Curcumin Attenuates Aluminum-Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Brain

Abstract

Aluminum is neurotoxic both in animals and human beings primarily because of its interference with biological enzymes in key mechanisms of metabolic pathways. Mitochondrial dysfunction is one such mechanism that has been implicated in the pathogenesis of neurodegenerative diseases like Alzheimer's disease. Aluminum toxicity is very closely related to Alzheimer's disease. We evaluated the potentials of curcumin, a known cytoprotectant, against neurotoxic consequences of aluminum that acts through a wide range of mechanisms. Curcumin has been reported to be an antioxidant, and it is this property that is widely held to be responsible for its protective effects in tissue. Aluminum was administered by oral gavage at a dose level of 100 mg/kg body wt/day for a period of 8 weeks. Curcumin was administered in conjunction with aluminum at a dose of 50 mg/kg of body wt i.p. for a period of 8 weeks on alternate days. The effects of different treatments were studied on oxidative phosphorylation and reduced glutathione of different regions of rat brain. The study indicates reduced activity of NADH dehydrogenase (complex I), succinic dehydrogenase (complex II), and cytochrome oxidize (Complex IV) in all the three regions of rat brain, i.e., cerebral cortex, mid brain, and cerebellum. Curcumin supplementation to aluminum-treated rats was able to normalize significantly the activities of all the three mitochondrial complexes as well as reduced glutathione content in all the three regions of brain which were altered following aluminum treatment. We conclude that curcumin, by attenuating oxidative stress, as evident by hypoxia in histological observations and mitochondrial dysfunction holds a promise as an agent that can potentially reduce aluminum-induced adverse effects in brain.

Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

“…• Reduced the aluminum-induced inflammatory response as indicated by down-regulation of NF-kB and TNF-a in glial cells (Sood et al, 2011).…”

“…Curcumin also protects against the toxic effects of copper overload (Wan et al, 2007), dextran sulfate sodium (Arafa et al, 2009), p-dioxin (Ciftci et al, 2010) and aluminum (Sood et al, 2011) through down-modulation of TNF-a. A reduction in the production of iNOS mRNA was observed when BALB/c mouse peritoneal macrophages cultured ex vivo were treated with 1-20 mM curcumin (Chan et al, 1998); in vivo, two oral treatments of 0.5 mL of a 10 mM solution of curcumin (92 ng·g -1 bodyweight) reduced iNOS mRNA expression in the livers of LPS-injected mice by 50-70% (Chan et al, 1998).…”

Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin

“…The mitochondria are both a major source of reactive oxygen species (ROS) production as well as a major target for ROS-induced cellular injury. Toxic consequences of electron transport chain dysfunction may ensure mitochondrial damage including oxidation of mitochondrial DNA, proteins, and lipids, which may lead to the opening of mitochondrial permeability transition pore, an event that is linked to cell death in neuronal model systems (Sood et al 2011). A direct link between mitochondrial dysfunction and toxic manifestations of anticancer drugs has been established (Burgeiro et al 2011).…”

“…The use of both CMN and QR has been reported as a therapeutic agent to mitigate various kinds of toxicity including cardiotoxicity (Matouk et al 2013;Swamy et al 2012), nephrotoxicity (Ciftci et al 2012;Nabavi et al 2012), hepatotoxicity (Waseem and Parvez 2013;Sekaran et al 2012), and neurotoxicity (Haleagrahara et al 2013;Yadav et al 2011). Pretreatment with CMN and QR was found to modulate mitochondrial dysfunction in rodents, and its property as an antioxidant is widely held to be responsible for its protective effects in the mitochondria (Carrasco-Pozo et al 2012;Sood et al 2011). The compound has been described to possess a variety of pharmacological and biological activities including anti-inflammatory (Dai et al 2013;Wang et al 2012), antimicrobial (Kallio et al 2012), antioxidant (Waseem and Parvez 2013;Tang et al 2012), and anticancer activities (Youn et al 2013;Sarkar et al 2010).…”

Protective Effect of Dietary Curcumin and Capsaicin on LPS-Induced Inflammation in Mice

“…[10][11][12] Effective in protecting heat induced oxidant stress, 13 chromiuminduced renal damage, 14 cisplatin-induced hepatotoxicity, 15 aluminum-induced mitochondrial dysfunction in vivo. 16 Whereas, capsaicin, a component of Capsicum annum exerts various pharmacological properties, including antioxidant, anti-inflammatory and anti-epileptic effects. 17,18,19 In vivo reports have established that capsaicin inhibits cisplatininduced nephrotoxicity, Lipid peroxidation, renal injury, oxidative stress and inflammation, 20,21 cecal ligation and puncture (CLP) induced systemic inflammatory responses.…”