title: Combination of carvacrol with methotrexate suppresses Complete Freund's Adjuvant induced synovial inflammation with reduced hepatotoxicity in rats.
abstract: The present study evaluated the therapeutic benefit of the combination of carvacrol, an isoprenoid having potential anti-inflammatory action, with methotrexate in suppressing Complete Freund's Adjuvant induced arthritis and attenuating methotrexate induced hepatic damage. Arthritis was induced in rats with Complete Freund's Adjuvant. Animals received methotrexate (2mg/kg) intraperitonealy once a week for 5 weeks alone and along with carvacrol orally (50 and 100mg/kg) respectively from the 10th to the 42nd day. Control and carvacrol alone group were also studied. Paw volume, hypernociception, and erythrocyte sedimentation rate were evaluated as arthritic markers. Hepatic marker enzymes in serum; myeloperoxidase, protein oxidation, and oxidative measures were determined in the liver homogenate. Liver histological assessments were also carried out. Methotrexate significantly controlled arthritis; however, liver damage was evident due to oxidative stress and rise in myeloperoxidase levels. Carvacrol suppressed the hyperalgesic response, significantly alleviated arthritis and reduced damage to the hepatocytes owing to a decline in the levels of myeloperoxidase and oxidative markers. High dose of the combination reduced the levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase by 24.74%, 30.2% and 28.14% compared with methotrexate treatment. Histological assessment also revealed that carvacrol minimizes methotrexate induced liver toxicity. In combination, carvacrol promoted the anti-arthritic action of methotrexate, reduced neutrophils infiltration and peroxidative damage to the liver. Therefore, carvacrol can serve as a useful adjuvant and promote the safe use of methotrexate in the management of arthritis.
authors: Department of Pharmacology and Toxicology, Nalanda College of Pharmacy, Cherlapally, Nalgonda 508001, A.P., India.
authors: Otilia J F
authors: OJ
authors: Banji
authors: Department of Pharmacology and Toxicology, Nalanda College of Pharmacy, Cherlapally, Nalgonda 508001, A.P., India. Electronic address: davidbanji@gmail.com.
authors: David
authors: D
authors: Banji
authors: Department of Pharmacology and Toxicology, Nalanda College of Pharmacy, Cherlapally, Nalgonda 508001, A.P., India.
authors: N
authors: N
authors: Soumya
authors: Department of Pharmacology and Toxicology, Nalanda College of Pharmacy, Cherlapally, Nalgonda 508001, A.P., India.
authors: Kiran Kumar
authors: KK
authors: Chilipi
authors: Department of Pharmacology and Toxicology, Nalanda College of Pharmacy, Cherlapally, Nalgonda 508001, A.P., India.
authors: C H
authors: CH
authors: Kalpana
authors: Department of Pharmaceutical Analysis, Nalanda College of Pharmacy, Cherlapally, Nalgonda 508001, A.P., India.
authors: C H
authors: CH
authors: Kranthi Kumar
authors: Department of Pharmacology and Toxicology, Rajah Muthiah Medical College, Annamalai University, Chitambaram, India.
authors: A R
authors: AR
authors: Annamalai
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001219:Aspartate Aminotransferases / Q000097:blood; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000081007:Cymenes; D004359:Drug Therapy, Combination; D005260:Female; D005620:Freund's Adjuvant; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008727:Methotrexate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013585:Synovitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; D000081007:Cymenes; D039821:Monoterpenes; D005620:Freund's Adjuvant; C073316:carvacrol; D002374:Catalase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D008727:Methotrexate
keywords: Carvacrol; Freund's Complete Adjuvant; Myeloperoxidase; Oxidative damage