full issue - Association of Biotechnology and Pharmacy
full issue - Association of Biotechnology and Pharmacy
full issue - Association of Biotechnology and Pharmacy
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Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong>Vol. 5 (2) 1193-1205 April 2011. ISSN 0973-8916 (Print), 2230-7303 (Online)1201A generalised reduction in brain cholinergicfunction has been reported in Pb-treated rats.Exposure to Pb resulted in a decrease in the AChEactivity in cerebellum <strong>and</strong> hippocampus at variouspost natal time points (22). Neonatal exposure toPb altered the muscarinic receptor density (27)which account for the deficits in central cholinergicfunctions (28). The results <strong>of</strong> our present studyare in agreement with these findings.The alterations in AChE activity duringearly postnatal development could be related withthe fact that Pb crosses the blood brain barrierquite readily (29). The inhibitory effect <strong>of</strong> Pb onAChE activity also reflected in alterations in themotor activity (30, 5). The results <strong>of</strong> the presentstudy showed maximum alterations in AChEcontent in hippocampus <strong>of</strong> Pb-treated rats. Thecholinergic synapses are more in hippocampusas compared to cerebral cortex <strong>and</strong> cerebellum(31). AChE inhibition in this area leads tocognitive <strong>and</strong> non cognitive alterations as this isthe principle area for memory <strong>and</strong> cognition. Thefact that the hippocampus develops late (32) <strong>and</strong>sequester, Pb, primarily in the mossy fibrepathway (33) would put this structure at particularrisk for damage following early Pb-exposure.Since the cholinergic system isresponsible for the behavioral manifestations, anyalteration in the cholinergic system would bereflected in the behavior. In the present study,the observed alterations in cholinergic systemhave greatly influenced the open field behavior<strong>of</strong> rats exposed to Mn <strong>and</strong> Pb. The memory <strong>and</strong>spatial discrimination tasks in Morris water mazealso decreased suggesting the hippocampaldamage due to Pb+Mn exposure.Supplementation with Ca 2+ reversed the Pb<strong>and</strong> Mn induced inhibition in AChE activity. Thereversal <strong>of</strong> inhibition in the activity <strong>of</strong> AChE bysupplementation with Ca 2+ may be due tocompetition <strong>of</strong> these metals for similar bindingsites <strong>and</strong> reducing the availability <strong>of</strong> binding sitesfor Pb or Mn.Ca 2+ is a divalent cation just like Pb.Because the same transport mechanism isoperative for absorption <strong>of</strong> Pb <strong>and</strong> Ca 2+ from thegastrointestinal tract there is resulting competitiveinteraction between Pb <strong>and</strong> Ca 2+ (34). Studieshave shown that Pb has an inhibitory effect onthe peripheral nervous system through stimuluscoupled or Ca 2+ dependent release <strong>of</strong>acetylcholine (35) <strong>and</strong> this inhibitory effect <strong>of</strong> Pbat the neuromuscular junction <strong>and</strong> the ganglionwas similar to the effect <strong>of</strong> reducing theconcentration <strong>of</strong> Ca 2+ in bathing media <strong>of</strong> neuralpreparations; so it is not surprising that thisinhibitory effect <strong>of</strong> Pb can be overcome by theaddition <strong>of</strong> Ca 2+ . Absorption <strong>of</strong> Pb bygastrointestinal tract is inversely related to theamount <strong>of</strong> Ca 2+ present (36, 37). FurthermoreCa 2+ supplements had a protective effect bysignificantly reducing blood Pb levels in pregnantwomen whose diets were deficient in Ca 2+ (38,39). Ziegler et al., (40) observed an inverserelationship between dietary Ca 2+ <strong>and</strong> Pbretention <strong>and</strong> absorption in young infants.Pb+Mn-exposure exerted inhibitoryaction on the activity <strong>of</strong> enzymes Mg 2+ , <strong>and</strong>Na + K + ATPases in the developing brain. Heavymetals such as Pb can bind to a number <strong>of</strong> siteson proteins including imidazole, histodyl, carbonyl<strong>and</strong> especially sulfhydryl side chains (41). Heavymetals have great affinity for ATPase system <strong>and</strong>they interact with enzyme molecule resulting inthe inhibition (42). Pb has been reported to inhibitNa + K + ATPase <strong>of</strong> mammalian t<strong>issue</strong>s (43, 44) <strong>and</strong>also interferes with mitochondrial function <strong>and</strong>blocks the O 2uptake. Bhaumik <strong>and</strong> Raychudhari(45) reported that the inhibition <strong>of</strong> Na + K + ATPasemay be due to the flow <strong>of</strong> the Na + K + ions fromthe t<strong>issue</strong>s to the blood. The decrease in theMg 2+ ATPase activity might be due to lowoperation <strong>of</strong> oxidative pathway, resulting inCalcium protection against lead <strong>and</strong> manganese toxicity