Hedgehog signaling is a promising target for the treatment of hepatic fibrogenesis: a new management strategy using itraconazole-loaded nanoparticles.

Liver fibrosis is a disease with a great global health and economic burden. Existing data highlights itraconazole (ITRCZ) as a potentially effective anti-fibrotic therapy. However, ITRCZ effect is hindered by several limitations, such as poor solubility and bioavailability. This study aimed to formulate and optimize chitosan nanoparticles (Cht NPs) loaded with ITRCZ as a new strategy for managing liver fibrosis. ITRCZ-Cht NPs were optimized utilizing a developed 22 full factorial design. The optimized formula (F3) underwent comprehensive in vitro and in vivo characterization. In vitro assessments revealed that F3 exhibited an entrapment efficiency of 89.65% ± 0.57%, a 169.6 ± 1.77 nm particle size, and a zeta potential of +15.93 ± 0.21 mV. Furthermore, in vitro release studies indicated that the release of ITRCZ from F3 adhered closely to the first-order model, demonstrating a significant enhancement (p-value < 0.05) in cumulative release compared to plain ITRCZ suspension. This formula increased primary hepatocyte survival and decreased LDH activity in vitro. The in vivo evaluation of F3 in a rat model of liver fibrosis revealed improved liver function and structure. ITRCZ-Cht NPs displayed potent antifibrotic effects as revealed by the downregulation of TGF-ß, PDGF-BB, and TIMP-1 as well as decreased hydroxyproline content and α-SMA immunoexpression. Anti-inflammatory potential was evident by reduced TNF-α and p65 nuclear translocation. These effects were likely ascribed to the modulation of Hedgehog components SMO, GLI1, and GLI2. These findings theorize ITRCZ-Cht NPs as a promising formulation for treating liver fibrosis. However, further investigations are deemed necessary.

10 years of experience in adopting, implementing and evaluating progress testing for Saudi medical students.

Objectives: The progress test (PT) is a comprehensive examination that is designed to match the knowledge acquisition necessary at graduation and monitors progress during the entire period of an undergraduate program. Qassim College of Medicine (QCM) began using the multi-institutional PT in the Kingdom of Saudi Arabia (KSA). This study aimed to determine if the PT can be utilized to assess the progress of medical students at different Saudi medical colleges with different educational approaches, as well as whether this testing modality could be accepted by other colleges. Methods: Beside the establishment of a PT committee, comprehensive blueprinting was crafted to sample 200 A-type multiple choice questions (MCQs) from different disciplines. The PT is a paper-and-pencil model and is answered in a 4-h period. All PT items followed a uniform design. Results: In total, 13 rounds of the progress test have been conducted. The number of participating colleges increased from three (with 285 students) in the first test (May 2012) to more than 20 (with >6000 students) in the ninth round (February 2017). The average % scores for first-year students ranged from 3.0% to 7.9% while the average scores for fifth-year students ranged from 34.0% to 43.0%. Conclusion: The conduction of this meticulously crafted test to evaluate knowledge achievement at medical graduation is a fruitful tool and helps to provide constructive feedback for test-takers and other stakeholders relating to their relative positions among other fellows at the national level.

The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections.

BACKGROUND: The defense mechanisms of the urinary tract are attributed mainly to the innate immune system and the urinary tract urothelium which represent the first line of defense against invading pathogens and maintaining sterility of the urinary tract. There are only a few publications regarding cathelicidin (LL-37) and a urinary tract infection (UTI). This study was done to investigate the plasma and urine levels of human LL-37 in patients with UTI. METHODS: A case-control study was conducted at Omdurman Hospital, Sudan during the period from August 2014 to May 2017. The cases were patients with confirmed UTI and the controls were healthy volunteers without UTI. Sociodemographic and clinical data were obtained from each participant using questionnaires. Urine cultures and antimicrobial susceptibility were tested. Plasma and urine levels of LL-37 were determined using an enzyme-linked immunosorbent assay (ELISA) kit. SPSS (version 16.0) was used for analyses. RESULTS: Cases and controls (87 in each arm) were matched according to their basic characteristics. Compared with controls, the median (inter-quartile) LL-37 level in plasma [2.100 (1.700-2.700) vs. 1.800 (1.000-2.200) ng/ml, P = 0.002] and in urine [0.900 (0.300-1.600) vs. 0.000 (0.000-1.000) ng/mg creatinine, P < 0.001] was significantly higher in cases. There was no significant difference in the median plasma [2.1 (1.7-2.9) vs. 2.000 (1.700-2.400) ng/ml, P = 0.561] and urine [0.850 (0.275-2.025) vs. 0.900 (0.250-1.350) ng/mg creatinine, P = 0.124]. The uropathogenic Escherichia coli (UPEC) was the predominant isolate, n = 38 (43.7%). LL-37 levels between the E. coli isolates and the other isolated organisms. There was no significant correlation between plasma and urine LL-37 levels (r = 0.221), even when the data of the cases were analyzed separately. CONCLUSION: LL-37 is notably increased among patients with UTI compared with normal control subjects. Severity of UTI increases the levels of LL-37. The increased level was not only in the patient's urine, but has also been observed in the patient's plasma. Detection of increased levels of LL-37 could help to differentiate subjects with suspected UTI. Accordingly, LL-37 could act as a good marker for diagnosing UTIs.

Lactoferrin from Camelus dromedarius Inhibits Nuclear Transcription Factor-kappa B Activation, Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Stimulated Human Chondrocytes.

BACKGROUND: Osteoarthritis (OA) is a progressive joint disorder, which remains the leading cause of chronic disability in aged people. Nuclear factor-kappa B (NF)-κB is a major cellular event in OA and its activation by interleukin-1ß (IL-1ß) plays a critical role in cartilage breakdown in these patients. OBJECTIVE: In this study, we examined the effect of lactoferrin on NF-κB activation, cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production in stimulated human articular chondrocytes. MATERIALS AND METHODS: Human chondrocytes were derived from OA articular cartilage and treated with camel lactoferrin and then stimulated with IL-1ß. Gene expression was determined by TaqMan assays and protein expression was studied by Western immunoblotting. NF-κB activity and PGE2 levels were determined by ELISA based assays. NF-κB activity was also determined by treatment of chondrocytes with NF-κB specific inhibitor Bay 11-7082. RESULTS: Lactoferrin inhibited IL-1ß-induced activation and nuclear translocation of NF-κB p65 in human OA chondrocytes. Lactoferrin also inhibited mRNA/protein expression of COX-2 and production of PGE2. Moreover, Bay 11-7082 also inhibited IL-1ß-induced expression of COX-2 and production of PGE2. The inhibitory effect of lactoferrin on the IL-1ß induced expression of COX-2 or production of PGE2 was mediated at least in part via suppression of NF-κB activation. CONCLUSIONS: Our data determine camel lactoferrin as a novel inhibitor of IL-1ß-induced activation of NF-κB signaling events and production of cartilage-degrading molecule PGE2 via inhibition of COX-2 expressions. These results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA and other degenerative/inflammatory diseases. SUMMARY: Lactoferrin shows anti-arthritic activity in IL-1ß stimulated primary human chondrocytes.Lactoferrin inhibits IL-1ß-induced NF-κB activation.Lactoferrin inhibits production of cartilage degrading PGE2 via inhibition of COX-2 expression. Abbreviations Used: OA: Osteoarthritis IL-1ß: Interleukin-1 beta NF-κB: Nuclear factor-kappa B COX-2: cyclooxygenase-2 PGE2: prostaglandin E2.

Impact of anti-peroxynitrite-damaged-thymidine-monophosphate antibodies on disease activity in patients with systemic lupus erythematosus.

Present study probes the role of peroxynitrite (ONOO(-))-modified thymidine-5'-monophosphate (TMP) in SLE patients with different disease activity scores according to the SLE Disease Activity Index (SLEDAI). Serum analysis showed significant increased number of subjects positive for anti-ONOO(-)-TMP-protein antibodies in SLE patients with different SLEDAI scores. Interestingly, the levels of these antibodies were significantly higher among SLE patients, whose SLEDAI scores were ≥20. In addition, a significant correlation was observed between the levels of anti-ONOO(-)-TMP-protein antibodies and the SLEDAI score (r = 0.595, p < 0.0001). In short, this study shows a positive association between anti-ONOO(-)-TMP-protein antibodies and SLEDAI. The stronger response observed in patients with higher SLEDAI scores suggests that anti-ONOO(-)-TMP-protein antibodies may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.

Therapeutic targets for rheumatoid arthritis: Progress and promises.

Recent therapeutic advancements in understanding of molecular and cellular mechanisms of rheumatoid arthritis (RA) have highlighted the strategies that aim to inhibit the harmful effects of up-regulated cytokines or other inflammatory mediators and to inhibit their associated signaling events. The utility of cytokine as therapeutic targets in RA has been unequivocally demonstrated by the success of tumor necrosis factor (TNF)-α blockade in clinical practice. Partial and non-responses to TNF-α blocking agents, however, together with the increasing clinical drive to remission induction, requires that further therapeutic targets be identified. Numerous proinflammatory mediators with their associated cell signaling events have now been demonstrated in RA, including interleukin (IL)-1 and IL-12 superfamilies. Continued efforts are ongoing to target IL-6, IL-15 and IL-17 in clinical trials with promising data emerging. In the present review, we focus on IL-7, IL-18, IL-32 and IL-10 family of cytokines (IL-19, IL-20 and IL-22) as they are implicated in contributing to the pathogenesis of RA, which could be targeted and offer new therapeutic options for RA therapy. Recent evidences also suggest that multiligand receptor for advanced glycation end products (RAGE), several adipokines and various components of immune system play a critical role in the pathophysiology of RA; therefore we have also highlighted them as therapeutic targets for RA therapy. Components of subcellular pathways, involve in nuclear transcription factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway have also been discussed and offer several novel potential therapeutic opportunities for RA.

Stress-mediated modulations in dopaminergic system and their subsequent impact on behavioral and oxidative alterations: an update.

CONTEXT: Stress-induced changes in the dopaminergic system and subsequent enhancement of oxidative load and behavior are associated with a wide range of central and peripheral nervous disorders. Dopamine acts as a key neurotransmitter in the brain plays an important role in the regulation of motor and limbic functions. OBJECTIVE: This article reviews the effect of stress on central dopaminergic system and its subsequent impact on the alterations in behavior and oxidative stress. METHODS: A literature survey in PubMed (Bethesda, MD), Scopus (Philadelphia, PA), SciFinder (Columbus, OH) and Google Scholar (PMV, CA) was performed to gather information regarding the role of stress on central dopaminergic system and its associated behavioral and oxidative alterations. RESULTS: Our collective data on behavioral studies and oxidative distress in stressful conditions show the functional reduction in dopaminergic neuronal system that could be one of the factors for the development of stress-induced motor suppression. Collectively, stress caused significant behavioral and oxidative alterations via suppression of neuronal functions of the central dopaminergic system. CONCLUSIONS: This study provides an insight into the overall pathophysiological alterations in neuronal functions of the central dopaminergic system caused by acute and chronic unpredictable stress that, in our opinion, represent optimal utility as future therapeutic targets for neurodegenerative disorders.

Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-α, interleukin-6 and oxidative status biomarkers in rats: protective effect of curcumin.

UNLABELLED: The present study was designed to investigate the effect of CdCl2-polluted drinking water (40 mg CdCl2/L) on the level of TNF-α and IL-6, as well as oxidative status biomarkers in plasma of rats. The possible protective effect of oral administration of curcumin (50 mg/kg body weight/day) was assessed. Results illustrated that Cd exposure significantly elevated the plasma levels of TNF-α and IL-6 (p<0.001) as compared to normal rats. Also, Cd administration resulted in a significant elevation in the lipid peroxidation and markedly reduction in the activities of SOD and catalase as well as the level of glutathione and total antioxidant capacity in plasma. The co-treatment of Cd with curcumin significantly reduced the levels of TNF-α and IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Negative correlation between IL-6 or TNF-α was and the plasma activities of catalase, SOD and the level of total antioxidant capacity were found in rats exposed to Cd. CONCLUSION: Cadmium toxicity induced the release of TNF-α and IL-6 which is associated with systemic oxidative stress. This may be involved in the mechanism of the Cd toxicity. On the other hand, the findings suggest the curative action of curcumin against Cd toxicity.

Cucurbitacins - a promising target for cancer therapy.

During the last decades a large number of cucurbitacins have been isolated from various plant species belonging to other plant families than Cucurbitaceae. Although the roots and the fruits of plant belong to these Cucurbitaceae species are very bitter, they have been used as folk medicines in some countries because of their wide spectrum of pharmacological activities such as anti-inflammation and anticancer effects. In the last ten years, cucurbitacins had been shown to inhibit proliferation and induced apoptosis utilizing a long array of in vitro and in vivo cancer cell models. Several molecular targets for cucurbitacins have been discovered, such as fibrous-actin, signal transducer and activator of transcription (STAT), cyclooxygenase-2, etc. This review aimed at elucidating the natural sources of some cucurbitacin compounds, their chemical structure and derivatives, physical properties, biological activities and mechanism by which they reduce the proliferation human cancer cells. This widens our armaments against a devastating disease that we are failing to face.

ACE I/D and eNOS E298D gene polymorphisms in Saudi subjects with hypertension.

BACKGROUND: Hypertension has a multifactorial background based on genetic and environmental interactive factors. OBJECTIVES: We aimed to test for the association of the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) gene polymorphisms with hypertension. SUBJECTS AND METHODS: Participants included 120 Saudi patients with hypertension and 250 normal healthy controls. For all participants, DNA was processed for characterization of ACE I/D and eNOS E298D gene polymorphisms. RESULTS: Hypertensive cases showed a significantly higher frequency of the ACE mutant D allele carriage (98.3% vs. 92.4%, p = 0.028, OR = 4.8). Cases with hypertension associated with diabetes and obesity showed 100% mutant D allele carriage. Regarding the eNOS E298D polymorphism, the frequency of the mutant D allele carriage was only observed to be higher among cases with hypertension associated with diabetes and obesity, in comparison with controls, yet not reaching statistical significance (41.2% vs. 34%, p > 0.05). CONCLUSIONS: There is increased frequency of ACE and eNOS mutant allele carriage among Saudi patients affected with hypertension, particularly if accompanied by obesity and diabetes.

Association of MTHFR C677T and A1298C gene polymorphisms with hypertension.

OBJECTIVES: To check for the association of genetic polymorphisms related to the methylenetetrahydrofolate reductase (MTHFR) gene namely C677T and A1298C with hypertension in Saudi affected subjects from Qassim region. SUBJECTS AND METHODS: Participants included 123 Saudi hypertensive cases (83 males and 40 females) in addition to 250 (142 males and 108 females) unrelated healthy controls from the same locality. Their age mean ±SD was 50.93 ± 15.43 years. For all subjects, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T and A1298C gene polymorphisms RESULTS: Total cases showed significantly higher carriage rate for the mutant allele 677T compared to controls (40.7% vs. 26%, OR=1.9, 95% CI= 1.2-3.1) with a lower frequency of the wild type 677CC genotype (59.3% vs. 74%, p=0.004). The same was observed among cases-subgroups of hypertension associated with obesity with a notably higher odds ratio (OR=2.6, 95% CI=1.3-5.01, p=0.004). Total cases showed also significantly higher frequency of mutant 1298 C allele carriage rate compared to controls (59.3% vs. 42.4%, OR=1.98, 95% CI= 1.3-3.1) with a lower frequency of the normal AA genotype (40.7% vs. 57.6%, p=0.003). The same was observed among cases-subgroups of hypertension associated with both diabetes and obesity and among cases of hypertension with obesity, also with higher odds ratio (OR=2.6 and 2.2 respectively). CONCLUSION: This work showed that genetic polymorphisms related to the MTHFR gene are associated with the risk of hypertension particularly when accompanied with obesity and diabetes among Saudi subjects.

Central dopaminergic system and its implications in stress-mediated neurological disorders and gastric ulcers: short review.

For decades, it has been suggested that dysfunction of dopaminergic pathways and their associated modulations in dopamine levels play a major role in the pathogenesis of neurological disorders. Dopaminergic system is involved in the stress response, and the neural mechanisms involved in stress are important for current research, but the recent and past data on the stress response by dopaminergic system have received little attention. Therefore, we have discussed these data on the stress response and propose a role for dopamine in coping with stress. In addition, we have also discussed gastric stress ulcers and their correlation with dopaminergic system. Furthermore, we have also highlighted some of the glucocorticoids and dopamine-mediated neurological disorders. Our literature survey suggests that dopaminergic system has received little attention in both clinical and preclinical research on stress, but the current research on this issue will surely identify a better understanding of stressful events and will give better ideas for further efficient antistress treatments.

Frequency of thrombophilic genetic polymorphisms among Saudi subjects compared with other populations.

Thrombophilic mutations increase the tendency toward thromboembolic disease. The aim of this study was to estimate the prevalence of the genetic variants related to thrombophilia among Saudis compared with other populations. Real-time polymerase chain reaction (PCR) genotyping was carried out to determine the polymorphic variants of factor V Leiden 1695G/A, prothrombin 20210G/A, plasmin activator inhibitor 1 4G/5G, methylene tetrahydrofolate reductase (MTHFR) 677C/T, MTHFR 1298A/C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) among a representative sample of healthy Saudi subjects. Carraige rate for each of the mutant variants of factor V Leiden (FVL) and FII genes constituted 2% of the surveyed subjects giving an allele frequency of 0.01, homozygous forms of plasminogen activator inhibitor-1 (PAI-1) gene 4G/4G, MTHFR 677TT, 1298CC, and ACE DD were present among 7.7, 2.55, 7, and 51.8% of subjects with a mutant allele frequency of 0.4, 0.19, 0.29, and 0.73, respectively. This study showed that the Saudi population has a peculiar pattern regarding thrombophilic mutations that might warrant additional considerations for prophylaxis.

CYP2J2 -50 G/T and ADRB2 G46A gene polymorphisms in Saudi subjects with hypertension.

BACKGROUND: Hypertension is a result of complex factors including multiple genetic polymorphisms. OBJECTIVE: This study aims to check for the association of genetic polymorphisms of the cytochrome P450 2J2 (CYP 2J2) and beta-2-adrenergic receptor (ADRB2) genes with hypertension among Saudi subjects. SUBJECTS AND METHODS: This study included 116 cases with documented hypertension of at least 1 year duration. Their data were compared to that of 250 unrelated healthy nonhypertensive subjects from the same locality. For all participants, DNA was extracted and analyzed using real time polymerase chain reaction technique for the identification of genotypic and allelic variants of the CYP2J2 -50 G/T and ADRB2 G46A genes. RESULTS: Hypertensive cases showed a significantly higher frequency of mutant CYP2J2 -50 T allele carriage (TT and GT genotypes) compared with controls (odds ratio [OR]=3.7, p=0.0003). The same was observed among subgroups of hypertension associated with diabetes and obesity (OR=3.6, p=0.007) and cases with isolated hypertension (OR=8.4, p=0.0002). On the other hand, hypertensive cases, whether being isolated or associated with obesity and/or diabetes, showed a nonsignificant difference from controls in relation to all genotypic variants related to the ADRB2 G46A polymorphism (p>0.05). CONCLUSION: This study showed positive association of CYP2J2 gene polymorphism with hypertension among Saudi cases.

Bone morphogenetic protein-2 will be a novel biochemical marker in urinary tract infections and stone formation.

OBJECTIVES: To investigate the role of bone morphogenetic protein-2 (BMP-2) in patients with urinary tract infection (UTI) and renal stone in relation to Tamm-Horsfall protein (THP) and osteopontin (OPN). DESIGN AND METHODS: ELISA kits were used to determine these markers in serum and urinary samples of 20 patients with UTI, 15 with renal stone and 10 controls. RESULTS: BMP-2 significantly increased in serum of patients who had UTI (P=0.05) and renal stone (P=0.01). In the case of UTI, serum BMP-2 at cutoff 44 pg/mL had sensitivity and specificity (92%, 80%), while cystatin C at cutoff 525 ng/mL showed sensitivity and specificity (85%, 91%). THP is a good predictor of renal diseases (P<0.001) by regression analysis. It is also the most sensitive urinary marker for UTI with sensitivity and specificity (94%, 75%) at cutoff 305 ng/mL. CONCLUSION: Combination of serum BMP-2 and cystatin C are more sensitive and accurate for early diagnosis of renal infection and damage.

Effect of students' learning styles on classroom performance in problem-based learning.

INTRODUCTION: Since problem-based learning (PBL) sessions require a combination of active discussion, group interaction, and inductive and reflective thinking, students with different learning styles can be expected to perform differently in the PBL sessions. METHODOLOGY: Using "Learning Style Inventory Questionnaire," students were divided into separate active and reflective learner groups. Tutors were asked to observe and assess the students' behavioral performance during the PBL sessions for a period of 5 weeks. A questionnaire of 24 items was developed to assess students' behavioral performance in PBL sessions. RESULTS: Active students tended to use multiple activities to obtain the needed information were more adjusted to the group norms and regulation and more skillful in using reasoning and problem-solving skills and in participation in discussion. On the other hand, reflective students used independent study more, listened actively and carefully to others and used previously acquired information in the discussion more frequently. Formative assessment quizzes did not indicate better performance of either group. There were no significant gender differences in PBL behavioral performance or quizzes' scores. CONCLUSION: Active and reflective learners differ in PBL class behavioral performance but not in the formative assessment. We recommend that students should be informed about their learning style and that they should learn strategies to compensate for any lacks in PBL sessions through self-study. Also, educational planners should ensure an adequate mix of students with different learning styles in the PBL groups to achieve PBL desired objectives.

Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy.

OBJECTIVE: To compare efficacy between double-dose methotrexate and single-dose methotrexate for treatment of tubal ectopic pregnancy (EP). METHODS: Between March 2008 and February 2011,157 patients who had tubal EP diagnosed by a non-laparoscopic approach and were hemodynamically stable were enrolled in a prospective study in Qassim, Saudi Arabia. The participants were randomized to receive either double-dose (50mg/m(2) intramuscularly on days 0 and 4; group 1) or single-dose (50mg/m(2) intramuscularly on day 0; group 2) methotrexate. Serum human chorionic gonadotropin (ß-hCG) levels were followed until negative. RESULTS: The overall success rate was comparable between groups 1 and 2 (88.6% versus 82.0%, P=0.1). The duration of follow up until negative ß-hCG was shorter in group 1 (P=0.001). Receiver operative characteristics showed that higher cut-off levels of ß-hCG and gestational mass diameter were associated with successful outcome in group 1. Among participants with initial ß-hCG of 3600-5500 mIU/mL, the success rate was higher in group 1 (P=0.03). There was no significant difference between groups in adverse effects. CONCLUSION: For treatment of EP, double-dose methotrexate had efficacy and safety comparable to that of single-dose methotrexate; it had better success among patients with moderately high ß-hCG and led to a shorter follow up.

Neuroprotective and anti-stress effect of A68930 in acute and chronic unpredictable stress model in rats.

The neurorescuing effect of A68930 (a potent selective D(1) agonist) and its role on the regulation of hypothalamus-pituitary-adrenal (HPA)-axis have been investigated. Acute (AS) and chronic unpredictable (CUS) stress models were used to evaluate the effect of A68930 on HPA-axis regulation in relation to the change in the fiber density and number of immunoreactive (ir) neurons of tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) in the dopamine (DA) and GR rich brain regions in rats. CUS caused a significant decrease in the number of TH ir neurons in the striatum, medial forebrain bundle, ventral tegmental area and substansia nigra and GR in the cortex, striatum and hippocampus as compared to the non-stress controls (NS). Administration of A68930 (0.25mg/kg i.p.) significantly normalized these CUS-induced alterations. We also examined the role of A68930 on stress-induced brain oxidative status. AS enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the cortex and striatum, while CUS reduced the activities of SOD and catalase (CAT) in the cortex, striatum and hippocampus, when compared with NS. Increased GSH-Px activity, with reduced glutathione and increased lipid peroxidation was observed in both AS and CUS in selected brain regions as compared to NS. Administration of A68930 normalized the antioxidant enzyme activities, replenished GSH and decreased the extent of lipid peroxidation. In conclusion, present findings suggest that the stress-induced immunoreactivity of TH and GR in distinct brain regions are modulated by A68930 leading to the normalization of HPA-axis response. Ours results show the therapeutic importance of DA D(1) agonist in stress-induced dopaminergic-related neurological disorders. A68930 also influenced the brain antioxidant machinery probably through the restoration of stress-induced changes in the dopaminergic system and its crosstalk with GR.