Role of melatonin in the oxidative damage prevention at different times of hepatic regeneration

Abstract

The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na⁺/K⁺ ATPase activities in whole plasma membrane were determined. PH decreased the Na⁺/K⁺ ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na⁺/K⁺ ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier.

Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats

“…Attenuation of nitrite levels by melatonin can be regarded as the sum of indirect antioxidant effects via SOD activity and direct scavenger effect, and reduction of electron leakage. Beneficial effects of melatonin on adipocyte mitochondrial oxidative stress are in agreement with numerous reports in other tissues , pointing at mitochondria as the natural target for the antioxidant actions of melatonin.…”

“…Several works have provided evidence that melatonin improves mitochondrial respiration and mitigated oxidative stress in different pathological conditions affecting a broad range of tissues including brain liver , and cardiac and skeletal muscle . Experimental evidence suggests that in addition to improving mitochondrial respiration and alleviating oxidative stress, melatonin can directly inhibit mitochondrial permeability transition pore (mPTP) , which is involved in signaling apoptotic and necrotic cell death .…”

Melatonin suppresses activation of hepatic stellate cells through RORα‐mediated inhibition of 5‐lipoxygenase

“…Prior in vivo studies using laboratory animals have convincingly showed that melatonin has potent hepatoprotective properties in a wide array of acute and chronic liver disease models, including viral hepatitis, CCl 4 toxicity, and obstructive cholestatic‐, drug‐, or diet‐induced liver injury . In most cases, the therapeutic effects of melatonin have been attributed to its strong antioxidative capacity and/or the stimulation of antioxidant enzymes in the liver, in particular protecting the functional liver cells, the hepatocytes . Chronic injury to these hepatocytes leads to liver fibrosis.…”

Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats

“…Several studies have reported that melatonin enhances hepatic mitochondrial function, reduces oxidative stress, and improves the activities of complexes I and IV of the mitochondrial respiratory chain . Additionally, melatonin enhanced respiration rate and the increased acceptor control ratio value (ACR) in liver isolated mitochondria from streptozotocin‐induced type 1 diabetic rats and partially reduced liver damage .…”