Melatonin treatment prevents carbon tetrachloride-induced acute lung injury in rats by mitigating tissue antioxidant capacity and inflammatory response.

AIM: Carbon tetrachloride (CCl4) is an organic chemical that produces different tissue­damaging effects when ingested or inhaled. Present study aims to determine whether the application of exogenous melatonin, a neurohormone with numerous biological properties, can prevent disturbances in lung tissue antioxidative capacities and arginine metabolism, tissue inflammation and oxidative damage induced by exposure to CCl4 in rats. METHODS: The effects of melatonin on the changes occurring in rat lung tissue after an acute exposure to CCl4 were studied by monitoring alterations in antioxidant capacities, inflammatory parameters, parameters of arginine metabolism, and lipid and protein oxidative damage. RESULTS: The results indicated that melatonin prevents CCl4-induced lung damage by mitigating tissue antioxidant capacity and preventing nitric oxide production through a shift from nitric oxide synthase to arginase. Also, melatonin partially prevented tissue inflammation and molecules' oxidative modification seen after exposure to CCl4. CONCLUSIONS: The protective activity of melatonin can be attributed to its ability to scavenge both free radicals, as well as to its potential to increase tissue antioxidant capacity. The modulation of inflammatory response through both decrease in tissue inflammatory parameters and influence on arginine-nitric oxide metabolism might be an additional mechanism of action (Tab. 1, Fig. 2, Ref. 33).

Supplementation with L-arginine affects its metabolizing pathways in rat liver subjected to bile duct ligation.

Liver cholestasis is known to accompany several major liver disorders and is adequately mimicked in rats by ligation of the bile duct (BDL). L-arginine is a semi-essential amino acid which is involved in several important metabolic pathways that are significantly affected during cholestasis. This study was conducted in order to contribute to the understanding of the enrolment of L-arginine supplementation in cholestatic liver function. This was carried out by estimation of serum and liver tissue arginase activity, along with liver tissue citrulline, nitric oxide (NO) and polyamine concentrations. Rats subjected to BDL were treated for nine days with L-arginine (150 mg/kg) or remained without any treatment. Animals from two control groups were either subjected to medial laparotomy (sham/opened group) or were without any surgical treatment and received only L-arginine. Application of L-arginine prevented a significant increase in plasma bile acid and bilirubin concentrations, as well as enzyme biochemical markers that were increased after BDL. It is worth mentioning that L-arginine was able to cause a decrease in arginase activity and liver tissue NO concentrations that were found to be significantly altered during cholestasis. On the other hand, the changes occurring in the concentration of liver polyamines (putrescine, spermidine and spermine) and the activity of polyamine metabolizing enzymes were not notably affected by the administered L-arginine. The results of the present study revealed that exogenous L-arginine was able to ameliorate or prevent changes occurring in its metabolism in liver during cholestasis.