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L-carnitine and Zinc supplementation impedes intestinal damage in methotrexate-treated adjuvant-induced arthritis rats: Reinstating enterocyte proliferation and trace elements
Affiliation:1. Department of Chemistry, Indian Institute of Technology Roorkee, Uttarakhand, India;2. Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, India;1. School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China;2. School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China;3. Guangxi key laboratory of Environmental Exposomics and Entire Lifecycle Health, China;4. Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, China;5. Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning 530021, China;6. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, School of Public Health, Guangxi Medical University, Nanning 530021, China;7. Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China;1. Department of Preventive Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, China;2. Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China;3. Department of Epidemiology, Biostatistics and Disease Control, School of Public Health, University for Development Studies, Tamale, Ghana;1. Department of Biological Sciences, Oakland University, Rochester, MI, USA;2. ProteinSimple, A Bio-Techne Brand, San Jose, CA, USA;3. Neurochemistry Core, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA;4. Department of Cellular Biology and Pharmacology, Albert Einstein Medical College, New York, USA;1. Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang, China;2. Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Heilongjiang Provincial Key Lab of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, Heilongjiang, China;3. Department of Public Health, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;4. Institute for Endemic Disease Prevention and Treatment of Shandong Province, Jinan 250014, Shandong, China
Abstract:BackgroundMethotrexate (MTX), a folic acid analogue, is used as a first-line treatment for rheumatoid arthritis (RA) since it has more therapeutic mechanisms than any other drug. Being an undeniable drug for the treatment of arthritis, even low-dose MTX provokes intestinal toxicity as a primary adverse effect and does not revive an anti-inflammatory element. Thus, our study aims to elucidate the anti-arthritic and prophylactic activity of supplements L-carnitine (L) and zinc (Z) against MTX-mediated intestinal damage in arthritis rats.MethodsThe rats were assessed for arthritic parameters such as body weight, paw volume, x-ray scan, and serum trace elements level. To analyze the toxic effects of MTX in the rats, intestine pH, mucosal weight, digestive enzymes, myeloperoxidase, histopathological, and immunohistochemical analysis were performed.ResultsOur study demonstrated that the arthritic parameters have shown that MTX has an ameliorative effect on arthritic rats. Besides, our findings showed that low-dose MTX (2.5 mg/kg b.w.) given once a week for two weeks during arthritis treatment had toxic effects in the rat's intestine, as evidenced by changes in intestine pH and mucosal weight, decreased digestive enzymes, increased MPO, and degenerative changes in histopathological analysis. Concurrent therapy of LZ with MTX, on the other hand, restored the modifications in these parameters.ConclusionMTX in combination with LZ effectively manages arthritis than monotherapy and significantly prevents MTX-induced intestinal damage in arthritis rats. Thus, LZ could be used as an improved therapeutic and safety for MTX-instigated intestinal damage during arthritis treatments. Therefore, our combination of L-carnitine and zinc with MTX would be promising prophylactic activity for arthritis patients.
Keywords:Rheumatoid arthritis  L-carnitine  Zinc  Methotrexate  Intestinal damage  Trace elements
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