Reduction of cisplatin-induced renal and hepatic side effects in rat through antioxidative and anti-inflammatory properties of Malva sylvestris L. extract

Biomed Pharmacother. 2018 Oct:106:1767-1774. doi: 10.1016/j.biopha.2018.07.115. Epub 2018 Jul 31.

Abstract

Background: Cisplatin is widely used in the chemotherapy of solid organ cancers. However, its application is associated with serious side effects in various organs including the kidneys and liver.

Objectives: The aim of this study was to investigate the effects of mallow extract on the side effects of cisplatin in the kidneys and liver.

Methods: Hydroalcoholic extract of mallow, at doses of 200, 400, and 600 mg/kg BW, was administered to the animals for seven days intraperitoneally (ip). Animals in the Cis + Mallow group received a dose of cisplatin (8 mg/kg, ip) on the third day. Renal and hepatic functional disturbances were evaluated by measuring concentrations of creatinine, urea-nitrogen, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the plasma. In order to assess oxidative stress, malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) levels were measured in the kidney tissue. Then, degree of mRNA expressions of TNF-α and ICAM-1 were measured to examine renal inflammation. Hematoxylin and Eosin (H & E) staining of kidney and liver tissues was performed to study tissue damage and leukocyte infiltration.

Results: Cisplatin increased levels of plasma creatinine, urea-nitrogen, AST, and ALT; levels of tissue damage and leukocytes infiltration in the kidneys and liver; and MDA level and expression of pro-inflammatory factors in the kidney tissue. Meanwhile, it decreased FRAP level in the kidney tissue. Pretreatment by mallow extract resulted in significant improvement in all measured variables although 200-mg and 400-mg doses yielded better results.

Conclusion: Results showed that mallow supplement protects the kidneys and liver against side effects of cisplatin, and reduces the resultant oxidative stress and inflammation.

Keywords: Cisplatin; Inflammation; Malva sylvestris; Nephrotoxicity; Oxidative stress.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Aspartate Aminotransferases / blood
  • Blood Urea Nitrogen
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cisplatin*
  • Creatinine / blood
  • Cytoprotection
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Malva* / chemistry
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • ICAM1 protein, rat
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Malondialdehyde
  • Creatinine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Cisplatin