Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats

Khalaf F Alsharif; Ashraf Albrakati; Naif E Al Omairi; Abdulraheem S Almalki; Walaa F Alsanie; Zakaria Y Abd Elmageed; Ola A Habotta; Maha S Lokman; Hussam A Althagafi; Abdullah A A Alghamdi; Ahmed E Abdel Moneim; Hussain Alyami; Saied K M Belal; Ghaliah Alnefaie; Abdulhakeem S Alamri; Nisreen Khalid Aref Albezrah; Rami B Kassab; Alaa Jameel A Albarakati; Khalid Ebraheem Hassan; Ahmad Agil

doi:10.1007/s11356-022-22409-x

Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats

Environ Sci Pollut Res Int. 2023 Jan;30(3):7987-8001. doi: 10.1007/s11356-022-22409-x. Epub 2022 Sep 1.

Authors

Khalaf F Alsharif¹, Ashraf Albrakati², Naif E Al Omairi³, Abdulraheem S Almalki⁴, Walaa F Alsanie¹, Zakaria Y Abd Elmageed⁵, Ola A Habotta⁶, Maha S Lokman⁷, Hussam A Althagafi⁸, Abdullah A A Alghamdi⁹, Ahmed E Abdel Moneim¹⁰, Hussain Alyami³, Saied K M Belal¹¹, Ghaliah Alnefaie¹², Abdulhakeem S Alamri¹, Nisreen Khalid Aref Albezrah¹³, Rami B Kassab⁸, Alaa Jameel A Albarakati¹⁴, Khalid Ebraheem Hassan¹², Ahmad Agil¹⁵

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
² Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia. a.albrakati@tu.edu.sa.
³ Department of Internal Medicine, College of Medicine, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
⁴ Department of Chemistry, Faculty of Science, Taif University, Taif, 21974, Saudi Arabia.
⁵ Department of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA, 71203, USA.
⁶ Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
⁷ Biology Department, College of Science and Humanities, Prince Sattam Bin Abdul Aziz University, Alkharj, Saudi Arabia.
⁸ Department of Biology, Faculty of Science and Arts, Al-Baha University, Almakhwah, Al-Baha, Saudi Arabia.
⁹ Department of Biology, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia.
¹⁰ Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan, 11795, Egypt.
¹¹ Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
¹² Department of Pathology, College of Medicine, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
¹³ Department of Obstetric and Gynecology, Medicine College, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia.
¹⁴ Surgery Department, College of Medicine, Al-Qunfudah Branch, Umm Al Qura University, Makkah, Saudi Arabia.
¹⁵ Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18071, Granada, Spain.

PMID: 36048389
DOI: 10.1007/s11356-022-22409-x

Abstract

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na₂SeO₃) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na₂SeO₃ (2 mg/kg), and AMPH + PDG + Na₂SeO₃. The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na₂SeO₃ significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na₂SeO₃ improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na₂SeO₃ displayed markedly lower IL-1β and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na₂SeO₃. The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na₂SeO₃ may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery.

Keywords: Apoptosis; Neuroinflammation; Oxidative stress; Prodigiosin; Schizophrenia; Selenium.

MeSH terms

Amphetamine / pharmacology
Animals
Antioxidants / pharmacology
Dietary Supplements
Oxidative Stress
Prodigiosin
Rats
Selenium* / pharmacology

Substances

Selenium
Prodigiosin
Antioxidants
Amphetamine