects of tamoxifen in mitigating neurobehavioral deficits induced by propionic acid (PPA), an autism model in rats. Specifically, the study examines tamoxifen’s impact on sociability, locomotion, neuron integrity, and inflammation within the hippocampus and cerebellum. Thirty male Wistar rats were assigned to three groups: control, PPA+saline, and PPA+tamoxifen. PPA was administered intraperitoneally to induce autism-like symptoms, followed by tamoxifen treatment in the designated group. Sociability was assessed using the three-chamber sociability test, and locomotion was measured with the open-field test. Histopathological assessments, including GFAP immunostaining and cresyl violet staining, were conducted to examine astrocyte activity and neuronal integrity in brain sections. Additionally, biochemical analyses were performed to measure oxidative stress markers and inflammatory cytokines. Tamoxifen significantly improved sociability and locomotor function compared to the PPA+saline group. Histopathological evaluation revealed tamoxifen’s potential in preserving neuronal structure, indicated by increased Purkinje cell counts and reduced glial activation. Biochemical analyses demonstrated that tamoxifen reduced oxidative stress markers such as malondialdehyde (MDA) and inflammatory cytokines, including TNF-α and iNOS, while increasing levels of brain-derived neurotrophic factor (BDNF). These findings suggest that tamoxifen may offer neuroprotective and anti-inflammatory benefits in addressing neurobehavioral and neuroinflammatory deficits associated with autism models induced by PPA. However, further studies are necessary to investigate potential gender-specific effects and optimize dosing strategies for broader therapeutic applications.

OBJECTIVE:Diabetes mellitus profoundly impairs female reproductive health by inducing uterine atrophy, follicular loss, and hormonal dysregulation. Oxidative stress and profibrotic signaling, particularly transforming growth factor-β (TGF-β), are central to this pathology, while the role of heat shock protein 70 (HSP70) remains insufficiently characterized. Alpha-lipoic acid (ALA), a mitochondrial cofactor and potent antioxidant, has shown efficacy against diabetic complications; however, its protective effects on reproductive tissues in type 1 diabetes are not well established. METHODS:Thirty adult female Wistar rats were allocated into control, diabetic, and diabetic + ALA groups (n = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg). ALA was administered orally (200 mg/kg/day) for four weeks. Histopathological evaluation focused on uterine gland degeneration, stromal fibrosis, and ovarian follicular integrity. Plasma anti-Müllerian hormone (AMH), uterine TGF-β, and ovarian HSP70 levels were quantified using ELISA. RESULTS:Streptozotocin-induced diabetes caused significant uterine gland degeneration, stromal fibrosis, ovarian follicular loss, reduced AMH, and elevated TGF-β and HSP70 (p < 0.001). ALA treatment attenuated glandular and stromal injury, reduced fibrosis, and improved follicular morphology. Biochemically, ALA increased AMH, decreased uterine TGF-β, and further upregulated ovarian HSP70, indicating activation of cytoprotective pathways. Although glucose levels remained elevated, partial glycemic reduction was observed. CONCLUSION:ALA exerts antifibrotic and cytoprotective effects in diabetic reproductive tissues, mitigating uterine and ovarian damage through modulation of TGF-β and HSP70 pathways.

Background and Objectives: Feces-induced peritonitis (FIP), a clinically relevant model of polymicrobial sepsis, induces systemic inflammation and acute lung injury (ALI). Methylene blue (MB), a phenothiazine-based compound, exhibits vasoregulatory, antioxidant, and anti-inflammatory properties in the context of sepsis. This study aimed to evaluate the protective effects of MB on pulmonary injury in a rat model of FIP-induced sepsis. Materials and Methods: Forty male Wistar rats were randomly assigned to four groups: control, FIP, FIP + Saline, and FIP + MB. MB was administered intraperitoneally at a dose of 20 mg/kg, 1 h after FIP induction. At 24 h post-induction, plasma levels of inflammatory markers [interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)], oxidative stress marker [malondialdehyde (MDA)], metabolic indicator [lactic acid], and vascular signaling marker [cyclic guanosine monophosphate (cGMP)] were measured. Lung injury was evaluated through histopathological analysis and thoracic computed tomography (CT)-based Hounsfield unit (HU) quantification, while pulmonary function was assessed via arterial blood gas analysis, including arterial oxygen pressure (PaO2) and carbon dioxide pressure (PaCO2). Results: FIP induction led to significant increases in plasma levels of IL-6, IL-1β, TNF-α, CRP, MDA, cGMP, and lactic acid, accompanied by elevated CT attenuation (HU) values and a marked reduction in arterial PaO2 and PaCO2. MB treatment significantly decreased the levels of IL-6, IL-1β, TNF-α, CRP, MDA, lactic acid, and cGMP, improved PaO2, and attenuated both histopathological lung injury and CT-assessed parenchymal density. No significant differences were observed in PaCO2 among the groups. Conclusions: MB mitigates inflammation, oxidative damage, and pulmonary dysfunction in FIP-induced sepsis. Further studies are warranted to optimize dosing and timing and to evaluate long-term outcomes.

Background and Objectives: Liver fibrosis, a chronic process caused by various pathogenic factors, including drug toxicity, metabolic disorders, and chronic inflammation, is associated with liver-related mortality rates worldwide. It has been established that methotrexate (MTX), a pharmaceutical agent utilised in the treatment of numerous diseases, induces hepatic fibrosis. Currently, there is still a paucity of clinically efficacious antifibrotic drugs for the management of hepatic fibrosis. Thus, the present research sought to evaluate the antifibrotic effects of baricitinib in a rat model of MTX-induced liver fibrosis through the yes-associated protein (YAP) pathway. Materials and Methods: A total of 36 Wistar rats were assigned to three groups (n = 12) randomly: a control group, an MTX-induced liver fibrosis group, and a baricitinib-treated group, which received 20 mg/kg/day of baricitinib following fibrosis induction. All treatments were administered for 10 days. Results: Biochemical analyses revealed significant increases in plasma alanine aminotransferase (ALT), cytokeratin-18 (CK-18), and malondialdehyde (MDA) levels, as well as liver transforming growth factor-beta (TGF-β), YAP1, and MDA levels, in the MTX-induced fibrosis group in comparison to the control group (p < 0.05). Notably, baricitinib addition significantly reduced these biomarkers (p < 0.05). A histopathological evaluation further confirmed a marked reduction in fibrosis, hepatic necrosis, and cellular infiltration in the baricitinib-treated group relative to the MTX-induced fibrosis group. Conclusions: Accordingly, our findings suggest that baricitinib mitigates MTX-induced liver fibrosis, potentially through its anti-inflammatory and antifibrotic effects mediated by the suppression of the YAP signalling pathway. These results highlight that baricitinib could be a potential treatment option for patients with liver fibrosis.

Diabetic neuropathy (DN) is a heterogeneous condition characterized by complex pathophysiological changes affecting both autonomic and somatic components of the nervous system. Inflammation and oxidative stress are recognized contributors to the pathogenesis of DN. This study aims to evaluate the therapeutic potential of dichloroacetic acid (DCA) in alleviating DN symptoms, focusing on its anti-inflammatory and antioxidant properties. Thirty-two adult male Sprague Dawley rats were divided into four groups: Control, Diabetic, and two DCA-treated groups receiving 5 mg/kg and 10 mg/kg of DCA, respectively. Diabetes was induced with streptozotocin (STZ) injections. Assessments included lipid peroxidation levels, plasma fibroblast growth factor-21 (FGF-21) and transforming growth factor-beta (TGF-β) levels, electrophysiological measurements, histological examination of the sciatic nerve, and motor function tests. Treatment with DCA significantly reduced malondialdehyde (MDA) levels, indicating decreased lipid peroxidation. Plasma TGF-β levels were also lower in the DCA-treated groups, suggesting diminished inflammation. Conversely, plasma FGF-21 levels were elevated. Electrophysiological assessments revealed enhanced compound muscle action potential (CMAP) amplitudes and reduced distal latencies in DCA-treated rats, indicative of improved nerve conduction. Histopathological examinations showed reduced perineural thickness in the sciatic nerves of DCA-treated rats, pointing to decreased fibrosis. Enhanced performance in motor function tests was observed in these rats, implying improved muscle strength and motor capacity. The study demonstrates that DCA therapy significantly reduces oxidative stress and inflammation in a rat model of DN, thereby ameliorating neuropathic symptoms. These results support the potential of DCA as a promising therapeutic agent for DN treatment. Further research is warranted to explore its clinical applications and to provide more detailed insights.

Edaravone is a potent anti-inflammatory and antioxidant agent used in amyotrophic lateral sclerosis treatment. The effect of Edaravone on absence epilepsy was investigated in WAG/Rij (Wistar Albino Glaxo from Rijswijk) rats, a genetic animals model of absence epilepsy. Twenty-eight WAG/Rij rats were randomly assigned to four groups: control, and Edaravone-treated groups receiving 1, 10, or 30 mg/kg. A tripolar electrode was inserted into the skull using the stereotaxic device for electrocorticography (ECoG) recording. Then, the animals were allowed to recover. Baseline ECoG recordings were obtained from all groups, and then Edaravone was administered at the indicated doses for 21 days. ECoG records of all groups were retaken on the 22nd day. The brain was dissected and sent for biochemical analysis at the end of the experiment. Total antioxidant status (TAS), total oxidant status (TOS), and tumor necrosis factor-alpha (TNF-α) levels in brain tissue were measured using enzyme-linked immunosorbent assay (ELISA). The administration of 1 and 10 mg/kg Edaravone decreased the number and duration of spike-wave discharges (SWDs), but 30 mg/kg Edaravone increased the number and duration of SWDs. All Edaravone doses did not change the amplitude. In the biochemical analysis, 1 and 10 mg/kg Edaravone increased TAS level and decreased TOS and TNF-α levels compared to control group. 30 mg/kg Edaravone did not affect TAS, TOS, and TNF-α levels compared to control group. The present study exhibited that low doses of Edaravone for long-term treatment reduced the incidence of SWDs in WAG/Rij rats by reducing oxidative stress and neuroinflammation. The high doses of Edaravone increased SWDs incidence in the same model.

Background and Objectives: Methotrexate (MTX) is a widely utilised pharmaceutical agent in the treatment of various malignancies and inflammatory diseases. However, its clinical utility is often constrained by its potential for hepatotoxicity. Although pyridostigmine is a well-established reversible acetylcholinesterase inhibitor, its potential therapeutic role in preventing hepatic injury remains incompletely defined. The present study aimed to investigate whether pyridostigmine provides protective effects against MTX-triggered liver damage in a rat model. Methods: Thirty-six female Wistar albino rats randomly assigned to three groups: control (n = 12), MTX + saline (n = 12), and MTX + pyridostigmine (n = 12). Hepatotoxicity was induced by a single-dose MTX injection (20 mg/kg), followed by daily oral administration of either pyridostigmine (5 mg/kg) or saline for ten consecutive days. Hepatic function markers, oxidative stress parameters, fibrosis-associated mediators, and histopathological changes were assessed. Results: Pyridostigmine significantly attenuated MTX-induced elevations in plasma alanine aminotransferase (p < 0.05) and cytokeratin-18 levels (p < 0.001), and reduced liver and plasma malondialdehyde (MDA) levels (p < 0.05). Additionally, pyridostigmine treatment resulted in reduced levels of transforming growth factor-beta (p < 0.05), bone morphogenetic protein-9 (p < 0.001), and endoglin levels (p < 0.05), as well as increased sirtuin 1 level (p < 0.05). Histopathological examination revealed that pyridostigmine treatment significantly reduced MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. Conclusions: Pyridostigmine exerted hepatoprotective effects against MTX-induced liver injury by attenuating oxidative stress, restoring SIRT1 expression, and suppressing pro-fibrotic signaling. These findings indicate that pyridostigmine may hold therapeutic potential for the prevention of MTX-associated hepatotoxicity.

Background: Diabetes mellitus adversely affects female reproductive health by inducing oxidative stress, impairing autophagy, and promoting fibrotic remodeling in ovarian and uterine tissues. Spermidine, a natural polyamine, has gained attention as an antioxidant and autophagy enhancer. This study aimed to investigate the potential protective role of spermidine against diabetes-induced reproductive injury in rats. Methods: Thirty adult female Wistar rats were randomly divided into three groups (n = 10 each): Control, Diabetes, and Diabetes + Spermidine. Diabetes was induced with streptozotocin (60 mg/kg, i.p.). After confirmation of hyperglycemia (≥250 mg/dL), rats received either saline or spermidine (40 mg/kg/day, oral gavage) for four weeks. At sacrifice, plasma anti-Müllerian hormone (AMH) levels were determined, and ovarian and uterine tissues were assessed histologically and biochemically for oxidative stress markers (GSH, MDA, Nrf2), autophagy proteins (LC3, Beclin-1), and fibrosis indicators (TGF-β, histological scoring). Results: Diabetic rats exhibited severe hyperglycemia, pronounced follicular and endometrial degeneration, increased fibrosis, reduced plasma AMH, depleted GSH, SOD, CAT, GPx and Nrf2, and elevated MDA (p < 0.001). Spermidine treatment significantly mitigated these alterations, lowering glucose levels, alleviating histopathological injury, elevating the antioxidant defense (GSH, SOD, CAT, GPx) and the Nrf2 and decreasing MDA and TGF-β concentrations (p < 0.05 vs. Diabetes). Moreover, spermidine supplementation enhanced LC3 and Beclin-1 expression, suggesting improved autophagic activity. Conclusions: Spermidine counteracts diabetes-induced ovarian and uterine damage by reinforcing antioxidant defense, stimulating autophagy, and limiting fibrosis. These findings highlight spermidine as a promising adjunctive agent to support female reproductive health under diabetic conditions.

Radiation-induced brain injury (RIBI) continues to pose a significant clinical problem linked to neuroinflammation, oxidative stress, and neuronal death. This research evaluates the neuroprotective efficacy of oxytetracycline (OTC) in mitigating RIBI, examining its effects on behavioral, histological, biochemical, and metabolic characteristics. Female Wistar albino rats were categorized into three groups: a control group, a group subjected to brain irradiation with saline, and a group subjected to brain irradiation with oxytetracycline therapy at a dosage of 30 mg/kg/day for 15 days. Behavioral results were assessed through daily sociability, open-field, and passive avoidance learning tests. Biochemical studies included the quantification of inflammatory and oxidative stress indicators, including TNF-α, malondialdehyde (MDA), and superoxide dismutase (SOD). Histopathological assessments focused on neuronal integrity and astrocytic activity in hippocampus (CA1 and CA3 areas) and cerebellar tissues. Magnetic resonance (MR) spectroscopy was used to evaluate metabolic alterations, including lactate, N-acetylaspartate (NAA), and creatine (Cr) concentrations. oxytetracycline therapy markedly decreased oxidative stress indicators, including malondialdehyde (MDA), and restored antioxidant enzyme activity (SOD). Inflammatory markers such as TNF-α, Iba-1, and TLR-4 were reduced, however levels of neurotrophic factors (NGF and NRG-1) remained constant. Improvements in behavior were seen in friendliness, memory retention, and inquisitive behaviors. Histopathological analysis indicated maintained neuronal integrity and diminished GFAP immunostaining in the hippocampus and cerebellum. MR spectroscopy revealed reduced lactate levels and normalized NAA and Cr levels, indicating metabolic stability. Thus, oxytetracycline has neuroprotective properties that act via mitigation of inflammation, decreasing oxidative stress, and maintaining neuronal integrity. Furthermore, its capacity to alleviate metabolic dysfunction enhances its prospective use in safeguarding cognitive and neurological processes. These findings underscore the therapeutic efficacy of oxytetracycline in mitigating radiation-induced cerebral damage.

Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced by cecal ligation and puncture (CLP). Thirty-six Wistar albino rats were divided into control, CLP with saline, and Fas (100 mg/kg/day intraperitoneally) groups. Biochemical, histopathological, and molecular analyses were conducted to assess kidney function, oxidative stress, and inflammation. Fas treatment significantly decreased plasma malondialdehyde and TNF-α levels, reducing oxidative stress and systemic inflammation. Kidney function markers, including BUN and creatinine, showed marked improvement. Furthermore, Fas suppressed the expression of STAT-3 and NLRP-3 in renal tissues, highlighting its role in modulating key inflammatory pathways. Histological evaluation revealed alleviated renal damage, with less tubular necrosis and interstitial inflammation in the Fas-treated group. In conclusion, Fas demonstrates significant anti-inflammatory, antioxidant, and nephroprotective effects in S-AKI, primarily by inhibiting STAT-3 and NLRP-3 signaling. These results support its potential as a therapeutic agent in sepsis-induced kidney injury and suggest the need for further clinical evaluation.

Objectives: Sepsis-induced acute kidney injury (SI-AKI) is a major contributor to morbidity and mortality among critically ill patients. This experimental study evaluated the renoprotective effects of Tranilast, an anti-inflammatory and antifibrotic agent, in a rat model of polymicrobial sepsis, with a focus on modulation of the signal transducer and activator of transcription 3 (STAT-3) signaling pathway. Methods: Thirty-six female Wistar albino rats were randomly assigned to three groups: Sham control, cecal ligation and puncture (CLP)+saline, and CLP+Tranilast (300 mg/kg/day). Sepsis was induced by CLP. Survival was monitored for five days. Biochemical parameters including plasma tumor necrosis factor alpha (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL), heat shock protein 27 (HSP-27), malondialdehyde (MDA), blood urea nitrogen (BUN), and renal STAT-3 expression were assessed via ELISA and spectrophotometric assays. Histopathological evaluation of renal tissues was performed to assess tubular injury, inflammation, and hemorrhage. Results are expressed as mean±standard error of the mean (SEM). Results: Tranilast significantly improved survival in septic rats (75% vs. 50% in CLP+saline), reduced plasma MDA and TNF-α levels, lowered BUN and NGAL concentrations, and suppressed renal STAT-3 expression (P<0.05). It also enhanced HSP-27 levels, suggesting activation of cytoprotective responses. Histological analysis demonstrated reduced tubular necrosis, luminal debris, inflammation, and hemorrhage in Tranilast-treated rats. Conclusions: Tranilast provides significant renoprotection in SI-AKI by reducing oxidative stress, inflammation, and STAT-3 activity while enhancing cytoprotective mechanisms. These findings support its potential as an adjunctive therapeutic agent for managing sepsis-related organ injury.

OBJECTIVES:In this study, we aimed to evaluate the therapeutic effect of levetiracetam (LEV), an antiepileptic drug used in the treatment of both focal and generalized epilepsy, in a propionic acid (PPA)-induced autism model by assessing social deficits, learning and memory impairments, and their neurochemical correlates. We further examined the involvement of the AMPK/SIRT1 signalling pathway as a potential molecular mechanism. MATERIAL AND METHODS:Thirty male Wistar albino rats were allocated into three groups: normal control (n = 10), PPA + saline (n = 10) and PPA + LEV (n = 10). Autism-like features were induced by intraperitoneal PPA administration (250 mg/kg/day, 5 days). LEV was administered orally (100 mg/kg/day) for 15 days. Behavioural performance (three-chamber sociability test, open-field test, passive avoidance learning), biochemical markers (malondialdehyde [MDA], tumour necrosis factor-alpha [TNF-α], brain-derived neurotrophic factor [BDNF], AMPK, and SIRT1) and histopathological changes (neuronal counts in CA1, CA3, Purkinje cells; GFAP immunostaining) were evaluated. RESULTS:In the sociability test, social interaction time decreased by 51.6% in the PPA + saline group compared to controls (67.2% ± 2.4% vs. 32.5% ± 2.1%), while LEV increased it by 121.8% vs. PPA + saline (72.1% ± 4.5%). Open-field ambulation decreased by 83% in PPA + saline (17.3 ± 3.2 vs. 2.9 ± 0.8) and increased by 158% with LEV (7.5 ± 2.16). Passive avoidance latency decreased by 76% in PPA + saline (245.9 ± 17.5 s vs. 59.2 ± 20.8 s) and increased by 180% with LEV (165.7 ± 18.3 s). MDA levels increased by 187% in PPA + saline vs. controls (49.9 ± 1.4 vs. 143.5 ± 4.7 nmol/g protein) and decreased by 31% with LEV (98.6 ± 5.4). TNF-α increased by 1012% in PPA + saline (13.1 ± 0.9 vs. 145.8 ± 10.6 pg/mg protein) and decreased by 39% with LEV (88.4 ± 3.9). BDNF decreased by 52% in PPA + saline (5.21 ± 0.9 vs. 2.48 ± 0.3 pg/mg protein) and increased by 88% with LEV (4.66 ± 0.5). AMPK decreased by 62% in PPA + saline (113.5 ± 6.3 vs. 43.2 ± 7.5 pg/mg protein) and increased by 73% with LEV (74.8 ± 2.1). SIRT1 decreased by 75% in PPA + saline (4.65 ± 0.5 vs. 1.17 ± 1.1 pg/mg protein) and increased by 132% with LEV (2.72 ± 0.8). Histologically, CA1 neuronal counts decreased by 35% in PPA + saline (67.2 ± 2.04 vs. 43.8 ± 1.1) and increased by 38% with LEV (60.5 ± 1.3). CA3 neuronal counts decreased by 31% in PPA + saline (48.5 ± 3.2 vs. 33.7 ± 1.9) and increased by 31% with LEV (44.2 ± 0.8). Purkinje cells decreased by 53% in PPA + saline (26.2 ± 0.5 vs. 12.2 ± 0.8) and increased by 68% with LEV (20.5 ± 1.1). GFAP indices in CA1, CA3 and cerebellum were elevated in PPA + saline (31.6 ± 2.4 vs. 47.5 ± 1.2; 33.4 ± 1.1 vs. 48.2 ± 0.7; 21.2 ± 1.6 vs. 32.3 ± 0.9) and reduced with LEV (40.3 ± 0.6; 39.5 ± 0.8; 28.5 ± 1.4, respectively). These therapeutic effects were accompanied by marked upregulation of the AMPK/SIRT1 pathway, which was suppressed in the PPA + saline group. CONCLUSION:LEV treatment ameliorated PPA-induced behavioural, biochemical and histological impairments, likely via anti-inflammatory, antioxidant and neuroprotective mechanisms involving activation of the AMPK/SIRT1 pathway. These findings support LEV as a potential therapeutic candidate for autism spectrum disorder.

: Radiation exposure causes neuroinflammation, oxidative stress, and neuronal loss, leading to cognitive and behavioral impairments. This study aims to evaluate the effect of niacin interventions on whole-brain irradiation (WBI)-induced cognitive and behavioral impairment. Female Wistar rats were randomly assigned to Control (Group 1), Radiation +Saline (Group 2), and Radiation +niacin (Group 3) groups. Rats in the irradiated groups (Groups 2 and 3) received a single dose of 20 Gy photon irradiation. Group 2 received water seven days after irradiation, while Group 3 received niacin (60 mg/kg, 2 mL) oral gavage for 15 days. On days 22, 23, and 24, behavioral assessments were performed, including the Open Field Test, the Sociability Test, and the Passive Avoidance Learning (PAL) task. Biochemical analyses included MDA, BDNF, TNF-α, CREB), SIRT1, and SIRT6 measured by ELISA. Histological assessments included neuronal density and GFAP immunostaining in CA1 and CA3 regions of the hippocampus and cerebellar Purkinje neurons. Radiation exposure importantly increased MDA and TNF-α levels, while SIRT1, SIRT6, BDNF, and CREB were notably reduced. This was accompanied by neuronal loss in the cerebellum and hippocampus, astrogliosis, and behavioral and cognitive deficits. Niacin treatment significantly decreased MDA and TNF-α levels while increasing BDNF, CREB, SIRT1, and SIRT6 expression, attenuating neuronal apoptosis. Immunohistochemical analysis demonstrated that niacin treatment enhanced neuronal density in the CA1 and CA3 regions of the hippocampus and cerebellar Purkinje neurons while reducing GFAP immunoreactivity in the CA1, CA3, and cerebellum following WBI. Behaviorally, niacin treatment improved social interaction, locomotor activity, and memory performance, underscoring its neuroprotective potential against WBI-induced damage. These findings suggest that niacin may ameliorate behavioral and cognitive impairments following whole brain irradiation by activating the SIRT1/CREB/BDNF or SIRT1/SIRT6/MDA/TNF-α signaling pathway.

OBJECTIVE:Alzheimer's disease is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) peptide aggregation, representing a major therapeutic target. Emerging evidence suggests certain chemotherapeutic agents may attenuate Aβ pathology. METHODS:This study investigated the effects of imatinib, a tyrosine kinase inhibitor with limited blood-brain barrier (BBB) penetration, and nilotinib, with enhanced BBB permeability, in an intracerebroventricular streptozotocin (ICV-STZ) rat model of Alzheimer's disease. Outcomes included behavioral assessments (learning latency), hippocampal CA1 and CA3 neuronal counts, and brain concentrations of tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and neuregulin-1 (NRG-1). RESULTS:ICV-STZ administration significantly elevated TNF-α and NF-κB levels and reduced BDNF and NRG-1 expression. Both imatinib and nilotinib mitigated these alterations, with imatinib demonstrating greater efficacy despite its limited BBB permeability. Imatinib and nilotinib reduced TNF-α and NF-κB levels, increased BDNF and NRG-1 expression, and significantly improved cognitive performance, with latency periods extending from 69.8 seconds in the disease model to 193.5 and 183.1 seconds, respectively. CONCLUSION:Imatinib and nilotinib ameliorated neuroinflammation, restored neurotrophic support, and improved cognitive deficits in a preclinical Alzheimer's disease model. These findings highlight the therapeutic potential of tyrosine kinase inhibitors, warranting further translational research in human studies.