Research Journal of Pharmacy and Technology

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Hepato-Protective Studies of Poloxamer – 188 by Paracetomol Induced Liver Toxicity in Rats


Affiliations
1 Dept. of Pharmacology, MAK College of Pharmacy, Moinabad, Hyderabad, Telanagana, 501504, India
2 Dept. of Pharmacology, Pulla Reddy Institute of Pharmacy, Sangareddy, Hyderabad, Telanagana 502313, India
     

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Poloxamer-188 (P-188) is a polymer well renowned for possessing medical properties. Present study was conducted with an aim to evaluate Hepato-protective potential of P-188 against paracetamol induced liver damage in wistar albino rats. Group-I served as Normal control which received normal saline 5ml/kg of Body weight (BW) for 7 days. Group-II served as Negative control in which animals received same dose as mentioned in Group-I. Group-III, IV and V animals received P-188(50mg/kg), P-188(100mg/kg) and silymarin (25mg/kg) respectively for 7 days. Except Group-I all other groups challenged with a very high dose of paracetamol (750 mg/kg) to induce hepatotoxicity. Biochemical estimation results showed that SGOT, SGPT and ALP levels were increased in negative control group animals which were decreased to normal levels when treated with P-188. There was highly significant (p<0.0001) decrease of these values in all three treatment groups. Moreover decrease in P-188 treated groups is dose dependent. Histopathological study supports the results of biochemical estimation. Negative control animal showed inflammation with mild cholestasis. P-188 (50mg/kg) showed mild inflammation, more number of normal hepatocytes, whereas P-188 (100 mg/kg) showed scattered lymphocytes among normal hepatocytes and kupffer cell hyperplasia, no incidence of inflammation and necrosis. Based on these results we can conclude that P-188 is a hepatoprotective polymer.

Keywords

Poloxamer-188, Paracetamol, Hepato-Protective, Silymarin, Histopathological Study.
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  • Opoku AR, Ndlovu IM, Terblanche SE, Hutchings AH. In vivo hepatoprotective effects of Rhoicissus tridentata subsp. cuneifolia, a traditional Zulu medicinal plant, against CCl4-induced acute liver injury in rats. South African Journal of Botany. 73 (3); 2007: 372-377.

  • Arhoghro EM, Ekpo KE, Anosike EO, Ibeh GO. Effect of aqueous extract of bitter leaf (Vernonia Amygdalina Del) on carbon tetrachloride (CCl4) induced liver damage in albino Wistar rats. European Journal of Scientific Research. 26 (1); 2009: 122-130.

  • Blieden M, Paramore LC, Shah D. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States, Expert Review of Clinical Pharmacology. 7 (3); 2014: 341–348.

  • Nfila G, Lee S, Binchy J. Impact of new UK paracetamol overdose guidelines on patients presenting to the emergency department. Irish Medical Journal. 107 (2); 2014: 47–48.

  • Walubo A, Barr S, Abraham A, Coetsee C. The role of cytochrome-P450 inhibitors in the prevention of hepatotoxicity after paracetamoloverdose in rats. Human and Experimental Toxicology. 23 (1); 2004: 49–54.

  • Manokaran S, Jaswanth A, Sengottuvelu S, Nandhakumar J, Duraisamy R, Karthikeyan D, Mallegaswari R. Hepatoprotective Activity of Aerva lanata Linn. Against Paracetamol Induced Hepatotoxicity in Rats. Research Journal of Pharmacy and Technology. 1(4); 2008: 398-400.

  • Umadevi M, Maheswari C, Jothi R, Sai Kishore P, Srinivasa Reddy Y, Venkata Narayanan R. Hepatoprotective Activity of Flowers of Madhuca longifolia (Koen.) Macbr. Against Paracetamol-Induced Hepatotoxicity. Research Journal of Pharmacy and Technology. 4(2); 2011: 259-262.

  • Pradeep Kumar S, Dangi JS, Kedar Pd. Meena, Beck NR, Garima M, Aswani P. Hepatoprotective Activity of Butea monosperma bark on Liver Damage Caused by Paracetamol in Rats. Research Journal of Pharmacy and Technology. 4(5); 2011: 771-774.

  • BASF Corporation3000 Continental Drive-North Mount Olive, New Jersey.

  • Bodratti AM, Sarkar B, Alexandridis P. Adsorption of poly(ethylene oxide)-containing amphiphilic polymers on solid-liquid interfaces: Fundamentals and applications. Advances in Colloid and Interface Science. 244; 2017: 132–163.

  • Yang L, Alexandridis P. Physicochemical aspects of drug delivery and release from polymer-based colloids. Current Opinion in Colloid and Interface Science. 5 (1-2); 2000: 132–143.

  • Tadros TF. Viscoelastic properties of sterically stabilised emulsions and their stability. Advances in Colloid and Interface Science. 222; 2015: 692–708.

  • Tadros TF. Interfacial Phenomena and Colloid Stability—Industrial Applications. De Gruyter: Berlin, Germany, 2015; Volume 2.

  • Chang Y, Chu WL, Chen WY, Zheng J, Liu L, Ruaan RC, Higuchi AA. Systematic SPR study of human plasma protein adsorption behavior on the controlled surface packing of self-assembled poly (ethylene oxide) triblock copolymer surfaces. Journal of Biomedical Materials Research. Part A. 93 (1); 2010: 400–408.

  • Akash MSH, Rehman K. Recent progress in biomedical applications of Pluronic (PF127): Pharmaceutical perspectives. Journal of Controlled Release. 209; 2015: 120–138.

  • Jeong B, Kim SW, Bae YH. Thermosensitive sol–gel reversible hydrogels. Advanced Drug Delivery Reviews. 54 (1); 2002: 37-51.

  • Moon HJ, Ko DY, Park MH, Joo MK, Jeong B. Temperature-responsive compounds as in situ gelling biomedical materials. Chemical Society Reviews. 41 (14); 2012: 4860–4883.

  • Yu L, Ding J. Injectable hydrogels as unique biomedical materials. Chemical Society Reviews. 37 (8); 2008: 1473–1481.

  • Gong C, Qi T, Wei X, Qu Y, Wu Q, Luo F, Qian Z. Thermosensitive Polymeric Hydrogels As Drug Delivery Systems. Current Medicinal Chemistry. 20 (1); 2013: 79–94.

  • Duttagupta AS, Chaudhary HM, Jadhav K.R, Kadam VJ. Cubosomes: Innovative Nanostructures for Drug Delivery. Current Drug Delivery. 13 (4); 2016: 482–493.

  • Chiappetta DA, Sosnik A. Poly (ethylene oxide)-poly(propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs. European Journal of Pharmaceutics and Biopharmaceutics. 66 (3); 2007: 303–317.

  • Tanbour R, Martins AM, Pitt WG, Husseini GA. Drug Delivery Systems Based on Polymeric Micelles and Ultrasound: A Review. Current Pharmaceutical Design. 22 (19): 2016: 2796–2807.

  • Xu H, Yang P, Ma H, Yin W, Wu X, Wang H, Xu D, Zhang X. Amphiphilic block copolymers-based mixed micelles for noninvasive drug delivery. Drug Delivery. 23 (8); 2016: 3063–3071.

  • Almeida H, Amaral MH, Lobao P, Sousa Lobo JM. Applications of poloxamers in ophthalmic pharmaceutical formulations: An overview. Expert Opinion on Drug Delivery. 10 (9); 2013: 1223–1237.

  • Bromberg L. Polymeric micelles in oral chemotherapy. Journal of Controlled Release. 128 (2); 2008: 99–112.

  • Alakhova DY, Kabanov AV. Pluronics and MDR Reversal: An Update. Molecular Pharmaceutics. 11 (8); 2014: 2566–2578.

  • Srikanth MV, Murali Mohan Babu GV, Sunil SA, Sreenivasa Rao N, Praveen Kumar K, Ramana Murthy KV. Studies on the Effect of Hydrophilic Carriers in the Dissolution Rate Enhancement of Poorly Soluble Drug, Bicalutamide. Research Journal of Pharmacy and Technology. 3(2); 2010: 592-595.

  • Vaibhav A. Jagtap, Ajay N. Talele, Atul R.Bendale, Sachin Narkhede, Anil Jadhav, G. Vidyasagar. Solubility Enhancement of Pioglitazone by Using Poloxamer (188 and 407) with the Help of Kneading Method. Research Journal of Pharmacy and Technology. 3(4); 2010: 1152-1157.

  • Viraj VK, Praveen DC. Characterization of Etoricoxib Solid Dispersions Prepared By Spray Drying Technique. Research Journal of Pharmacy and Technology. 3(4); 2010: 1158-1166.

  • Chitlange SS, Pawbake GR, Pandkar SV, Wankhede SB. Formulation and Evaluation of Diacerein Solid Dispersion for Solubility and Dissolution Rate Enhancement. Research Journal of Pharmacy and Technology. 4(6); 2011: 932-937.

  • Saindane DS, Kulkarni AS, Sagri AN, Pimprikar RB, Yeshwante SB, Suryawanshi CP, Firke SD, Kale MK. Physicochemical Characterization of Solid Dispersion of Cefexime with Poloxamer 188. Research Journal of Pharmaceutical Dosage Forms and Technology. 1(2); 2009: 162-166.

  • AdamsGraves P, Kedar A, Koshy M, Steinberg M, Veith R, Ward D. RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study. Blood. 90 (5); 1997: 2041–2046.

  • Dumortier G, Kateb El, Sahli N, Kedjar M, Boulliat S, Chaumeil A. JC Development of a thermogelling ophthalmic formulation of cysteine. Drug development and industrial pharmacy. 32 (1); 2006: 63-72.

  • Vazir Ashfaq A, Shiv Kumar HG, Paranjothy KLK, Khaleel MD. Ophthalmic Drug Delivery of Diclofenac Potassium from Different Polymer Formulations: In Situ Sol Gels. Research Journal of Pharmaceutical Dosage Forms and Technology. 1(2); 2009: 158-161.

  • Kim CK, Lee SW, Choi HG. Trials of in situ gelling and mucoadhesive acetaminophen liquid suppository in human subjects, International Journal of Pharmacy. 174; 1998: 201–207.

  • Daniel JC, David AW, Raphael CL. Un Jung K, David MF. Surfactant poloxamer 188-related decreases in inflammation and tissue damage after experimental brain injury in rats. Journal of Neurosurgery: Pediatrics. 101 (2); 2004: 91-96.

  • Hartikka J, Sukhu L, Buchner C. Electroporation-facilitated delivery of plasmid DNA in skeletal muscle: plasmid dependence of muscle damage and effect of poloxamer 188. Molecular therapy. 4 (5); 2001: 407-15.

  • Boodhwani M, Feng J, Mieno S. Effects of purified poloxamer 407 gel on vascular occlusion and the coronary endothelium. European Journal of Cardio-Thoracic Surgery. 29 (5); 2006: 736-741.

  • Lee RC, River LP, Pan FS, Ji L, Wollmann RL. Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proceedings of the National Academy of Sciences of United States of America. 89 (10); 1992: 4524–4528.

  • Maria P, Yang DL, Deborah L, Rasmussen RD. Hubmayr. Poloxamer 188 Facilitates the Repair of Alveolus Resident Cells in Ventilator-injured Lungs. American Journal of Respiratory and Critical Care Medicine. 184 (8); 2011: 939- 947.

  • Veereshwarayya V, Thiruvengadam D. Hepatoprotective effect of allicin on tissue defense system in galactosamine/endotoxin challenged rats. Journal of Ethnopharmacology. 90 (1); 2004: 151-154.

  • Retimen S, Frankel SA. Colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvate transaminases. American Journal of Clinical Pathology. 28 (1); 1957: 56-63.

  • King EJ, Armstrong AR. A convenient method for determining of Serum and bile phosphatase activity. Canadian Medical Association Journal. 31 (4); 1934: 376-381.

  • Galigher AE, Kozloff EN. Essentials of practical microtechniques, 2nd ed., Lea and Febiger, Philadelphia, 1971.

  • Savides MC, Oehme FW. Acetaminophen and its toxicity. Journal of Appllied Toxicology. 3 (2); 1983: 96-111.

  • Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous Nacetylcysteine: The treatment of choice for paracetamol poisoning, British Medical Journal. 2 (6198); 1979: 1097–1100.

  • Davidson DG, Eastham WN. Acute liver necrosis following overdose of paracetamol. British Medical Journal. 2 (5512); 1966: 497-499.

  • Achliya GS, Kotgale SG, Wadodkar AK, Dorle AK. Hepatoprotective activity of Panchgavya Gritha in carbon tetrachloride induced hepatotoxicity in rats. Indian Journal of Pharmacology. 35; 2003: 308-311.

  • Moss DW, Butterworth PJ. Enzymology and medicine, Pitman Medical, London; 1974. p. 39.

  • Venkatalakshmi P, Ragadevi M. Protective effect of Tinospora cordifolia linn. on Paracetamol and Alcohol Induced Hepatotoxicity in Albino Rats. Research Journal of Pharmacy and Technology. 5(2); 2012: 281-284.


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  • Hepato-Protective Studies of Poloxamer – 188 by Paracetomol Induced Liver Toxicity in Rats

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Authors

T. Arif Hussain
Dept. of Pharmacology, MAK College of Pharmacy, Moinabad, Hyderabad, Telanagana, 501504, India
M. D. Imad Uddin
Dept. of Pharmacology, Pulla Reddy Institute of Pharmacy, Sangareddy, Hyderabad, Telanagana 502313, India
M. D. Irfan Uddin
Dept. of Pharmacology, MAK College of Pharmacy, Moinabad, Hyderabad, Telanagana, 501504, India
M. D. Nadeem
Dept. of Pharmacology, MAK College of Pharmacy, Moinabad, Hyderabad, Telanagana, 501504, India
H. Talha
Dept. of Pharmacology, MAK College of Pharmacy, Moinabad, Hyderabad, Telanagana, 501504, India
K. Prashanth
Dept. of Pharmacology, MAK College of Pharmacy, Moinabad, Hyderabad, Telanagana, 501504, India

Abstract


Poloxamer-188 (P-188) is a polymer well renowned for possessing medical properties. Present study was conducted with an aim to evaluate Hepato-protective potential of P-188 against paracetamol induced liver damage in wistar albino rats. Group-I served as Normal control which received normal saline 5ml/kg of Body weight (BW) for 7 days. Group-II served as Negative control in which animals received same dose as mentioned in Group-I. Group-III, IV and V animals received P-188(50mg/kg), P-188(100mg/kg) and silymarin (25mg/kg) respectively for 7 days. Except Group-I all other groups challenged with a very high dose of paracetamol (750 mg/kg) to induce hepatotoxicity. Biochemical estimation results showed that SGOT, SGPT and ALP levels were increased in negative control group animals which were decreased to normal levels when treated with P-188. There was highly significant (p<0.0001) decrease of these values in all three treatment groups. Moreover decrease in P-188 treated groups is dose dependent. Histopathological study supports the results of biochemical estimation. Negative control animal showed inflammation with mild cholestasis. P-188 (50mg/kg) showed mild inflammation, more number of normal hepatocytes, whereas P-188 (100 mg/kg) showed scattered lymphocytes among normal hepatocytes and kupffer cell hyperplasia, no incidence of inflammation and necrosis. Based on these results we can conclude that P-188 is a hepatoprotective polymer.

Keywords


Poloxamer-188, Paracetamol, Hepato-Protective, Silymarin, Histopathological Study.

References