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The Cardioprotective Effects of Aminoguanidine on Lipopolysaccharide Induced Inflammation in Rats

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Abstract

Myocardial dysfunction, a major component of sepsis-induced multiorgan failure, contributes to the production of massive amounts of pro-inflammatory cytokines. Nitric oxide (NO) is known to act as a precursor of free radicals in inflammation. This research was conducted to assess the effect of aminoguanidine (AG) on lipopolysaccharide (LPS)-induced heart injury. 50 male rats were categorized into five groups (n = 10): (1) control, (2) LPS, (3) LPS-AG50, (4) LPS-AG100, and (5) LPS-AG150. LPS (1 mg/kg) was injected for 5 weeks, and AG (50, 100 and 150 mg/kg) was injected 30 min prior to LPS administration. All drugs were injected intraperitoneally. LPS-evolved cardiovascular toxicity was indicated by the augmentation in the level of nitric oxide (NO) metabolites, interleukin (IL)-6 and malondialdehyde (MDA), as well as reduced contents of total thiol groups, catalase (CAT), and superoxide dismutase (SOD) activity in serum, heart, and aortic tissues. In AG treated groups, noxious effects of LPS were not observed in the serum and harvested tissues. AG reduced MDA, NO metabolites, and IL- 6 and increased total thiol, CAT, and SOD activity in the heart, aorta and serum. As an inhibitor of inducible NO synthase (iNOS), AG further reduced LPS-induced oxidative stress and inflammation, hence considered as cardioprotective.

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Acknowledgements

The authors would like to thank the Vice Presidency for the Research Department of Mashhad University of Medical Sciences for their financial support (Grant Number 961380).

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Correspondence to Maryam Mahmoudabady.

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All experiments were conducted in accordance with the Animal Experimentation Ethics Committee of MUMS (Approval No. IR.MUMS.fm.REC.1397.35).

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Communicated by Y. James Kang.

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Beheshti, F., Hosseini, M., Hashemzehi, M. et al. The Cardioprotective Effects of Aminoguanidine on Lipopolysaccharide Induced Inflammation in Rats. Cardiovasc Toxicol 20, 474–481 (2020). https://doi.org/10.1007/s12012-020-09570-w

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