Cardioprotective effects of minocycline against doxorubicin-induced cardiotoxicity

Biomed Pharmacother. 2023 Feb:158:114055. doi: 10.1016/j.biopha.2022.114055. Epub 2022 Dec 7.

Abstract

Background: Doxorubicin (Dox)-induced cardiotoxicity has limited its use. Inflammation, oxidative stress, and apoptosis have important roles in Dox-induced cardiotoxicity. Minocycline (Min) is an antibiotic with anti-inflammatory, anti-oxidant and anti-apoptotic properties. Here, the cardioprotective effects of Min against Dox-induced cardiotoxicity in adult male rats were evaluated.

Methods: Forty-two adult male rats were divided into six groups including control group (normal saline), Dox group, Min groups (Min 45 mg/kg and Min 90 mg/kg), and treatment groups (Dox + Min 45 mg/kg and Dox + Min 90 mg/kg). Dox (2.5 mg/kg) was administered three times a week for two weeks, and Min once a day for three weeks via intraperitoneal route. Cardiac tissue sections were stained with hematoxylin and eosin for histological examination. The activities of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) in serum as well as the activity of catalase and superoxide dismutase (SOD) in cardiac tissue were measured. Cardiac tissue levels of malondialdehyde (MDA), TNF-α, and IL-1β were also measured using ELISA.

Results: Compared with the Dox group, treatment with Min significantly decreased the activity of LDH and CK-MB. Min also increased the activity of catalase and SOD in the tissue samples. The results showed that the levels of MDA, TNF-α, and IL-1β in cardiac tissue samples were significantly lower in the Min groups compared with the Dox group. In addition, histopathological results showed that Min reduced the tissue damage caused by Dox.

Conclusion: Min reduced Dox-induced cardiotoxicity. The anti-oxidant and anti-inflammatory properties of Min may contribute to its protective effects.

Keywords: Anti-inflammation; Antioxidant; Cardiotoxicity; Doxorubicin; Minocycline.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antioxidants* / metabolism
  • Cardiotoxicity* / drug therapy
  • Cardiotoxicity* / etiology
  • Cardiotoxicity* / prevention & control
  • Catalase / metabolism
  • Doxorubicin / metabolism
  • Doxorubicin / toxicity
  • Male
  • Minocycline / pharmacology
  • Minocycline / therapeutic use
  • Myocardium / pathology
  • Oxidative Stress
  • Rats
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Catalase
  • Minocycline
  • Tumor Necrosis Factor-alpha
  • Doxorubicin
  • Superoxide Dismutase
  • Antibiotics, Antineoplastic