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

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

Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-) induced diabetes mellitus and its complication in central nervous system (CNS). Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65 mg/kg body weight). Three days after STZ injection, HP was given (50 mg/kg b.wt. orally) once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model

Cardioprotective Effects of Nano-Piperine Against Cypermethrin Toxicity Through Oxidative Stress, Histopathological and Immunohistochemical Studies in Male Wistar Rats

Background: Cypermethrin (Cyp) is a synthetic derivative of pyrethroids, implicated in various organ toxicity. This study investigated the potential cardio-protective activity of nano-piperine (NP) against Cyp toxicity in adult Wister male rats. Methods: All animals in groups II, III, IV, and V were subjected to Cyp (50 mg/kg) for 15 days. After 1 h of receiving the Cyp dose, 3 doses of NP (125, 250, and 500 µg/kg/day) were administered to groups III, IV, and V, respectively, for 10 days. In Group VI, a dose of 500 µg/kg NP alone was given orally daily for 10 days. Result: The toxic effects were evaluated by an increase in serum cardiac injury biomarkers (lactate dehydrogenase, cardiac troponin I, creatine kinase-myoglobin binding, tissue lipid peroxidation, a decrease in antioxidative activity, such as glutathione, superoxide dismutase [SOD] and catalase, and upregulation of interleukins [interleukin 1β, interleukin 6]). Immunohistochemistry studies of proteins (nuclear factor-κB [NF-kB], apoptotic protease activating factor-1 [Apaf-1], 4-hydroxynonenal [4-HNE] and Bax) showed enhanced expression, and histopathological examination revealed myolysis, loss of striation and hemorrhages indicating heart toxicity in the animals. Administration of NP significantly ameliorated all the changes caused by Cyp, such as a decrease in the levels of serum cardiac injury markers, an increase of antioxidative parameters, decrease in expression of inflammatory cytokines and NF-kB, Apaf-1, 4-HNE, and Bax, as shown by immunohistochemistry studies. Furthermore, all the histopathological changes were reduced to near the values of the control. Conclusion: Collectively our findings indicated that NP could be a potent nutraceutical exhibiting cardioprotective effects against Cyp-induced cardiotoxicity in rats. </jats:p