Therapeutic effect of finasteride through its antiandrogenic and antioxidant role in a propionic acid-induced autism model: Demonstrated by behavioral tests, histological findings and MR spectroscopy

Sever, İbrahim Halil; Özkul, Bahattin; Bozkurt, Mehmet Fatih; Erbaş, Oytun

doi:10.1016/j.neulet.2022.136622

Cited by 7 publications

(8 citation statements)

References 86 publications

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“…In a study conducted on rats, it was found that while the brain lactate level was quite high in animals with pharmacologically-induced autism, lactate levels decreased in the autism group treated with finasteride. 46 In another study conducted in humans, it was found that lactate doublets increased by 13 times on MR spectroscopy in autistic patients when compared to a healthy control group. 47 In the present study, lactate elevation was also shown in MR spectroscopy in rats with PPA-induced autism, which supports the data in the literature.…”

Section: Discussionmentioning

confidence: 97%

Lowering propionic acid levels by regulating gut microbiota with ursodeoxycholic acid appears to regress autism symptoms: an animal study

karakas

Solmaz

Bağcıoğlu

et al. 2023

Journal of Health Sciences and Medicine

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Aims: Patients with autism have altered gut microbiata, including higher frequency of bacteroidetes and clostridiales that produce of propionic acid (PPA) –a compound that is established as an autism-inducing agent. We hypothesized that lowering the PPA levels by regulating gut microbiata with ursodeoxycholic acid (UDCA) can regress the autism symptoms. The aim of this study is to examine the potential ameliorating effects of UDCA on a PPA-induced rat model of autism. Methods: Thirty male Wistar albino rats were divided into three groups: controls, PPA-induced (5 days of intraperitoneal 250 mg/kg/day dosage) autism model receiving oral saline, and PPA-induced autism model receiving oral UDCA (100 mg/kg/day). Oral treatments were applied for 15 days. At the end of the 15th day, all rats underwent behavioral tests and MR spectroscopy. At the end of the study, all animals were sacrificed and brain tissue / blood samples were collected for histopathological and biochemical analyses. Results: Sociability test, open field test and passive avoidance learning tests were impaired, similar to the autism behavioral pattern, in PPA recipients; however, results were closer to normal patterns in the PPA+UDCA group. Biochemically, MDA, TNF-alpha, IL-2, IL-17, NF-kB, lactate, NGF and NRF2 levels in brain tissues showed significant differences between controls and the PPA+Saline group, and between the PPA+Saline group and the PPA+UDCA group (p< 0.05, for all). Histopathology showed that PPA injection caused increased glial activity, neural body degeneration, decreased neural count and dysmorphic changes in hippocampal and cerebellar tissues (p

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Section: Discussionmentioning

confidence: 97%

Lowering propionic acid levels by regulating gut microbiota with ursodeoxycholic acid appears to regress autism symptoms: an animal study

karakas

Solmaz

Bağcıoğlu

et al. 2023

Journal of Health Sciences and Medicine

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“…An imaging system (Image-Pro Express 1.4.5, Media Cybernetics, Inc. USA) was used for the assessments. 8 , 33 …”

Section: Methodsmentioning

confidence: 99%

“… 7 Currently, PPA is considered as a well-established agent for the development of experimental model of ASD. 8 - 14 …”

Section: Introductionmentioning

confidence: 99%

Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study

Doğan¹,

Albayrak²,

Erbas³

2023

ALPHA PSYCHIATRY

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Objective: Autism spectrum disorder is a neurodevelopmental disease in which impaired social behaviors, impaired sociality, and restricted and repetitive behaviors are seen. Bumetanide is a loop diuretic that inhibits Na + –K + –2Cl − cotransporter 1 and it is currently used in clinical phase studies in patients with autism spectrum disorder. In present research, it is purposed to demonstrate the beneficial effects of torasemide which is another Na + –K + –2Cl − cotransporter 1 inhibitor on an experimental autism model induced with propionic acid by providing imaging and brain tissue investigations. Methods: Male Wistar rats were used in the present study (n = 30). Propionic acid of 250 mg/kg/day was administrated intraperitoneally in rats to induce autism for 5 days. Three groups were created for present study as follows: group 1, normal control (n = 10); group 2, propionic acid and saline given group (n = 10); group 3, propionic acid + tora-semide-administrated group (n = 10). Results: Torasemide group scored higher on behavioral tests compared to saline group. The brain levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-2, interleukin-17, and Nuclear Factor kappa B (NF-κB), Glial fibrillary acidic protein (GFAP) were remarkably higher in propionic acid + saline group. In histopathology assessments, torasemide group had higher neuronal count of Cornu Ammonis 1, neuronal count of Cornu Ammonis 2 in hippocampus, and Purkinje cells in cerebellum. GFAP immunostaining index (Cornu Ammonis 1) and cerebellum were lower in torasemide group. Magnetic resonance spectroscopy revealed that mean lactate value was higher in propionic acid + saline group compared to torasemide group. Conclusion: Our experimental results showed that torasemide might enhance gamma-aminobutyric acid activity. Torasemide can be considered another promising Na + –K + –2Cl − cotransporter 1 inhibitor in the treatment of autism with a longer half-life and less side effects after further studies.

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“…The exact etiology of ASD is unclear. Moreover, the current treatments are far from healing the core symptoms regarding the limited knowledge of etiology [2]. The animal models for ASD are considered to be important for the development of new treatment strategies, monitoring the effects and side effects of new agents, and understanding the exact pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin Improves the Propionic Acid-Induced Autism in Rats: The Roles of Sphingosine-1-Phosphate and Anti-inflammatory Action

Durankuş¹,

Budak²,

Albayrak³

et al. 2023

Cureus

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The aim of this study is to investigate the benefits of atorvastatin on the propionic acid-induced autism model via increasing sphingosine-1-phosphate and anti-inflammatory actions with imaging and brain tissue investigations. Materials and methodsTwenty-five mg/kg/day/rat of propionic acid (PPA) was administered intraperitoneally to 20 male Wistar rats, and 10 male Wistar rats were fed orally. Study groups were designed as follows: Group 1: Control Group (orally fed control, n=10); Group 2 (PPA+saline, n=10); Group 3 (PPA+Atorvastatin, n=10). The brain biochemical and histopathology assessments and magnetic resonance (MR) imaging were conducted across groups in order to compare them. ResultsThe PPA+Atorvastatin group was found to have significantly lower levels of brain malondialdehyde, IL-2 level, IL-17, tumor necrosis factor-alpha (TNF-α), and lactate compared to the PPA+saline group. The PPA+Atorvastatin group had higher levels of nerve growth factor and nuclear factor erythroid 2-related factor 2 (NRF-2) and sphingosine-1-phosphate. In histopathology assessments, the PPA+Atorvastatin group was found to have significantly higher neuronal counts of CA1 and CA2 in the hippocampus, and Purkinje cells in the cerebellum. ConclusionsCurrent findings suggest that atorvastatin increases sphingosine-1-phosphate levels and decreases inflammatory actions which characterize the autism rodent model implemented in this study. These preliminary results have to be confirmed by further experimental and clinical studies.

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Therapeutic effect of finasteride through its antiandrogenic and antioxidant role in a propionic acid-induced autism model: Demonstrated by behavioral tests, histological findings and MR spectroscopy

Cited by 7 publications

References 86 publications

Lowering propionic acid levels by regulating gut microbiota with ursodeoxycholic acid appears to regress autism symptoms: an animal study

Lowering propionic acid levels by regulating gut microbiota with ursodeoxycholic acid appears to regress autism symptoms: an animal study

Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study

Atorvastatin Improves the Propionic Acid-Induced Autism in Rats: The Roles of Sphingosine-1-Phosphate and Anti-inflammatory Action

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