Non-permitted food colorants induced neurotoxicity in cerebellum of rat brain.

Food colorants are important food additives that not only enhance the appearance of food but also appetite. These can be obtained from natural and synthetic sources, but synthetic sources are more popular, efficient, and potential. Non-permitted food colorants (NPFCs) are banned, but their injudicious use in developing countries associated with various adverse health effects. They have potentially toxic effects on the body organs like the brain, liver, kidney, spleen, gut, etc. In view of their toxicity pattern, the present study aims to investigate the effect of three NPFCs (MY: Metanil yellow; MG: Malachite green; SIII: Sudan III) on oxidative stress, mitochondrial complexes, neurochemicals, and histological changes in the cerebellum of rats. Rats treated with MY (430 mg/kg), MG (13.75 mg/kg), SIII (250 mg/kg), and their mixtures (YGR) (MY 143.33 + MG 4.52 + SIII 83.33 mg/kg) p.o. for 60 days showed a significant increase in lipid peroxidation and decreased level of reduced glutathione, superoxide dismutase, and catalase activity as compared to controls. An increase in the activity of acetylcholinesterase (AChE) and a significant decrease in the activity of monoamine oxidase-B (MAO-B) and mitochondrial complex I and II was also observed in NPFCs treated rats as compared to controls. Further, the histological study also revealed the loss of Purkinje neurons in the cerebellum of the rat brain. The results of the present study indicate that NPFCs exposure to rats enhances oxidative stress and alters the activity of neurochemicals and mitochondrial complexes which could further lead to neuronal loss and behavioral dysfunctions.

Neuroprotective effects of mitochondria-targeted curcumin against rotenone-induced oxidative damage in cerebellum of mice.

The present study investigated the protective effect of curcumin and mitochondrial-targeted curcumin (MTC) in rotenone-induced cerebellar toxicity in mice. Treatment of rotenone in mice significantly shortened the stride length for both forelimb and hind-limb and increased fore-paws and hind-limb base width. Co-treatment of curcumin and MTC with rotenone improved the walking pattern. A significant increase in lipid peroxidation, nitric oxide and decreased activity of AChE, reduced glutathione, superoxide dismutase and catalase were observed in rotenone-treated mice while co-treatment of curcumin and MTC with rotenone significantly increased AChE activity and protected against rotenone-induced oxidative damage. Rotenone exposed mice showed irregular, damaged Purkinje cells and perineuronal vacuolation while co-treatment of curcumin and MTC with rotenone protected against rotenone-induced cellular damage in these cells. The result exhibits that both curcumin and MTC showed protective effects against rotenone-induced cerebellar toxicity in mice and MTC is more effective than curcumin.

Cholinesterase inhibition and its association with hematological, biochemical and oxidative stress markers in chronic pesticide exposed agriculture workers.

The present study investigated the pesticide induced adverse health effects, hematological and biochemical alterations among agriculture workers. A cross sectional study of 51 agriculture workers and 54 unexposed subjects was carried out to evaluate hematological and biochemical alterations in blood. Pesticide exposed individuals were reported adverse clinical outcomes, including tingling, muscle pain, headache, skin disease, etc. A significant alterations in the level of hematological parameters, liver and renal dysfunctions markers and lipid profile suggested hematological, hepatic and renal dysfunctions. A significant decrease in the activity of acetylcholinesterase, reduced glutathione, superoxide dismutase, catalase and increased level of lipid peroxidation was also observed in these agriculture workers. Correlation coefficient analysis showed a positive correlation of chronic exposure with most of the hematological and biochemical parameters. The results demonstrate that the chronic exposure of pesticides cause reduction in the acetylcholinesterase activity and enhanced the risk of adverse clinical outcomes in agriculture workers.

Neurochemical and Behavioral Dysfunctions in Pesticide Exposed Farm Workers: A Clinical Outcome.

The problem of pesticides is not new and its exposure to human due to indiscriminate use is largely associated with the health related problems including neurotoxicological alterations. High levels of pesticide residues and their metabolites in the dietary constituents, food materials, maternal blood, cord blood, placenta breast milk have been reported and linked to alterations in birth weight, crown heel length, head circumference, mid-arm circumference and ponderal index of the neonates. Epidemiological studies have suggested that exposure of pesticide to human could be a significant risk factor for neurological disorders, including Parkinson's disease, Alzheimer's disease and multiple sclerosis. Cholinergic and non-cholinergic dysfunctions in pesticide exposed population, especially in children have also been frequently reported in recent years. Developmental neurotoxicity is another concern in the area where pregnant are more prone towards its exposure and which results in the abnormalities in the fetus. In view of the increasing risk of human health through pesticide exposure, the present review has been focused on the studies pertaining to pesticide induced neurochemical alterations and associated behavioral abnormalities in farm workers which could establish a possible link between the its exposure and associated health hazards.

Process development for the total synthesis of the novel drug metabolite Carboxy toremifene as a standard reference material along with characterization and purity assessment for the Antidoping quality Control Purposes.

Tamoxifen and toremifene are two selective estrogen receptor modulators (SERMs) commonly used to treat breast cancer in women. Toremifene is well-known as a triphenylethylene derivative. Carboxy toremifene is a common metabolite of toremifene and tamoxifen. Since 2005, the World Anti-Doping Agency (WADA) has banned the SERMs category during in and out of competition. These substances are in the S4 category in the WADA prohibited list as "agents with anti-oestrogenic activity." However, there is no commercially accessible carboxy toremifene reference material in the market. This research highlights the novel synthetic procedure, the development of a carboxy toremifene HPLC method, and validation, along with detailed characterization using advanced analytical techniques using 1 H NMR, HRMS, FT-IR-ATR and UV-visible spectroscopy. RP-HPLC-DAD method was developed and validated to assess the purity of carboxy toremifene. Developed reference material has shown 100% purity. Therefore, we recommend that this synthesized carboxy toremifene may be used as reference material to strengthen the WADA-accredited lab to maintain a clean sports mission during sports competitions.

Synthesis, characterization and efficacy of mitochondrial targeted delivery of TPP-curcumin in rotenone-induced toxicity.

BACKGROUND: Mitochondrial impairments due to free radicals are implicated in a wide range of neurotoxicological alterations. Curcumin, an active ingredient of turmeric has shown protective efficacy against oxidative damage due to its strong antioxidant potential, but its efficiency is restricted due to low bioavailability in the mitochondria. In view of this, we have synthesized mitochondria-targeted curcumin (MTC) with an aim to investigate its efficacy against rotenone-induced oxidative damage in mice and isolated mitochondria. METHODS: MTC was synthesized by attaching the triphenylphosphonium cation (TPP) as a cationic carrier to the curcumin to assess its protective efficacy in rotenone-induced in-vitro and in-vivo toxicity in mice. RESULTS: In-vitro treatment of rotenone in isolated mitochondria caused a significant increase in lipid peroxidation (2.74 fold, 3.62 fold), protein carbonyl contents (2.62 fold, 1.81 fold), and decrease in levels of reduced glutathione (2.02 fold, 1.70 fold) as compared to control. Pre-treatment of curcumin and MTC along with rotenone in the isolated mitochondria significantly reduce the oxidative stress as compared to those treated with rotenone alone. Rotenone treatment in mice significantly increased lipid peroxidation (2.02 fold) and decreased the levels of reduced glutathione (2.99 fold), superoxide dismutase (2.09 fold) and catalase (3.60 fold) in the liver as compared to controls. Co-treatment of curcumin and MTC along with rotenone significantly reduced lipid peroxidation (1.26 fold, 1.76 fold) and increased the levels of reduced glutathione (1.60 fold, 2.43 fold), superoxide dismutase (1.45 fold, 1.99 fold) and catalase (2.32 fold, 2.90 fold) as compared to those treated with rotenone alone. CONCLUSION: The results of the present study indicate that the protective efficacy of MTC against rotenone-induced oxidative damage was more promising than curcumin in both in-vitro and in-vivo system which indicates the enhanced bioavailability of MTC. Graphical abstract Effect of mitochondrial targeted delivery of TPP-curcumin in rotenone-induced toxicity.