AMELIORATIVE ACTION OF SYNTHETIC AND HERBAL ANTIOXIDANTS ON LEAD INDUCED HEPATOTOXICITY: AN IN VITRO STUDY
Abstract
ABSTRACT
Objective: A lead is one of the most hazardous and persistent environmental toxicants of global concern today. The lead has propensity to act as a
potent mammalian systemic toxicant. Therefore, investigation of effective ameliorative techniques against lead toxicity through proper exploration of
molecular mechanisms is the main objective of the current study.
Methods: Present in vitro study deals with the investigation of ameliorative effect of specific synthetic antioxidants in a mixture especially,
N-acetyl cysteine (5.5 mM/kg/day), ascorbic acid (200 mg/kg/day), tocopheryl acetate (160 mg/kg/day), and thiamine (30 mg/kg/day) as novel
combinational therapy approach as well as Bacopa monnieri (10 mg/kg/day) as herbal antioxidant therapy against lead induced hepatotoxicity.
The current synergistic study involves culturing of goat liver in Dulbecco's Modified Eagle Medium:F12 (1:1 mixture) culture media containing
1 ppm lead acetate along with co-administration of selective antioxidants at prescribed dosage for 6 hrs. Selective biochemical parameters such
as lipid peroxidation (LPO), protein levels, alkaline phosphatase (ALPase), acid phosphatase (ACPase), succinate dehydrogenase (SDH), adenosine
triphosphatase (ATPase), and superoxide dismutase (SOD) activities were analyzed and observed for protection against lead intoxication.
Results: Results indicate significant alterations in all biochemical parameters studied in lead exposed cultures as compared to control. Total and
soluble proteins, ALPase, SDH, and ATPase showed significant reduction while LPO, ACPase, and SOD activities increased significantly in lead exposed
cultures as compared to control. The results also emphasized that simultaneous administration of prescribed antioxidants and lead in cultures
manifested maintenance of all biochemical parameters studied nearest to control group.
Conclusion: Synthetic and herbal antioxidants therapy have protective role against lead induced hepatotoxicity.
Keywords: Lead toxicity, Synthetic antioxidants, Herbal antioxidant, Bacopa monnieri extract, Hepatotoxicity, Oxidative stress, Plumbism,
Hepatoprotective activity, Lipid peroxidation, Superoxide dismutase.
Downloads
References
REFERENCES
ATSDR. The Nature and Extent of Lead Poisoning in Children in the
United States: A Report to Congress. DHHS Report No. 99-2966.
Atlanta: US Department of Health and Human Services; 2001.
Garza A, Vega R, Soto E. Cellular mechanisms of lead neurotoxicity.
Med Sci Monit 2006;12(3):RA57-65.
Sajitha GR, Jose R, Andrews A, Ajantha KG, Augustine P, Augusti KT.
Garlic oil and Vitamin E prevent the adverse effects of lead acetate and
ethanol separately as well as in combination in the drinking water of
rats. Indian J Clin Biochem 2010;25(3):280-8.
Khan MS, Mostafa MS, Hossain MA, Sayed MA. Effect of garlic
and Vitamin B complex in lead acetate induced toxicities in mice.
Bangladesh J Vet Med 2008;6(2):203-10.
Grant LD. Lead and compoundsâ€. In: Lippmann M, editor.
Environmental Toxicants: Human Exposures and Their Health Effects.
ed. Chichester: Wiley-Interscience; 2009.
Flora SJ, Flora G, Saxena G. Environmental occurrence, health effects
rd
and management of lead poisoning. In: Cascas SB, Sordo J, editors.
Lead Chemistry, Analytical Aspects, Environmental Impacts and
Health Effects. Netherlands: Elsevier Publication; 2006. p. 158-228.
Shukla R, Dietrich KN, Bornschein RL, Berger O, Hammond PB. Lead
exposure and growth in the early preschool child: A follow-up report
from the Cincinnati Lead Study. Pediatrics 1991;88(5):886-92.
Bressler J, Kim KA, Chakraborti T, Goldstein G. Molecular mechanisms
of lead neurotoxicity. Neurochem Res 1999;24(4):595-600.
Lanphear BP, Dietrich K, Auinger P, Cox C. Cognitive deficits
associated with blood lead concentrations <10 microg/dL in US
children and adolescents. Public Health Rep 2000;115(6):521-9.
Khalil-Manesh F, Gonick HC, Weiler EW, Prins B, Weber MA,
Purdy RE. Lead-induced hypertension: Possible role of endothelial
factors. Am J Hypertens 1993;6(9):723-9.
Diamond GL. Risk assessment of nephrotoxic metals. In: Tarloff J,
Lash L, editors. The Toxicology of Kidney. London: CRC Press; 2005.
p. 1099-132.
Shivaprasad R, Nagaraj M, Varalakshmi P. Combined efficacies of
lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid
peroxidation in rat liver. J Nutr Biochem 2004;15:18-23.
Patra RC, Swarup D, Dwivedi SK. Antioxidant effects of alpha
tocopherol, ascorbic acid and L-methionine on lead induced oxidative
stress to the liver, kidney and brain in rats. Toxicology 2001;162(2):81-8.
Ronis MJ, Badger TM, Shema SJ, Roberson PK, Templer L, Ringer D,
et al. Endocrine mechanisms underlying the growth effects of
developmental lead exposure in the rat. J Toxicol Environ Health A
;54:101-20.
Winder C. Lead, reproduction and development. Neurotoxicology
;14(2-3):303-17.
Lancranjan I, Popescu HI, GAvanescu O, Klepsch I, Serbanescu M.
Reproductive ability of workmen occupationally exposed to lead. Arch
Environ Health 1975;30(8):396-401.
Ercal N, Neal R, Treeratphan P, Lutz PM, Hammond TC, Dennery PA,
et al. A role for oxidative stress in suppressing serum immunoglobulin
levels in lead-exposed Fisher 344 rats. Arch Environ Contam Toxicol
;39:251-6.
Ahmed M, Siddiqui MK. Low level lead exposure and oxidative stress:
Current opinions. J Clin Chim Acta 2007;383:57-64.
Sidhu P, Nehru B. Lead intoxication: Histological and oxidative
damage in rat cerebrum and cerebellum. J Trace Elem Exp Med
;17(1):45-53.
Mudipalli A. Lead hepatotoxicity & potential health effects. Indian J
Med Res 2007;126(6):518-27.
Meyer SA, Kulkarni AP. Hepatotoxicity. In: Introduction to Biochemical
Toxicology. 3
ed. New York: John Wiley and Sons; 2001. p. 487.
Zmudski J, Bratton GR, Womac C, Rowe L. Lead poisoning in cattle:
rd
Reassessment of the minimum toxic oral dose. Bull Environ Contam
Toxicol 1983;30(4):435-41.
Aziz FM, Maulood IM, Chawsheen MA. Effects of melatonin,
Vitamin C and Vitamin E alone or in combination on lead-induced
injury in liver and kidney org of rats. IOSR J Pharm 2012;2(5):13-8.
Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions.
Free Radic Biol Med 1995;18(2):321-36.
Sipos P, Szentmihalyi K, Feher E, Abaza M, Szilagyi M, Blazovics A.
Some effects of lead contamination on liver and gallbladder bile. Acta
Biol Szeged 2003;47(1-4):139-42.
Jevtovic-Stoimenov T, Kocic G, Pavlovic D, Stajanovic I, Cvetkovic T,
Sokolovic D. Effects of captrol on membrance-associated enzymes
in lead induced hepatotoxicity in rats. Acta Fac Med Naiss
;20(3):183-8.
Annabi Berrahal A, Nehdi A, Hajjaji N, Gharbi N, El-Fazâa S.
Antioxidant enzymes activities and bilirubin level in adult rat treated
with lead. C R Biol 2007;330(8):581-8.
Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative
stress. Part -1. Mechanisms involved in metal-induced oxidative
damage. Curr Top Med Chem 2001;1:529-39.
Patrick L. Lead toxicity part II: The role of free radical damage and
the use of antioxidants in the pathology and treatment of lead toxicity.
Altern Med Rev 2006;11(2):114-27.
Farmand F, Ehdaie A, Roberts CK, Sindhu RK. Lead-induced
dysregulation of superoxide dismutases, catalase, glutathione
peroxidase, and guanylate cyclase. Environ Res 2005;98(1):33-9.
Gurer H, Ercal N. Can antioxidants be beneficial in the treatment of
lead poisoning? Free Radic Biol Med 2000;29(10):927-45.
El-Sokkary GH, Abdel-Rahman GH, Kamel ES. Melatonin protects
against lead-induced hepatic and renal toxicity in male rats. Toxicology
;213(1-2):25-33.
Gurer H, Ozgunes H, Neal R, Spitz DR, Erçal N. Antioxidant effects
of N-acetylcysteine and succimer in red blood cells from lead-exposed
rats. Toxicology 1998;128(3):181-9.
Flora SJ. Nutritional components modify metal absorption, toxic
response and chelation therapy. J Nutr Environ Med 2002;12:53-67.
Gupta R, Flora SJ. Protective value of Aloe vera against some toxic
effects of arsenic in rats. Phytother Res. 2005;19(1):23-8.
Kapoor R, Srivastava S, Kakkar P. Bacopa monnieri modulates
antioxidant responses in brain and kidney of diabetic rats. Environ
Toxicol Pharmacol 2009;27(1):62-9.
Cook NC, Samman S. Flavanoids-chemistry, metabolism, cardio
protective effects and dietary sources. Nutr Biochem 1996;7:66-76.
Pawar R, Gopalakrishnan C, Bhutani KK. Dammarane triterpene
saponin from Bacopa monniera as the superoxide inhibitor in
polymorphonuclear cells. Planta Med 2001;67(8):752-4.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues
by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351-8.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay
of superoxide dismutase. Indian J Biochem Biophys 1984;21(2):130-2.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement
with the Folin phenol reagent. J Biol Chem 1951;193(1):265-75.
Bessey OA, Lowry OH, Brock MJ. A method for the rapid determination
of alkaline phosphates with five cubic millimeters of serum. J Biol
Chem 1946;164:321-9.
Beatty CH, Basinger GM, Dully CC, Bocek RM. Comparison of red
and white voluntary skeletal muscle of several species of primates.
J Histochem Cytochem 1966;14:590-600.
Quinn PJ, White IG. Distribution of adenosinetriphosphatase activity in
ram and bull spermatozoa. J Reprod Fertil 1968;15(3):449-52.
Aykin-Burns N, Laegeler A, Kellogg G, Ercal N. Oxidative effects of
lead in young and adult Fisher 344 rats. Arch Environ Contam Toxicol
;44(3):417-20.
Yiin SJ, Lin TH. Lead-catalyzed peroxidation of essential unsaturated
fatty acid. Biol Trace Elem Res 1995;50(2):167-72.
Shafiq-ur-Rehman, Rehman S, Chandra O, Abdulla M. Evaluation of
malondialdehyde as an index of lead damage in rat brain homogenates.
Biometals 1995;8(4):275-9.
Ding Y, Gonick HC, Vaziri ND, Liang K, Wei L. Lead-induced
hypertension. III. Increased hydroxyl radical production. Am J
Hypertens 2001;14(4):169-73.
Subramaniam S, Shyama S, Shyamaladevi CS. Protective effect of
Vitamin E against CMF-induced damages in small intestinal brush
border membrane of rats. Indian J Pharmacol 1994;26:213-7.
Maiti PK, Kar A, Gupta P, Chaurasia SS. Loss of membrane integrity
and inhibition of type-I iodothyronine 5’-monodeiodinase activity
by fenvalerate in female mouse. Biochem Biophys Res Commun
;214(3):905-9.
Winterbourn CC. Superoxide as an intracellular radical sink. Free Radic
Biol Med 1993;14(1):85-90.
Kansal L, Sharma V, Sharma A, Lodi S and Sharma SH. Protective role
of Coriander extracts against lead nitrate induced oxidative stress and
tissue damage in the liver and kidney in male mice. International journal
of applied biology and pharmaceutical technology 2011;2(3):65-83.
Costa CA, Trivelato GC, Pinto AM, Bechara EJ. Correlation between
plasma 5-aminolevulinic acid concentrations and indicators of oxidative
stress in lead-exposed workers. Clin Chem 1997;43(7):1196-202.
Madiha M, Abdel-Kader, Abeer, Afify A, Amany, M. Hegazy. Roles of
N-acetylcysteine, methionine, Vitamin C and Vitamin E as antioxidants
against lead toxicity in rats. Aust J Basic Appl Sci 2011;5(5):1178-83.
Asian J Pharm Clin Res, Vol 9, Issue 2, 2016, 364-370
Shah and Jain
Soltaninejad K, Kebriaeezadeh A, Minaiee B, Ostad SN, Hosseini R,
Azizi E, et al. Biochemical and ultrastructural evidences for
toxicity of lead through free radicals in rat brain. Hum Exp Toxicol
;22(8):417-23.
Halliwell B, Gutteridge JM. Oxygen toxicity, oxygen radicals, transition
metals and disease. Biochem J 1984;219(8):1-14.
Shashi A, Thapar SP, Singh JP. Effects of fluoride administration on
organs of gastrointestinal tract-an exp. Study on rabbits-Effects on
tissue proteins. Fluoride 1987;20(3):183-8.
Esterbauer H. Lipid peroxidation products formation, Chemical
properties and biological activities. In: Poli G, Cheesman KH,
Dianzani MV, Slater TF, editors. Free Radical in Liver Injury. Oxford:
IRL Press Ltd.; 1986. p. 29-45.
Klockars M, Wegelius O. Lysosomal enzymes in regenerating rat liver.
Proc Soc Exp Biol Med 1969;131(1):218-22.
World Health Organization (WHO), IPCS International Programme
on Chemical Safety. Environmental Health Crieteria-36. Geneva:
United Nations Environment Programmme, The International Labour
Organization, and the World Health Organization; 1984. p. 1-136.
Harishekar MB. Studies on Alcohol-Lead Interactive Hepatotoxicity.
Ph.D. Thesis (Submitted), Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka. 2003. p. 77-9.
Hasan J, Vihko V, Hernberg S. Deficient red cell membrane/NaK/ATPase
in lead poisoning. Arch
Environ Health 1967;14(2):313-8.
Ercal N, Treeratphan P, Lutz P, Hammond TC, Matthews RH.
N-actylcysteine protects Chinese hamster ovary (CHO) cells from leadinduced
oxidative stress. Toxicology
;108(1-2):57-64.
Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action
of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl
radical, superoxide, and hypochlorous acid. Free Radic Biol Med
;6(6):593-7.
Mahaffey KR. Nutrition and lead: Strategies for public health. Environ
Health Perspect 1995;103 Suppl 6:191-6.
Chan AC. Partners in defense, vitamin E and vitamin C. Can J Physiol
Pharmacol 1993;71(9):725-31.
Leung HW, Vang MJ, Mavis RD. The cooperative interaction between
Vitamin E and Vitamin C in suppression of peroxidation of membrane
phospholipids. Biochim Biophys Acta 1981;664(2):266-72.
Chaurasia SS and Kar A. Protective effects of vitamin E against lead
induced deterioration of membrane associated type-I iodothyronine
’-monodeiodinase activity in male mice. Toxicology 124:203-09.
Ghazaly KS. Influences of thiamin on lead intoxication, lead deposition
in tissues and lead hematological responses of Tilapia zillii. Comp
Biochem Physiol C 1991;100(3):417-21.
Senapati SK, Dey S, Dwivedi SK, Patra RC, Swarup D. Effect of
thiamine hydrochloride on lead induced lipid peroxidation in rat liver
and kidney. Vet Hum Toxicol 2000;42(4):236-7.
Jung IL, Kim IG. Thiamine protects against paraquat-induced damage:
Scavenging activity of reactive oxygen species. Environ Toxicol
Pharmacol 2003;15(2):19-26.
Anna G, Wiglo S. Antioxidant activity of water soluble Vitamins in
TEAC (trolox equivalent antioxidant capacity) and the FRAP (ferric
reducing antioxidant power) assays. Food Chem 2006;96:131-6.
Tripathi YB, Chaurasia S, Tripathi E, Upadhyay A, Dubey GP. Bacopa
monniera Linn. as an antioxidant: Mechanism of action. Indian J Exp
Biol 1996;34(6):523-6.
Bhattacharya SK, Kumar A, Ghosal S. Effect of Bacopa monniera on
animal models of Alzheimer disease and perturbed central cholinergic
markers of congnition in rats. In: Siva Sankar DV, editor. Molecular
Aspects of Asian medicines. New York: PJD Publications; 2000a.
Russo A, Izzo AA, Borrelli F, Renis M, Vanella A. Free radical
scavenging capacity and protective effect of Bacopa monniera L. on
DNA damage. Phytother Res 2003;17(8):870-5.
Jyoti A, Sharma D. Neuroprotective role of Bacopa monniera extract
against aluminium-induced oxidative stress in the hippocampus of rat
brain. Neurotoxicology 2006;27:451-7.
Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J.
Chronic effects of Brahmi (Bacopa monnieri) on human memory.
Neuropsychopharmacology 2002;27:279-81.
Sumathi T, Nongbri A. Hepatoprotective effect of Bacoside-A,
A major constituent of Bacopa monniera Linn. Phytomedicine
;15(10):901-5.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.