Therapeutic potential of diosmin, a citrus flavonoid against arsenic-induced neurotoxicity via suppression of NOX 4 and its subunits.

OBJECTIVES: Water contaminated with arsenic affected millions of people worldwide and arsenic exposure is related to various neurological disorders. Hence, the current study was planned to investigate the neuroprotective activity of diosmin (DSN) against arsenic induced neurotoxicity as an attempt to identify therapeutic intervention to combat arsenicism. MATERIALS AND METHODS: Sodium arsenite an inducer of neurotoxicity was administered orally (13 mg/kg) and DSN treatment at two selected doses (50 and 100 mg/kg) was done for 21 days. Behavioral and biochemical variations were examined by various parameters. Furthermore, histopathological and immunohistochemistry studies were done with the brain sections. RESULTS: The behavioral studies evidenced that arsenic has suppressed the exploratory behavior and motor coordination in rats and DSN treatment has recovered the behavioral changes to normal. Arsenic administration has also found to induce oxidative stress and DSN co-treatment has ameliorated the oxidative stress markers. Interestingly, depleted levels of neurotransmitters were observed with the arsenic and it was restored back by the DSN treatment. Histopathological alterations like pyknosis of the neuronal cells were identified with arsenic exposure and subsided upon DSN co administration. Immunohistochemical studies have revealed the expression of NOX4 and its gp91phox and P47phox subunits and its suppression by DSN treatment may be the key therapeutic factor of it. CONCLUSIONS: Treatment with DSN showed a beneficial effect in protecting against arsenic-induced neurotoxicity by suppressing the toxicity changes and the antioxidant effect of DSN might be attributed to its ability of suppressing NOX4 and its subunits.

Devil's claw (Harpagophytum procumbens) ameliorates the neurobehavioral changes and neurotoxicity in female rats exposed to arsenic.

Over 200 million people are exposed to arsenic worldwide in their daily lives. Arsenic is a toxic ubiquitous metalloid distributed in the ground water. From the last few decades it is obtaining considerable attention for its severe neurotoxic properties. In this study the neuroprotective efficacy of devil's claw (DCW), a potent antioxidant has been investigated against arsenic induced neurotoxicity in female rats. Neurotoxicity was established by oral administration of 13 mg/kg sodium arsenite. The animals were divided into five groups (n = 6) including normal control, disease/arsenic control, standard treatment (Apocynin, 10 mg/kg), DCW treatment I (DCW, 200 mg/kg) and DCW treatment II (DCW, 400 mg/kg). Exploratory, anxiety and motor coordination related behavior of the animals was assessed using hole-board, forced swimming, beam walk and elevated plus maze tests. Findings revealed that DCW treatment ameliorated anxiety and motor in-coordination in the rats compared to the arsenic control group. In addition, arsenic induced a significant oxidative stress in arsenic only treated group, whereas co-administration with DCW the oxidative stress was reduced prominently. Arsenic control group produced gliosis and nuclear pyknosis of the brain cells which were prominently suppressed with the treatment of DCW for 21 days. The activity of DCW was in correlation with the concentration of harpagoside in the serum estimated by the HPLC method, supports that harpagoside was the active constituent responsible for neuroprotective effect. Further findings are required to understand the molecular mechanisms involved in neuroprotective effect of harpagoside and DCW.