Nano-hesperetin attenuates ketamine-induced schizophrenia-like symptoms in mice: participation of antioxidant parameters.

Rationale: Antioxidant natural herb hesperetin (Hst) offers powerful medicinal properties. Despite having noticeable antioxidant properties, it has limited absorption, which is a major pharmacological obstacle.

Objectives: The goal of the current investigation was to determine if Hst and nano-Hst might protect mice against oxidative stress and schizophrenia (SCZ)-like behaviors brought on by ketamine (KET).

Methods: Seven treatment groups (n=7) were created for the animals. For 10 days, they received distilled water or KET (10 mg/kg) intraperitoneally (i.p). From the 11th to the 40th day, they received daily oral administration of Hst and nano-Hst (10, 20 mg/kg) or vehicle. With the use of the forced swimming test (FST), open field test (OFT), and novel object recognition test (NORT), SCZ-like behaviors were evaluated. Malondialdehyde (MDA) and glutathione levels and antioxidant enzyme activities were assessed in the cerebral cortex.

Results: Our findings displayed that behavioral disorders induced by KET would be improved by nano-Hst treated. MDA levels were much lower after treatment with nano-Hst, and brain antioxidant levels and activities were noticeably higher. The mice treated with nano-Hst had improved outcomes in the behavioral and biochemical tests when compared to the Hst group.

Conclusions: Our study's findings showed that nano-Hst had a stronger neuroprotective impact than Hst. In cerebral cortex tissues, nano-Hst treatment dramatically reduced KET-induced (SCZ)-like behavior and oxidative stress indicators. As a result, nano-Hst may have more therapeutic potential and may be effective in treating behavioral impairments and oxidative damage brought on by KET.