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Modulatory and regenerative potential of transplanted bone marrow-derived mesenchymal stem cells on rifampicin-induced kidney toxicity

Danjuma L 1 , Mok PL 2 , Higuchi A 3 , Hamat RA 1 , Teh SW 2 , Koh AE 2 Show all authors , Munusamy MA 4 , Arulselvan P 5 , Rajan M 6 , Nambi A 7 , Swamy KB 7 , Vijayaraman K 8 , Murugan K 9 , Natarajaseenivasan K 10 , Subbiah SK 1

Affiliations 

  • 1 Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
  • 2 Department of Biomedical Science, Faculty of Medicine and Health Science Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
  • 3 Department of Chemical and Materials Engineering, National Central University, Jhong-li, Taoyuan, 32001, Taiwan
  • 4 Department of Botany and Microbiology, King Saud University, Riyadh, 11451, Saudi Arabia
  • 5 Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
  • 6 Biomaterials in Medicinal Chemistry Laboratory, Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, 625 021, Tamil Nadu, India
  • 7 Faculty of Medicine, Lincoln University College, Malaysia
  • 8 Department of Medical Biotechnology, Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, International Medical University, Malaysia
  • 9 Division of Entomology, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India
  • 10 Medical Microbiology Laboratory, Department of Microbiology, Centre of Excellence in Life Sciences, Bharathidasan University, Tiruchirappalli, India
Regen Ther, 2018 Dec;9:100-110.
PMID: 30525080 DOI: 10.1016/j.reth.2018.09.001

Abstract

INTRODUCTION: Anti-tuberculosis agent rifampicin is extensively used for its effectiveness. Possible complications of tuberculosis and prolonged rifampicin treatment include kidney damage; these conditions can lead to reduced efficiency of the affected kidney and consequently to other diseases. Bone marrow-derived mesenchymal stem cells (BMMSCs) can be used in conjunction with rifampicin to avert kidney damage; because of its regenerative and differentiating potentials into kidney cells. This research was designed to assess the modulatory and regenerative potentials of MSCs in averting kidney damage due to rifampicin-induced kidney toxicity in Wistar rats and their progenies. BMMSCs used in this research were characterized according to the guidelines of International Society for Cellular Therapy.

METHODS: The rats (male and female) were divided into three experimental groups, as follows: Group 1: control rats (4 males & 4 females); Group 2: rats treated with rifampicin only (4 males & 4 females); and Group 3: rats treated with rifampicin plus MSCs (4 males & 4 females). Therapeutic doses of rifampicin (9 mg/kg/day for 3-months) and MSCs infusions (twice/month for 3-months) were administered orally and intravenously respectively. At the end of the three months, the animals were bred together to determine if the effects would carry over to the next generation. Following breeding, the rats were sacrificed to harvest serum for biochemical analysis and the kidneys were also harvested for histological analysis and quantification of the glomeruli size, for the adult rats and their progenies.

RESULTS: The results showed some level of alterations in the biochemical indicators and histopathological damage in the rats that received rifampicin treatment alone, while the control and stem cells treated group showed apparently normal to nearly normal levels of both bio-indicators and normal histological architecture.

CONCLUSIONS: Intravenous administration of MSCs yielded sensible development, as seen from biochemical indicators, histology and the quantitative cell analysis, hence implying the modulatory and regenerative properties of MSCs.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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