Comparison between the role of n-acetylcysteine alone and with silymarin in paracetamol induced acute hepatotoxicity [clinical and experimental study]

ABSTRACT

Paracetamol [APAP], a widely used analgesic and antipyretic, is known to cause hepatic injury in high doses. N-acetylcysteine [NAC] and silymarin have been used in treatment of liver diseases of varying origins. This work was conducted to compare between the role of NAC alone and with silymarin in paracetamol induced acute hepatotoxicity. This work included both clinical and experimental studies. The clinical study included 27 patients with acute paracetamol poisoning admitted to Poisoning Treatment Unit - Zagazig University Hospitals between January and July, 2011. Sixteen patients [group I] were treated with NAC alone. Another eleven patients [group II] were treated with both NAC and silymarin. Plasma paracetamol level was measured on admission and liver function tests were assessed on admission and daily for three days. The experimental study included forty two adult male albino rats were divided into 7 groups. Group [1] negative control rats, group [2] positive control rats received distilled water, group [3] received 140mg/kg NAC, group [4] received 40mg/kg silymarin, group [5] received l000mg/kg APAP, group [6] received APAP followed by NAC in the same previous doses/ Group [7] received combined NAC and silymarin following APAP administration in the same previous doses. All drugs were given once by oral gavage. 24 hours after commencing the experiment liver function tests and hepatic glutathione [GSH] content were assessed. Liver specimens were submitted to histopathological examination and immunolocalization of BCL-2 and BrdU. It was found that combined treatment with NAC and silymarin induced a significant reduction of the elevated hepatic transaminases compared to treatment with NAC alone in both patients and rats especially patients presented late after 15 hours of APAP ingestion. Histopathological examination of hepatic specimens from combined treated rats revealed reappearance of the regular morphology of the hepatic lobules with strong immunoreactivity to BCL-2 and BrdU. Rats treated with NAC alone showed partial improvement where there were some areas of hepatocytes vacuolization, cellular infiltration, and sinusoidal dilatation, with moderate reaction for both BCL-2 and BrdU. This was accompanied with a significant elevation of the mean values of hepatic GSH in combined treated rats compared to those treated with NAC alone. It was concluded that both silymarin and NAC have a synergistic effect, and combined treatment with both of them could be used as a beneficial treatment for paracetamol acute hepatotoxicity especially for late presented cases