Neuroprotective effect of hesperidin and its combination with coenzyme Q10 on an animal model of ketamine-induced psychosis: behavioral changes, mitochondrial dysfunctions, and oxidative stress

Background Psychosis is a complex mental illness divided by positive symptoms, negative symptoms, and cognitive decline. Clinically available medicines are associated with some serious side effects which limit their use. Treatment with flavonoids has been associated with delayed onset and development, decreased risk, or increased improvement of various neuropsychiatric disorders including psychosis with negligible side effects. Therefore, the present study was aimed to investigate the protective effects of hesperidin (flavonoid) alone or its combination with coenzyme Q10 against ketamine-induced psychotic symptoms in mice. Results Ketamine (50 mg/kg, i.p.) was given for 21 days to induce psychosis in Laca mice of either sex. Locomotor activity and stereotypic behaviors, immobility duration (forced swim test), and increased transfer latency (elevated plus maze) were performed to test the effect of hesperidin (50 mg/kg, 100 mg/kg, 200 mg/kg, p.o.) and coenzyme Q10 (20 mg/kg, 40 mg/kg, p.o.) and combination of hesperidin + coenzyme Q10 followed by biochemical and mitochondrial complexes assays. For 21 days, ketamine (50 mg/kg, i.p.) administration significantly produced increased locomotor activity and stereotypic behaviors (positive symptoms), increased immobility duration (negative symptoms) and cognitive deficits (increases transfer latency) weakens oxidative defense and mitochondrial function. Further, 21 days’ administration of hesperidin and coenzyme Q10 significantly reversed the ketamine-induced psychotic behavioral changes and biochemical alterations and mitochondrial dysfunction in the discrete areas (prefrontal cortex and hippocampus) of mice brains. The potential effect of these drugs was comparable to olanzapine treatment. Moreover, the combination of hesperidin with coenzyme Q10 and or a combination of hesperidin + coenzyme Q10 + olanzapine treatment did not produce a significant effect compared to their per se effect in ketamine-treated animals. Conclusions The study revealed that hesperidin alone or in combination with coenzyme Q10 could reduce psychotic symptoms and improve mitochondrial functions and antioxidant systems in mice, suggesting neuroprotective effects against psychosis.

The Effect of Coenzyme Q10 on Liver Injury Induced by Valproic Acid and Its Antiepileptic Activity in Rats

Valproic acid (VPA) has toxic metabolites that can elevate oxidative stress markers, and the hepatotoxicity of VPA has been reported. Coenzyme Q10 (CoQ10) is one of the most widely used antioxidants. The effect of CoQ10 on epileptogenesis and VPA hepatotoxicity were examined. Rats were randomly divided into five groups: the control group received 0.5% methylcellulose by oral gavages daily and saline by intraperitoneal injection three times weekly. The PTZ group received 1% methylcellulose by gavages daily and 30 mg/kg PTZ by intraperitoneal injection three times weekly. The valproic acid group received 500 mg/kg valproic acid by gavage and 30 mg/kg PTZ, as above. The CoQ10 group received 200 mg/kg CoQ10 by gavages daily and 30 mg/kg PTZ, as above. The Valproic acid + CoQ10 group received valproic acid and CoQ10, as above. Results: CoQ10 exhibited anticonvulsant activity and potentiated the anticonvulsant effect of VPA. CoQ10 combined with VPA induced a more significant reduction in oxidative stress and improved the histopathological changes in the brain and liver compared to VPA treatment. In addition, CoQ10 reduced the level of toxic VPA metabolites. These findings suggest that the co-administration of CoQ10 with VPA in epilepsy might have therapeutic potential by increasing antiepileptic activity and reducing the hepatotoxicity of VPA.

Practical Guidelines for Diagnosing and Treating Thyroid Disease Based on the WOMED Metabolic Model of Disease Focusing on Glycolysis and Coenzyme Q10 Deficiency—A Clinical Alternative to the 2021 Retired Clinical Practice Guidelines of the Endocrine Society

This review aims to provide a functional, metabolic view of the pathogenesis of benign thyroid disease. Here, we summarize the features of our previous publications on the “WOMED model of benign thyroid disease”. As of 2021, the current state of art indicates that the basic alteration in benign thyroid disease is a metabolic switch to glycolysis, which can be recognized using 3D-power Doppler ultrasound. A specific perfusion pattern showing enlarged vessels can be found using this technology. This switch originates from an altered function of Complex I due to acquired coenzyme Q10 deficiency, which leads to a glycolytic state of metabolism together with increased angiogenesis. Implementing a combined supplementation strategy that includes magnesium, selenium, and CoQ10, the morphological and perfusion changes of the thyroid can be reverted, i.e., the metabolic state returns to oxidative phosphorylation. Normalization of iron levels when ferritin is lower than 50 ng/mL is also imperative. We propose that a modern investigation of probable thyroid disease requires the use of 3D-power Doppler sonography to recognize the true metabolic situation of the gland. Blood levels of magnesium, selenium, CoQ10, and ferritin should be monitored. Thyroid function tests are complementary so that hypo- or hyperthyroidism can be recognized. Single TSH determinations do not reflect the glycolytic state.