Affiliation:
1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, and
Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC),
The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical
Sciences, Tehran, Iran
2. Pharmaceutical Sciences Research Center, Ardabil University of Medical
Sciences, Ardabil, Iran
Abstract
Abstract
Background Aluminum phosphide (AlP) toxicity is associated with a high
risk of death due to heart, liver, and kidney failure as the target organs.
Phosphine gas released due to the ingestion is the main factor involved in the
multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium
sensitizer with a pleiotropic effect on multiple organs. This study aimed to
investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat
model.
Method Six groups included control group (almond oil only), sole LEV group
(48 µg/kg), AlP group
(LD50=10 µg/kg), and the poisoned groups treated
with LEV at doses of 12, 24, and 48 µg/kg 30 min
after AlP gavage. After 24 hours of treatment, serum and kidney samples
were taken for biochemical and histopathological analyses.
Result Biochemical analysis of the AlP group showed that the activity of
complexes I, II, and IV was significantly reduced, while the levels of lipid
peroxidation (LPO) and reactive oxygen species (ROS), lactate, and
myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live
renal cells and elevated necrosis. However, the levels of serum creatinine and
blood urea nitrogen were not affected by the poisoning. LEV co-treatment could
increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and
lactate levels. Additionally, the histopathological analysis showed the
detrimental effects of AlP on kidney tissue, which was mitigated by LEV
administration.
Conclusion Our findings showed that LEV can potentially improve oxidative
stress, imbalance in the redox status, necrosis, and pathological injuries in
kidney tissue following AlP-poisoning.
Subject
Drug Discovery,General Medicine
Cited by
3 articles.
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