Alpha-lipoic acid attenuates iron-overload-induced structural changes in the liver of the laboratory mouse (Mus musculus)

Abstract

Objectives: The role of alpha-lipoic acid in the amelioration of iron overload-induced hepatic damage remains largely underexplored. Therefore, this paper aimed at describing the structural effects of alpha-lipoic acid on the liver following iron overload in mice. Methods: After ethical approval, a total of 24 male mice were used. Twenty mice were randomly divided into two groups: A and B. Group A rats received 50 mg/kg of iron dextran intraperitoneally daily for 49 days, while those in Group B received a daily oral dose of 100 mg/kg alpha-lipoic acid by gavage in addition to the treatment in Group A. Four mice were used as normal controls. At the endpoint of the experiment, the livers were harvested and studied for iron deposition, parenchymal histoarchitecture and hepatocyte densities. Photomicrographs were taken using a digital photomicroscope for morphometric analysis. Results: Treatment of mice with iron led to a distortion of the histoarchitecture of the liver which was attenuated with co-administration of alpha-lipoic acid. Additionally, co-treatment of iron with alpha-lipoic acid resulted in significant lowering of hepatic iron deposition (p<0.001), reduction in leukocyte infiltration and significantly greater hepatocyte densities (p<0.001). Conclusion: Alpha-lipoic acid considerably attenuates the structural damage in the liver induced by iron overload.

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“…Histopathological examination is regarded as the gold standard in assessing tissue injury 32 . Our findings for histopathological observation were consistent with other studies showing different models of iron overload 5,10,23 . The liver sections of iron overloaded rats showed swelling, cytoplasmic vacuolation, apoptosis, enlarged nuclei, and hepatocytes' fatty degeneration, which is considered one of the most detrimental results of oxidative damage to lipids hepatic parenchyma 33 .…”

“…The liver is the major site for storing iron 23 . Therefore, it is considered the key organ to be adversely affected by iron overload toxicity 10 . Accumulating evidence showed that Angiotensin II is implicated in the progression of hepatic injury through induction of oxidative stress 15, 16 .…”

“…Therefore, the liver is considered the key organ to be adversely affected by iron overload toxicity 10 . Excess iron deposition within hepatocytes induces hepatic tissue damage through oxidative stress 11,12 .…”