Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis

Abstract

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis.

Effect of histidine on autotaxin activity in experimentally induced liver fibrosis

“…In the current study in the TAA-induced liver fibrosis group, liver hydroxyproline levels were significantly increased in comparison to the control group. This finding is in agreement with the findings of Lai et al [25], Wang et al [23], and Das et al [26].…”

Colchicine Protects against Hyperoxic Lung Injury in Neonatal Rats

“…Measurement of lipid peroxidation is a practical and safe method to evaluate the factors causing cellular injury and tissue MDA content; MDA, the last product of lipid breakdown caused by oxidative stress, is considered to be a good indicator of free radical-induced lipid peroxidation. Colchicine inhibits lipid peroxidation and stabilizes membranes [9], and prophylaxis by colchicine might have prevented an increase in lung MDA levels in our study. Our results demonstrated the protective role of colchicine in BPD development through its inhibitory action on oxygen-derived free radicals.…”

“…Besides inhibiting several leukocyte functions, such as rolling, adhesion, random mobility, phagocytosis, and cytokine secretion [8], it also inhibits phospholipase activation and decreases chemotactic responses of neutrophils to leukotriene B 4 and IL-8. In addition to its anti-inflammatory effects, colchicine also inhibits lipid peroxidation and stabilizes membranes [9]. …”

Colchicine Suppresses Osteopontin Expression and Inflammatory Cell Infiltration in Chronic Cyclosporine Nephrotoxicity

“…These benefits may be related to the anti-inflammatory action, but other possible mechanisms should be considered. First, the beneficial effects of colchicine may be attributed to its antioxidant property [37], because chronic CsA nephrotoxicity is associated with the synthesis of reactive oxygen species and peroxidation [38, 39]. An antioxidant therapy such as vitamin E has been previously shown to prevent CsA-induced toxicity [38, 39, 40, 41].…”