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Protective Role Of Montelukast In Methotrexate Induced Toxicity In Rats

By: Saima Malik (2014-VA-230) | Dr. Khalid Abdul Majeed.
Contributor(s): Dr Muhammad ShahbazYousaf | Dr.Hafsa Zaneb.
Material type: materialTypeLabelBookPublisher: 2016Description: 58p.Subject(s): Department of PhysiologyDDC classification: 2505-T Dissertation note: Methotrexate (MTX) is an antifolate drug which is used to treat a variety of Autoimmune Diseases e.g rheumatoid arthritis, psoriasis and different types of cancers. However, MTX toxicity limit its use which include oxidative stress in causing toxicity on the liver, kidney, heart and other organs.Montelukast is a leukotriene antagonist.Recent evidence suggests that montelukast possessesantioxidant and anti-inflammatoryactivity.Thirty (n=30) adult albino ratswere selected and housed in stainless steel cages in the Experimental Animal shed, Department of Physiology, University of Veterinary and Animal Sciences, Lahore. The rats were randomly divided into five groups having six rats in each group. Animals were treated by following treatment plan; Group 1: (Negative Control) injected I/P with physiological saline from day zero to day four and then injected with 2 % ethanol from day four to day ten. Group 2: (MK positive control) injected I/P with MK (10mg/kg body weight, BW) from day four to day ten for consective seven days. Group 3:(MTX positive control) injected at day zero I/P with a single dose of MTX (20mg/kg BW) per ten days. Group 4:(MTX-MK 5) injected at day zero I/P with a single dose of MTX (20mg/kg BW) and then injected I/P with MK (5mg/kg BW) from day four to day ten for consective seven days. Group 5: (MTX-MK 10) injected at day zero I/P with a single dose of MTX (20mg/kg BW) and then injected I/P with MK (10mg/kg BW) from day four to day ten for consective seven days. Data was analyzed by one way analysis of variance using SPSS software (SPSS Inc. version 20, Chicago, Illinois). The group differences werestudied by using Duncan’s multiple range tests. The P value <0.05 was considered as significant. Data was presented as mean ± SD. Body weight and feed intake was analyzed by using repeated measure analysis. The current study showed reduction in feed and water intake and shows diarrhea like symptoms which ultimately results in gradual reduction in body weight in MTX treated groups when compared with control group. While non MTX treated groups shows increase in feed consumption and ultimately increase in body weight. BUN and creatinine level were increased after MTX administration which was reduced after MK treatment. MK10mg/kg BW dose administered to G5 after MTX was more effective compared to 5mg/kg BW dose of MK administered to G4 after MTX treatment. Enzymatic level of MDA and catalase in serum, liver and kidney tissue were increased after MTX administration in G3, G4 and G5.There was no highly significant results found after MK treatment due to Low dose of MK which was unable to maintain the enzymatic level after induction of imbalance between oxidant and antioxidant level. Conclusion: From our study we have concluded that montelukast administration after methotrexate induced toxic effect on renal function test and hematological parameters, it can significantly normalize the level of BUN and creatinine also shows significant improvement in Hb and RBCs level. While there was no significant effect found on oxidative stress due to insufficient dose of MK.
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Methotrexate (MTX) is an antifolate drug which is used to treat a variety of Autoimmune Diseases e.g rheumatoid arthritis, psoriasis and different types of cancers. However, MTX toxicity limit its use which include oxidative stress in causing toxicity on the liver, kidney, heart and other organs.Montelukast is a leukotriene antagonist.Recent evidence suggests that montelukast possessesantioxidant and anti-inflammatoryactivity.Thirty (n=30) adult albino ratswere selected and housed in stainless steel cages in the Experimental Animal shed, Department of Physiology, University of Veterinary and Animal Sciences, Lahore. The rats were randomly divided into five groups having six rats in each group. Animals were treated by following treatment plan;
Group 1: (Negative Control) injected I/P with physiological saline from day zero to day four and then injected with 2 % ethanol from day four to day ten.
Group 2: (MK positive control) injected I/P with MK (10mg/kg body weight, BW) from day four to day ten for consective seven days.
Group 3:(MTX positive control) injected at day zero I/P with a single dose of MTX (20mg/kg BW) per ten days.
Group 4:(MTX-MK 5) injected at day zero I/P with a single dose of MTX (20mg/kg BW) and then injected I/P with MK (5mg/kg BW) from day four to day ten for consective seven days.
Group 5: (MTX-MK 10) injected at day zero I/P with a single dose of MTX (20mg/kg BW) and then injected I/P with MK (10mg/kg BW) from day four to day ten for consective seven days.
Data was analyzed by one way analysis of variance using SPSS software (SPSS Inc. version 20, Chicago, Illinois). The group differences werestudied by using Duncan’s multiple range tests. The P value <0.05 was considered as significant. Data was presented as mean ± SD. Body weight and feed intake was analyzed by using repeated measure analysis.
The current study showed reduction in feed and water intake and shows diarrhea like symptoms which ultimately results in gradual reduction in body weight in MTX treated groups when compared with control group. While non MTX treated groups shows increase in feed consumption and ultimately increase in body weight. BUN and creatinine level were increased after MTX administration which was reduced after MK treatment. MK10mg/kg BW dose administered to G5 after MTX was more effective compared to 5mg/kg BW dose of MK administered to G4 after MTX treatment. Enzymatic level of MDA and catalase in serum, liver and kidney tissue were increased after MTX administration in G3, G4 and G5.There was no highly significant results found after MK treatment due to Low dose of MK which was unable to maintain the enzymatic level after induction of imbalance between oxidant and antioxidant level.
Conclusion: From our study we have concluded that montelukast administration after methotrexate induced toxic effect on renal function test and hematological parameters, it can significantly normalize the level of BUN and creatinine also shows significant improvement in Hb and RBCs level. While there was no significant effect found on oxidative stress due to insufficient dose of MK.


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