curcumin and Cadmium-Poisoning

Heavy metal neurotoxicity is one of the major challenges in today's era due to the large scale and widespread mechanisation of the production. However, the causative factors responsible for neurotoxicity are neither known nor do we have the availability of therapeutic approaches to deal with it. One of the major causative agents of neurotoxicity is a non-essential transition heavy metal, Cadmium (Cd), that reaches the central nervous system (CNS) through the nasal mucosa and olfactory pathway causing adverse structural and functional effects. In this study, we explored the neuroprotective efficacy of plant derived Curcumin which is reported to have pleiotropic biological activity including anti-oxidant, anti-inflammatory, anti-apoptotic, anti-carcinogenic and anti-angiogenic effects. Four different concentrations of curcumin (20, 40, 80 and 160 mg/kg of the body weight) were used to assess the behavioural, biochemical, hippocampal proteins (BDNF, CREB, DCX and Synapsin II) and histological changes in Swiss Albino mice that were pre-treated with Cd (2.5 mg/kg). The findings showed that Cd exposure led to the behavioural impairment through oxidative stress, reduction of hippocampal neurogenesis associated proteins, and degeneration of CA3 and cortical neurons. However, treatment of different curcumin concentrations had effectively restored the behavioural changes in Cd-exposed mice through regulation of oxidative stress and up-regulation of hippocampal proteins in a dose-dependent manner. Significantly, a dose of 160 mg/kg body weight was found to be glaringly effective. From this study, we infer that curcumin reverses the adverse effects of neurotoxicity induced by Cd and promotes neurogenesis.

Topics: Animals; Anxiety; Behavior, Animal; Brain-Derived Neurotrophic Factor; CA3 Region, Hippocampal; Cadmium Poisoning; Cerebral Cortex; Curcumin; Cyclic AMP Response Element-Binding Protein; Doublecortin Protein; Hippocampus; Maze Learning; Mice; Neurogenesis; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Psychomotor Performance; Signal Transduction

This study investigated the protective effect of curcumin on memory loss and on the alteration of acetylcholinesterase and ectonucleotidases activities in rats exposed chronically to cadmium (Cd). Rats received Cd (1 mg/kg) and curcumin (30, 60, or 90 mg/kg) by oral gavage 5 days a week for 3 months. The animals were divided into eight groups: vehicle (saline/oil), saline/curcumin 30 mg/kg, saline/curcumin 60 mg/kg, saline/curcumin 90 mg/kg, Cd/oil, Cd/curcumin 30 mg/kg, Cd/curcumin 60 mg/kg, and Cd/curcumin 90 mg/kg. Curcumin prevented the decrease in the step-down latency induced by Cd. In cerebral cortex synaptosomes, Cd-exposed rats showed an increase in acetylcholinesterase and NTPDase (ATP and ADP as substrates) activities and a decrease in the 5'-nucleotidase activity. Curcumin was not able to prevent the effect of Cd on acetylcholinesterase activity, but it prevented the effects caused by Cd on NTPDase (ATP and ADP as substrate) and 5'-nucleotidase activities. Increased acetylcholinesterase activity was observed in different brain structures, whole blood and lymphocytes of the Cd-treated group. In addition, Cd increased lipid peroxidation in different brain structures. Higher doses of curcumin were more effective in preventing these effects. These findings show that curcumin prevented the Cd-mediated memory impairment, demonstrating that this compound has a neuroprotective role and is capable of modulating acetylcholinesterase, NTPDase, and 5'-nucleotidase activities. Finally, it highlights the possibility of using curcumin as an adjuvant against toxicological conditions involving Cd exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 70-83, 2017.

Topics: Animals; Avoidance Learning; Cadmium Poisoning; Curcumin; Dose-Response Relationship, Drug; Electroshock; Lipid Peroxidation; Male; Memory Disorders; Motor Activity; Parasympathetic Nervous System; Rats; Rats, Wistar; Receptors, Purinergic; Signal Transduction; Synaptosomes

In the present work, protective effect of tetrahydrocurcumin (THC) against oxidative damages in cadmium (Cd)-induced toxicity in rats was evaluated. Cd is an important environmental and industrial toxicant that affects almost all the organs, especially liver. Liver is the major organ responsible for the metabolism and the primary target for many toxic chemicals and drugs. Effect of THC, the curcumin-derived polyphenolic compound on Cd-induced oxidative stress and hepatic damage was evaluated using male albino Wistar rats. In Cd-administered rats (5 mg/kg body weight (b.w.), orally for 4 weeks), activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) were significantly increased in serum with the elevated level of bilirubin. Red blood cells (RBC), haemoglobin contents and haematocrit values were also significantly decreased in Cd-treated rats. In addition, the levels of lipid peroxidation markers like thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHP), protein carbonyl contents (PCC) and conjugated dienes (CD) were significantly increased followed by the significant decrease in the levels of reduced glutathione (GSH), total sulphydryl groups (TSH), ascorbic acid (vitamin C) and vitamin E in liver of Cd-administered rats. Oral administration of THC (20, 40 and 80 mg/kg b.w.) followed by Cd for 4 weeks showed a significant restoration of the above changes to near normal. Histopathological changes observed in Cd intoxicated hepatic tissues were minimized on treatment with THC. This study suggests that THC at the dose of 80 mg/kg b.w. effectively subdues the Cd-induced toxicity and controls the free radical-induced liver damage in rats.

Topics: Animals; Cadmium; Cadmium Poisoning; Curcumin; Liver; Male; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar

The present study was designed to investigate the effect of CdCl₂-polluted drinking water (40 mg CdCl₂/L) on the level of TNF-α and IL-6, as well as oxidative status biomarkers in plasma of rats. The possible protective effect of oral administration of curcumin (50 mg/kg body weight/day) was assessed. Results illustrated that Cd exposure significantly elevated the plasma levels of TNF-α and IL-6 (p<0.001) as compared to normal rats. Also, Cd administration resulted in a significant elevation in the lipid peroxidation and markedly reduction in the activities of SOD and catalase as well as the level of glutathione and total antioxidant capacity in plasma. The co-treatment of Cd with curcumin significantly reduced the levels of TNF-α and IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Negative correlation between IL-6 or TNF-α was and the plasma activities of catalase, SOD and the level of total antioxidant capacity were found in rats exposed to Cd.. Cadmium toxicity induced the release of TNF-α and IL-6 which is associated with systemic oxidative stress. This may be involved in the mechanism of the Cd toxicity. On the other hand, the findings suggest the curative action of curcumin against Cd toxicity.

Topics: Animals; Antioxidants; Biomarkers; Cadmium; Cadmium Chloride; Cadmium Poisoning; Curcumin; Glutathione; Immune System; Interleukin-6; Lipid Peroxidation; Male; Oxidation-Reduction; Oxidative Stress; Oxidoreductases; Rats; Tumor Necrosis Factor-alpha; Up-Regulation; Water Pollutants, Chemical; Weight Loss