Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

Abstract

AIM:To investigate the protective effects of melatonin on carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in experimental rats. METHODS:All rats were randomly divided into normal control group, model control group treated with CCl 4 for 12 wk, CCl 4 + NAC group treated with CCl 4 + NAC (100 mg/kg, i.p.) for 12 wk, CCl 4 + MEL-1 group treated with CCl 4 + melatonin (2.5 mg/kg) for 12 wk, CCl 4 + MEL-2 group treated with CCl 4 + melatonin (5.0 mg/kg) for 12 wk, and CCl 4 + MEL-3 group treated with CCl 4 + melatonin (10 mg/kg). Rats in the treatment groups were injected subcutaneously with sterile CCl 4 (3 mL/kg, body weight) in a ratio of 2:3 with olive oil twice a week. Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups. At the end of experiment, rats in each group were anesthetized and sacrificed. Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine changes in liver pathology. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and protein concentration were measured with routine laboratory methods using an autoanalyzer. Hydroxyproline (HYP) content in liver and malondialdehyde (MDA) and glutathione peroxidase (GPx) levels in liver homogenates were assayed by spectrophotometry. Serum hyaluronic acid (HA), laminin (LN), and procollagen Ⅲ N-terminal peptide (PⅢNP) were determined by radioimmunoassay. RESULTS:Pathologic grading showed that the fibrogenesis was much less severe in CCl 4 + MEL3 group than in model control group (u = 2.172, Moreover, treatment with melatonin (5, 10 mg/kg) significantly reduced the MDA content and increased the GPx activity in liver homogenates compared with model control group (MDA: 7.89 ± 1.49 noml/mg prot vs 6.29 ± 1.42 noml/mg prot and 6.25 ± 2.27 noml/mg prot, respectively, P = 0.015, P = 0.015; GPx: 49.13 ± 8.72 U/mg prot vs 57.38 ± 7.65 U/mg prot and 61.39 ± 13.15 U/mg prot, respectively, P = 0.035, P = 0.003). CONCLUSION:Melatonin can ameliorate CCl 4 -induced hepatic fibrosis in rats. The protective effect of melatonin on hepatic fibrosis may be related to its antioxidant activities.

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

“…Formation of fibrotic septa and increase in enzyme levels were impaired in animals treated with melatonin (5 and 10 mg/kg body weight), which is in line with previous reports on the effect of the pineal hormone in mice or rats with CCl 4 -induced fibrosis. [16][17][18][19][20][21][22] The critical step in the generation of liver fibrosis is the activation of HSCs resulting in a-SMA and collagen deposition. 28 The increased a-SMA expression in the livers of CCl 4 -treated mice was significantly diminished by melatonin administration, as indicated by immunohistochemical staining.…”

“…15 Using this toxinmediated model, it has been found that melatonin administration, at doses ranging from 2.5 to 20 mg/kg body weight, prevents liver histopathologic changes, reduces hepatic hydroxyproline content, inhibits oxidative stress and apoptosis, increases antioxidant enzyme levels, or reduces proinflammatory cytokine production, when administered intraperitoneally to rats or mice. [16][17][18][19][20][21][22] However, in these in vivo studies, effects of melatonin on the activation of HSCs and changes in the expression of fibrogenic factors or molecules involved in ECM degradation have not been tested. Moreover, because melatonin was always given before or in parallel to CCl 4 administration, only a preventive effect before the onset of liver toxicity was demonstrated.…”

The Propolis Effect on Chlorpyrifos Induced Thyroid Toxicity in Male Albino Rats

“…Chlorpyrifos damaging effects may be attributed to lipid peroxidation that could accelerate collagen synthesis by stimulating stellate cells which might cause thickened collagen fibres between thyroid follicles [38]. Weak thyroglobulin expression was explained by who reported that TGB is the thyrocytes synthesized glycoprotein and precursor for thyroid hormone [39].…”

Effect of safran, safranal and crocin which are active ingredients of Saffron (Crocus) on erythrocyte fragility and hematological parameters in carbon tetrachloride intoxicated rats

“…Oxidative stress is an important counterpart in this liver toxicity caused by CCL4. Various synthetic and natural compounds mainly from plants were tested against CCL4 toxicity (4).…”