Effect of glycine and vitamins on COX-2,TNF- and TGF-1 in CCl4 induced liver fibrosis

Abstract EN

Background Progressive fibrosis ultimately leads to gross disruption of normal liver architecture and subsequent impairment of liver function.

It has been proved that even advanced fibrosis is reversible.

So, application of cellular and molecular techniques to models of reversible fibrosis might help to establish effective antifibrotic agents which enhance the liver’s capacity for reversal of fibrosis with resolution to a normal architecture.

Aim : Current study was constructed to investigate the attenuating effect of dietary supplementation with glycine and combined vitamins (E and C) on CCl4 induced liver fibrosis in rats.

Methods: Animals were divided into 4 groups ; Group I (control group): Group II (CCl4 treated group): rats were administered CCl4 at a dose of 200 ?L / 100 gm body weight twice weekly for 9 weeks.

Group III (glycine treated group): Beside CCl4 treatment, rats received a daily oral dose of glycine (0.6 mg / kg) for 9 weeks.

Group IV (vitamins treated group): rats received CCl4 treatment as group II, simultaneously with a daily oral dose of vitamin E (50 IU/rat) and vitamin C (12.5 mg / rat) for 9 weeks.

COX-2 activity in liver tissue homogenates in addition to serum levels of TNF-? and TGF-?1 were assessed by commercial colorimetric assay and ELISA kits, respectively, to estimate their possible role in CCl4 induced liver fibrosis and if they are influenced by the applied dietary supplementations.

Results: The results indicated that CCl4 induced relevant hepatic fibrosis which was significantly attenuated by both glycine and vitamins as confirmed by serological markers of liver functions (ALT, AST, GGT, ALP and?? glucuronidase) as well as histopathological examination of liver sections.

However, the antifibrogenic effect of combined vitamins was more pronounced.

On the other hand the activity of COX-2 and serum levels of TNF-??and TGF-?1 were significantly increased upon CCl4 treatment, when compared with normal control group : [(432.62±13.48 vs 274.5 ± 5.1U / ml), 26.75 ± 0.64 vs 15.67 ± 0.56 pg / ml)and (4.61 ± 0.21 vs 0.78±0.004 ng / ml), respectively].

COX-2 activity and serum levels of TNF-? and TGF-?1 were also significantly reduced by glycine (203.87±6.39 U/ml, 17.16±0.67 pg / ml and 3.42±0.19 ng / ml, respectively) and combined vitamin supplementation (237.0±3.16 U / ml, 18.48 ± 0.56 pg / ml and 2.8 ± 0.18 ng / ml, respectively), when compared with Group II treated with CCl4 alone.

While COX-2 activity was more influenced by glycine, TGF-?? was more affected by combined vitamins and TNF-? was equally affected.

Conclusion: glycine and combined administration of vitamin E and vitamin C are suggested to have relevant ameliorating effects on CCl4 induced liver fibrosis.

However, the vitamins induced a more pronounced anti-fibrogenic effect which is mostly attributed to the synergistic action of the two vitamins .

In addition, COX-2, TNF-? and TGF-??might be involved in the pathogensis of CCl4 induced liver fibrosis and they could