Neuroprotective Effects of Nano-Curcumin against Cypermethrin Associated Oxidative Stress and Up-Regulation of Apoptotic and Inflammatory Gene Expression in Rat Brains

Abstract

Cypermethrin (CPM) is the most toxic synthetic pyrethroid that has established neurotoxicity through oxidative stress and neurochemical agitation in experimental rats. The toxic effects are supposed to be mediated by modifying the sodium channels, reducing Na-K ATPase, acetylcholine esterase (AchE), and monoamine oxidase (MAO). The use of curcumin nanoparticles (NC) that have potent antioxidant, anti-inflammatory and antiapoptotic properties with improved bioavailability attenuates neurotoxicity in rat brains. To test this hypothesis, animals were divided into five groups, each having six animals. Group-I control received vehicle only, while Group-II was treated with 50 mg/kg CPM. Group-III and Group-IV received both CPM and NC 2.5 mg/kg and 5 mg/kg, respectively. Group-V received 5 mg of NC alone. The CPM and NC were given by oral route. Afterwards, brain antioxidant status was measured by assessing lipid peroxidation (LPO), 4-HNE, glutathione reduced (GSH), antioxidant enzyme catalase, and superoxide dismutase (SOD) along with neurotoxicity markers Na-K ATPase, AchE, and MAO. Inflammation and apoptosis indices were estimated by ELISA, qRT-PCR, and immunohistochemistry, while morphologic changes were examined by histopathology. Observations from the study confirmed CPM-induced neurotoxicity by altering Na-K ATPase, AchE, and MAO, and by decreasing the activity of antioxidant enzymes and GSH. Oxidative stress marker LPO and the level of inflammatory interleukins IL-6, IL-1β, and TNF-α were notably high, and elevated expressions of Bax, NF-kB, and caspase-3 and -9 were reported in CPM group. However, NC treatment against CPM offers protection by improving antioxidant status and lowering LPO, inflammation, and apoptosis. The neurotoxicity marker’s enzyme successfully attenuated after NC treatment. Therefore, this study supports the administration of NC effectively ameliorated CPM-induced neurotoxicity in experimental rats.

Hepatoprotective and Antioxidant Effects of Nanopiperine against Cypermethrin via Mitigation of Oxidative Stress, Inflammations and Gene Expression Using qRT-PCR

“…Given these circumstances, piperine emerges as a promising therapeutic agent to counter liver toxicity. Previous studies have indicated that the toxicity mediated by Cyp results in an elevated concentration of ROS within cells, culminating in oxidative stress [29].…”

“…DNA fragmentation patterns serve as a reliable metric with which to evaluate apoptosis [29]. In cell death, endonucleases and proteolytic enzymes fragmented DNA and the chromatin into a smear-like pattern [42].…”

“…Lipid peroxidation was assayed in tissue homogenate using the methodology of Hussain et al [46]. GSH estimation by Ashfaq et al [29] was performed using SSA (4%) in a 1:1 ratio with a sample to assess the GSH. The solution combination was centrifuged for 15 min at 3000 rpm after being stored at 4 • C for an hour in order to separate the supernatant.…”