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 AlsharifAshraf AlbrakatiNaif E Al OmairiAbdulraheem S AlmalkiWalaa F AlsanieZakaria Y Abd ElmageedOla A HabottaMaha S LokmanHussam A AlthagafiAbdullah A A AlghamdiAhmed E Abdel MoneimHussain AlyamiSaied K M BelalGhaliah AlnefaieAbdulhakeem S AlamriNisreen Khalid Aref AlbezrahRami B KassabAlaa Jameel A AlbarakatiKhalid Ebraheem HassanAhmad AgilPublished in: Environmental science and pollution research international (2022)
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 (Na 2 SeO 3 ) 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) + Na 2 SeO 3 (2 mg/kg), and AMPH + PDG + Na 2 SeO 3 . The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na 2 SeO 3 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 Na 2 SeO 3 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 Na 2 SeO 3 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 Na 2 SeO 3 . The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na 2 SeO 3 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.
Keyphrases
- cell death
- gene expression
- oxidative stress
- anti inflammatory
- rheumatoid arthritis
- mental health
- cerebral ischemia
- inflammatory response
- cell proliferation
- subarachnoid hemorrhage
- lipopolysaccharide induced
- brain injury
- drug induced
- diabetic rats
- uric acid
- breast cancer cells
- signaling pathway
- blood brain barrier
- high glucose
- prefrontal cortex
- amyotrophic lateral sclerosis