Curative Effects of Dhatryadi ghrita Bioactive Extracts on Ethanol Withdrawal Syndrome in Wistar Rats

Rashmi    S.   Pal; Amrita       Mishra

doi:10.2174/1573407216666200226092924

Abstract

Background: Alcohol withdrawal syndrome leads to irritability, aggressiveness, body posture and motor abnormalities, sensory hyper reactivity and changes in various enzyme levels. Dhatryadi ghrita penetrates the blood-brain barrier to decrease the cravings for alcohol in this syndrome.

Objective: To evaluate the effect of alcoholic extract of Dhatryadi ghrita on alcohol withdrawal syndrome in Wistar rats.

Materials & Methods: A liquid diet with 7.2%, v/v ethanol was administered to the Wistar rats for 21 days. Control group animals received saline and normal diet. After alcohol withdrawal, rats were examined at 6th and 24th hour for anxiety and hyper locomotor activity as major withdrawal signs. Anxiety due to ethanol withdrawal was tested with the help of elevated plus maze, light and dark models. The hyper locomotor activity was assessed using Actophotometer. The hepatic enzymes level was determined with the help of the Bio-chemical Analyzer. ghrita extracts (100, 200,300 mg/kg, oral) were administered to different groups and diazepam as standard (2 mg/kg, i.p) was administered to the treatment group animals 30 minutes before alcohol withdrawal estimation. Drug treatment was administered 30 minutes before the second observation at the 24th hour.

Results: Findings from the present study revealed that Ghrita extract treatment at doses 100, 200 and 300 mg/kg, oral in ethanol-dependent rats had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats.

Conclusion: Dhatryadi extract acts effectively for the treatment of alcohol abstinence syndrome. The extract treatment has beneficial effects on ethanol withdrawal depressive-like behavior in rats.

Keywords: Dhatryadi ghrita, ethanol withdrawal syndrome, anxiety, hyperlocomotor activity, enzymes, benzodiazepines.

Graphical Abstract

[1] 
Weissman, M.M.; Myers, J.K. Clinical depression in alcoholism. Am. J. Psychiatry,  1980, 137(3), 372-373.
[http://dx.doi.org/10.1176/ajp.137.3.372] [PMID:  7356070] 
[2] 
Miguel-Hidalgo, J.J.; Rajkowska, G. Comparison of prefrontal cell pathology between depression and alcohol dependence. J. Psychiatr. Res.,  2003, 37(5), 411-420.
[http://dx.doi.org/10.1016/S0022-3956(03)00049-9] [PMID:  12849933] 
[3] 
Jesse, S.; Bråthen, G.; Ferrara, M.; Keindl, M.; Ben-Menachem, E.; Tanasescu, R.; Brodtkorb, E.; Hillbom, M.; Leone, M.A.; Ludolph, A.C. Alcohol withdrawal syndrome: Mechanisms, manifestations, and management. Acta Neurol. Scand.,  2017, 135(1), 4-16.
[http://dx.doi.org/10.1111/ane.12671] [PMID:  27586815] 
[4] 
Fiellin, D.A.; O’Connor, P.G.; Holmboe, E.S.; Horwitz, R.I. Risk for delirium tremens in patients with alcohol withdrawal syndrome. Subst. Abus.,  2002, 23(2), 83-94.
[http://dx.doi.org/10.1080/08897070209511478] [PMID:  12444353] 
[5] 
Dodd, P.R.; Beckmann, A.M.; Davidson, M.S.; Wilce, P.A. Glutamate-mediated transmission, alcohol, and alcoholism. Neurochem. Int.,  2000, 37(5-6), 509-533.
[http://dx.doi.org/10.1016/S0197-0186(00)00061-9] [PMID:  10871702] 
[6] 
Kumar, J.; Hapidin, H.; Get Bee, Y.T.; Ismail, Z. The effects of acute ethanol administration on ethanol withdrawal-induced anxiety-like syndrome in rats: A biochemical study. Alcohol,  2016, 50, 9-17.
[http://dx.doi.org/10.1016/j.alcohol.2015.10.001] [PMID:  26626323] 
[7] 
Schunck, R.V.A.; Macedo, I.C.; Laste, G.; de Souza, A.; Valle, M.T.C.; Salomón, J.L.O.; Nunes, E.A.; Campos, A.C.W.; Gnoatto, S.C.B.; Bergold, A.M.; Konrath, E.L.; Dallegrave, E.; Arbo, M.D.; Torres, I.L.S.; Leal, M.B. 
            Standardized 
            Passiflora incarnata
             L. extract reverts the analgesia induced by alcohol withdrawal in rats.
           Phytother. Res.,  2017, 31(8), 1199-1208.
[http://dx.doi.org/10.1002/ptr.5839] [PMID:  28568647] 
[8] 
Sachdeva, A.; Choudhary, M.; Chandra, M. Alcohol withdrawal syndrome: Benzodiazepines and beyond. J. Clin. Diagn. Res.,  2015, 9(9), 1-7.
[9] 
Roberts, A.J.; Heyser, C.J.; Cole, M.; Griffin, P.; Koob, G.F. Excessive ethanol drinking following a history of dependence: Animal model of allostasis. Neuropsychopharmacology,  2000, 22(6), 581-594.
[http://dx.doi.org/10.1016/S0893-133X(99)00167-0] [PMID:  10788758] 
[10] 
Besheer, J.; Lepoutre, V.; Hodge, C.W. Preclinical evaluation of riluzole: Assessments of ethanol self-administration and ethanol withdrawal symptoms. Alcohol. Clin. Exp. Res.,  2009, 33(8), 1460-1468.
[http://dx.doi.org/10.1111/j.1530-0277.2009.00976.x] [PMID:  19426166] 
[11] 
Sharma, L.; Sharma, A.; Gupta, G.L. Standardization of a polyherbal preparation (pol-6) for treatment of oxidative, inflammatory and immune disorders. Int. J. Pharm. Pharm. Sci.,  2016, 8(4), 129-134.
[12] 
Salottolo, K.; McGuire, E.; Mains, C.W.; van Doorn, E.C.; Bar-Or, D. Occurrence, predictors, and prognosis of alcohol withdrawal syndrome and delirium tremens following traumatic injury. Crit. Care Med.,  2017, 45(5), 867-874.
[http://dx.doi.org/10.1097/CCM.0000000000002371] [PMID:  28266937] 
[13] 
Long, D.; Long, B.; Koyfman, A. The emergency medicine management of severe alcohol withdrawal. Am. J. Emerg. Med.,  2017, 35(7), 1005-1011.
[http://dx.doi.org/10.1016/j.ajem.2017.02.002] [PMID:  28188055] 
[14] 
Kumar, J.; Hapidin, H.; Bee, Y.T.G.; Ismail, Z. Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats. Behav. Brain Funct.,  2013, 9, 43.
[http://dx.doi.org/10.1186/1744-9081-9-43] 
[15] 
Pal, R.S.; Mishra, A. 
            A review on 
            Dhatryadi ghrita
            .
           Int. J. Res. Ayurveda Pharm.,  2017, 8(2), 190-195.
[http://dx.doi.org/10.7897/2277-4343.082111] 
[16] 
Rani, R.; Kansal, V.K. 
            Study on cow ghee 
            
              versus
            
             soybean oil on 7,12-dimethylbenz(a)-anthracene induced mammary carcinogenesis & expression of cyclooxygenase-2 & peroxisome proliferators activated receptor-γ in rats.
           Indian J. Med. Res.,  2011, 133, 497-503.
[PMID:  21623034] 
[17] 
Pal, R.S.; Mishra, A. 
            Standardization of 
            Dhatryadi ghrita
            : A herbal ghee based ayurvedic medicinal preparation.
           Open Med. J.,  2018, 5, 47-55.
[http://dx.doi.org/10.2174/1874220301805010047] 
[18] 
Kulkarni, S.K.; Dandia, P.C. Influence of intraventricular administration of norepinephrine, dopamine and 5-hydroxytryptamine on motor activity of rats. Ind. J. Med. Res.,  1975, 63, 462-468.
[19] 
Pal, R.S.; Mishra, A. 
            Evaluation of acute toxicity of the methanolic extract of 
            Dhatryadi ghrita
             in wistar rats.
           Open Pharmacol. J.,  2019, 9, 1-4.
[http://dx.doi.org/10.2174/1874143601909010001] 
[20] 
Schoepfer, A.M.; Engel, A.; Fattinger, K.; Marbet, U.A.; Criblez, D.; Reichen, J.; Zimmermann, A.; Oneta, C.M. Herbal does not mean innocuous: Ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products. J. Hepatol.,  2007, 47(4), 521-526.
[http://dx.doi.org/10.1016/j.jhep.2007.06.014] [PMID:  17692989] 
[21] 
Antman, E.M.; Braunwald, E. ST-Elevation myocardial infarction: Pathology, pathophysiology, and clinical features. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Zipes DW, Libby P, Bonow RO, Braunwald E (eds.). 2005, 1207-32.
[22] 
Acevedo, M.B.; Nizhnikov, M.E.; Molina, J.C.; Pautassi, R.M. Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats. Behav. Brain Res.,  2014, 265, 203-215.
[http://dx.doi.org/10.1016/j.bbr.2014.02.032] [PMID:  24583190] 
[23] 
Uzbay, I.T.; Kayaalp, S.O. A modified liquid diet of chronic ethanol administration: Validation by ethanol withdrawal syndrome in rats. Pharmacol. Res.,  1995, 31(1), 37-42.
[http://dx.doi.org/10.1016/1043-6618(95)80045-X] [PMID:  7784304] 
[24] 
Sachdeva, A.; Choudhary, M.; Chandra, M. Alcohol withdrawal syndrome: Benzodiazepines and beyond. J. Clin. Diagn. Res.,  2015, 9(9), VE01-VE07.
[25] 
Sharma, L.; Sharma, A.; Gupta, G.L. Bisht, GS Protective effect of Ocimum sanctum Linn. leaf extract on ethanol withdrawal syndrome in wistar rats. Asian Pac. J. Trop. Med.,  2018, 11, 467-472.
[26] 
McMurray, M.S.; Williams, S.K.; Jarrett, T.M.; Cox, E.T.; Fay, E.E.; Overstreet, D.H.; Walker, C.H.; Johns, J.M. Gestational ethanol and nicotine exposure: Effects on maternal behavior, oxytocin, and offspring ethanol intake in the rat. Neurotoxicol. Teratol.,  2008, 30(6), 475-486.
[http://dx.doi.org/10.1016/j.ntt.2008.07.001] [PMID:  18664381] 
[27] 
Pellow, S.; Chopin, P.; File, S.E.; Briley, M. Validation of open: Closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Methods,  1985, 14(3), 149-167.
[http://dx.doi.org/10.1016/0165-0270(85)90031-7] [PMID:  2864480] 
[28] 
Montgomery, K.C. The relation between fear induced by novel stimulation and exploratory behavior. J. Comp. Physiol. Psychol.,  1955, 48(4), 254-260.
[http://dx.doi.org/10.1037/h0043788] [PMID:  13252152] 
[29] 
Handley, S.L.; Mithani, S. Effects of α-adrenoreceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour. Naunyn Schmiedebergs Arch. Pharmacol.,,  1984, 327(1), 1-5.
[30] 
Bhandari, M.R.; Kawabata, J. 
            Organic acid, phenolic content and antioxidant activity of wild yam (Dioscorea spp.) tubers of Nepal.
           Food Chem.,  2004, 88, 163-168.
[http://dx.doi.org/10.1016/j.foodchem.2003.12.027] 
[31] 
Jindal, M.N.; Kelkar, V.V.; Doctor, R.B. 
            The anorexient activity of Kalio-kund (Dioscorea bulbifera Linn.), methylphenidate and cocaine in rats: A preliminary study.
           Indian J. Med. Res.,  1969, 57(6), 1075-1080.
[32] 
Gomez, J.L.; Luine, V.N. Female rats exposed to stress and alcohol show impaired memory and increased depressive-like behaviors. Physiol. Behav.,  2014, 123, 47-54.
[http://dx.doi.org/10.1016/j.physbeh.2013.09.009] [PMID:  24096191] 
[33] 
Conrad, C.D.; Galea, L.A.; Kuroda, Y.; McEwen, B.S. Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav. Neurosci.,  1996, 110(6), 1321-1334.
[http://dx.doi.org/10.1037/0735-7044.110.6.1321] [PMID:  8986335] 
[34] 
Huynh, T.N.; Krigbaum, A.M.; Hanna, J.J.; Conrad, C.D. Sex differences and phase of light cycle modify chronic stress effects on anxiety and depressive-like behavior. Behav. Brain Res.,  2011, 222(1), 212-222.
[http://dx.doi.org/10.1016/j.bbr.2011.03.038] [PMID:  21440009] 
[35] 
McLaughlin, K.J.; Bimonte-Nelson, H.; Neisewander, J.L.; Conrad, C.D. Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: Evidence that the duration of hormone deprivation after ovariectomy compromises 17beta-estradiol effectiveness in altering CA1 spines. Horm. Behav.,  2008, 54(3), 386-395.
[http://dx.doi.org/10.1016/j.yhbeh.2008.04.010] [PMID:  18579142] 
[36] 
Yankelevitch-Yahav, R.; Franko, M.; Huly, A.; Doron, R. The forced swim test as a model of depressive-like behavior. J. Vis. Exp.,  2015, (97), 52587.
[http://dx.doi.org/10.3791/52587] [PMID:  25867960] 
[37] 
Porsolt, R.D.; Le Pichon, M.; Jalfre, M. Depression: A new animal model sensitive to antidepressant treatments. Nature,  1977, 266(5604), 730-732.
[http://dx.doi.org/10.1038/266730a0] [PMID:  559941] 
[38] 
Porsolt, R.D.; Bertin, A.; Jalfre, M. Behavioral despair in mice: A primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther.,  1977, 229(2), 327-336.
[39] 
Cryan, J.F.; Markou, A.; Lucki, I. Assessing antidepressant activity in rodents: Recent developments and future needs. Trends Pharmacol. Sci.,  2002, 23(5), 238-245.
[http://dx.doi.org/10.1016/S0165-6147(02)02017-5] [PMID:  12008002] 
[40] 
Anji, A.; Kumari, M. Supplementing the liquid alcohol diet with chow enhances alcohol intake in C57 BL/6 mice. Drug Alcohol Depend.,  2008, 97(1-2), 86-93.
[http://dx.doi.org/10.1016/j.drugalcdep.2008.03.022] [PMID:  18479843] 
[41] 
Gogoi, J.B.; Bhasin, M.; Behera, J.K.; Gairola, K.; Baruah, H. Morphometric features of asterion in adult human skulls. Int. J. Res. Med. Sci.,  2018, 6, 94-98.
[http://dx.doi.org/10.18203/2320-6012.ijrms20175536] 
[42] 
Juyal, R.; Bansal, R.; Kishore, S.; Negi, K.S. SocioDemographic Characteristics of substance abusers among intercollege students in a district of Uttrakhand. JK Sci.,  2008, 10(3), 116-119.
[43] 
Nyblom, H.; Berggren, U.; Balldin, J.; Olsson, R. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol.,  2004, 39(4), 336-339.
[http://dx.doi.org/10.1093/alcalc/agh074] [PMID:  15208167] 
[44] 
Osna, N.A.; Donohue, T.M., Jr; Kharbanda, K.K. Alcoholic liver disease: Pathogenesis and current management. Alcohol Res.,  2017, 38(2), 147-161.
[45] 
Suk, K.T.; Kim, M.Y.; Baik, S.K. Alcoholic liver disease: Treatment. World J. Gastroenterol.,  2014, 20(36), 12934-12944.
[http://dx.doi.org/10.3748/wjg.v20.i36.12934] [PMID:  25278689] 
[46] 
O’Shea, R.S.; Dasarathy, S.; McCullough, A.J. Alcoholic liver disease. Hepatology,  2010, 51(1), 307-328.
[http://dx.doi.org/10.1002/hep.23258] [PMID:  20034030] 
[47] 
Massey, V.L.; Arteel, G.E. Acute alcohol-induced liver injury. Front. Physiol.,  2012, 3, 193.
[http://dx.doi.org/10.3389/fphys.2012.00193] [PMID:  22701432] 
[48] 
Huang, X.J.; Choi, Y.K.; Im, H.S.; Yarimaga, O.; Yoon, E.; Kim, H.S. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors (Basel),  2006, 6(7), 756-782.
[http://dx.doi.org/10.3390/s6070756] 
[49] 
Sharma, L.; Sharma, A.; Gupta, G.L.; Bisht, G.S. 
            Protective effect of 
            
              Ocimum sanctum
            
             Linn. leaf extract on ethanol withdrawal syndrome in wistar rats.
           Asian Pac. J. Trop. Med.,  2018, 11, 467-472.
[http://dx.doi.org/10.4103/1995-7645.240082] 
[50] 
Uzbay, I.T.; Erden, B.F. Attenuation of ethanol withdrawal signs by high doses of L-arginine in rats. Alcohol Alcohol.,  2003, 38(3), 213-218.
[http://dx.doi.org/10.1093/alcalc/agg075] [PMID:  12711654] 
[51] 
Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked? Addict. Biol.,  2010, 15(2), 169-184.
[http://dx.doi.org/10.1111/j.1369-1600.2009.00194.x] [PMID:  20148778] 
[52] 
Victor, M. The alcohol withdrawal syndrome: Theory and practice. Postgrad. Med.,  1970, 47(4), 68-72.
[http://dx.doi.org/10.1080/00325481.1970.11697437] [PMID:  5446527] 
[53] 
Jang, W.S.; Choung, S.Y. 
            Antiobesity effects of the ethanol extract of 
            
              Laminaria japonica
            
             areshoung in high-fat-diet-induced obese rat.
           Evid. Based Complement. Alternat. Med.,  2013, 2013492807.
[http://dx.doi.org/10.1155/2013/492807] [PMID:  23365609] 
[54] 
Albani, S.H.; Andrawis, M.M.; Abella, R.J.; Fulghum, J.T.; Vafamand, N.; Dumas, T.C. Behavior in the elevated plus maze is differentially affected by testing conditions in rats under and over three weeks of age. Front. Behav. Neurosci.,  2015, 9, 31.
[http://dx.doi.org/10.3389/fnbeh.2015.00031] [PMID:  25741257] 
[55] 
Hirani, K.; Khisti, R.T.; Chopde, C.T. Behavioral action of ethanol in Porsolt’s forced swim test: Modulation by 3 alpha-hydroxy-5 alpha-pregnan-20-one. Neuropharmacology,  2002, 43(8), 1339-1350.
[http://dx.doi.org/10.1016/S0028-3908(02)00330-1] [PMID:  12527484] 
[56] 
Al-Jameil, N.; Khan, F.A.; Arjumand, S.; Khan, M.F.; Tabassum, H. Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients. Int. J. Clin. Exp. Pathol.,  2014, 7(7), 4345-4349.
[57] 
Lee, D.H.; Silventoinen, K.; Jacobs, D.R., Jr; Jousilahti, P.; Tuomileto, J. Gamma-Glutamyltransferase, obesity, and the risk of type 2 diabetes: Observational cohort study among 20,158 middle-aged men and women. J. Clin. Endocrinol. Metab.,  2004, 89(11), 5410-5414.
[http://dx.doi.org/10.1210/jc.2004-0505] [PMID:  15531490] 
[58] 
Manohar, P.R.; Eranezhath, S.S.; Mahapatra, A.; Manohar, S.R. Dhara. Digital helpline for Ayurveda research articles. J. Ayurveda Integr. Med.,  2012, 3(2), 97-101.
[http://dx.doi.org/10.4103/0975-9476.96530] [PMID:  22707867] 
[59] 
Furst, D.E.; Venkatraman, M.M.; McGann, M.; Manohar, P.R.; Booth-LaForce, C.; Sarin, R. Double-blind, randomized, controlled, pilot study comparing classic Ayurvedic medicine, methotrexate, and their combination in rheumatoid arthritis. J. Clin. Rheumatol.,  2011, 17, 185-192.

Rights & Permissions Print Cite

Article Metrics

6

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1573407216666200226092924	Print ISSN 1573-4072
Publisher Name Bentham Science Publisher	Online ISSN 1875-6646

Current Bioactive Compounds

Curative Effects of Dhatryadi ghrita Bioactive Extracts on Ethanol Withdrawal Syndrome in Wistar Rats

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract