Strategies to Combat Arsenic Calamity in West Bengal, India as Madhum umita Roy , Sut Sutapa Muk ukherjee, Jaydip Jaydip Bisw Biswas Ch Chittaranj njan n Nationa nal Ca Canc ncer Ins nstitut ute, Kolkata, INDIA. Cancer caused by Arsenic: Kolkata, INDIA • Skin • Liver • Lung • Kidney • Bladder Objectives of the field trial To compare and establish the efficacy of curcumin-piperine formulation over curcumin alone in reversal of DNA damage, induction of antioxidant enzymes and acceleration of repair potential in a population chronically exposed to arsenic in ground water. Demographic details of village in Chakdah Block of Nadia district in West Bengal, India Area No. of volunteers As level ( µ g/l) Curcumin level ( µ g/ml) ♂ ♀ in water in blood Cur Cur+Pip Chakdah Block 100 78 250±12 14.00±1.73 2.59±0.38 2.68±0.46 Criteria for selection of volunteers Inclusion criteria Exclusion criteria 1. Age 25-55 yrs 3. No disease or external 1. High blood pressure & blood sugar 2. Non-smokers manifestations 2. Skin or chronic disease
DNA Damage Con Cur Con Cur Double strand DNA % Comet Tail Moment ( µ m) Cur + Pip Plcbo Cur + Pip Plcbo 8 80 6 60 4 40 2 20 0 0 1 2 3 4 5 6 1 2 3 4 5 6 Time in months Absorbance at 535 nm Cur Cur+Pip Curcumin level in blood plasma ( µ g/ml) 0.012 1 month 2 months 3 months ROS 0.008 Curcumin 2.45±0.16 2.67±0.32 2.67±0.34 Cur+Pip 2.65±0.04 2.56±0.22 2.61±0.43 0.004 Antioxidant Enzyme Activity 0 SOD activity / mg of 0 1 2 3 Catalase activity / 0.006 0.018 n moles of MDA / mg protein mg of protein Time in months SOD Catalase Cur Cur+Pip protein 0.004 0.012 0.09 0.002 0.006 L P O 0.06 0 0 0 1 2 3 0 1 2 3 Specific activity of GPX / Specific activity of GR / GST activity (nmoles / 0.03 500 4 4 GR mg of protein GPX GST mg of protein 0 min / ml) 0 1 2 3 250 2 2 Time in months 0 0 0 0 1 2 3 0 1 2 3 0 1 2 3 Time in months
Highlights Cur Cur+Pip Repair % 80 Curcumin in combination with piperine 60 significantly reduces the extent of DNA damage in 40 a population exposed to arsenic in ground water in 20 West Bengal, India. Antioxidant enzymes have 0 been elevated by curcumin and introduction of 1 2 3 4 5 6 Time in months piperine with curcumin further increases the level of these enzymes. Repair of DNA damage also 116 kDa PARP I plays a crucial role in carcinogenesis and arsenic inhibits DNA repair in individuals. Curcumin Ligase III 103 kDa induces repair enzymes, at protein and at genetic 85 kDa XRCC I level and inclusion of piperine with curcumin further enhances the repair process. Topo II β 180 kDa DNA β pol 43 kDa 233 bp PARP I Ligase III 150 bp XRCC I 236 bp Topo II β 179 bp DNA β pol 204 bp Curcumin-piperine formulation is quite effective in reducing the DNA damage, thereby blocking the initiation stage of carcinogenesis. Furthermore, the phase II detoxification enzymes are efficiently induced along with accelerated DNA repair process upon intake of curcumin-piperine capsules. Therefore inclusion of piperine along with curcumin in a population in the arsenic affected area may help to prevent DNA damage, therefore the onset of carcinogenesis and this may have great influence in cancer control.
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