Enrique Chávez

Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat

Background: Transforming growth factor‐β (TGF‐β) plays a pivotal role in liver fibrosis, because it activates hepatic stellate cells, stimulating extracellular matrix deposition. Cyclooxygenase‐2 (COX‐2) has been associated with TGF‐β because its inhibition decreases TGF‐β expression and collagen production in some cultured cell types.

Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCl4

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are drugs used primarily to treat inflammation, pain and fever. Their main mechanism of action is cyclooxygenase (COX) inhibition, and this enzyme has been linked to hepatotoxicity. The association of COX and liver injury has been, in part, due to the presence of COX‐2 isoform in damaged liver and the possible induction of this enzyme by profibrotic molecules like Transforming Growth Factor‐β (TGF‐β). The aim of this work was to evaluate the effects of two of the most used NSAIDs, acetyl salicylic acid (ASA) and ibuprofen (IBP), on experimental liver fibrosis. We formed experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl4 (0.4 g kg−1, i.p., three times per week, for 8 weeks) administration, and CCl4 plus ASA (100 mg kg−1, p.o., daily) or IBP (30 mg kg−1, p.o., daily). Both drugs showed important antifibrotic properties. They inhibited COX‐2 activity, prevented oxidative stress measured as lipid peroxidation and glutathione content, and ASA inhibited partially and IBP totally increased TGF‐β expression and collagen content. ASA and IBP prevented translocation of NFκB to the nucleus and, interestingly, ASA induced MMP‐2 and MMP‐13 whereas IBP induced MMP‐2, MMP‐9 and MMP‐13. As a whole, these effects explain the beneficial effects of ASA and IBP on experimental liver fibrosis. Copyright

Sulfasalazine prevents the increase in TGF-β, COX-2, nuclear NFκB translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.

It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor κB (NFκB) pathway, which regulates important genes during inflammation and immune answer. The aim of this work was to evaluate the effects of SF on carbon tetrachloride (CCl4)-induced liver fibrosis. We formed the following experimental groups of rats: controls, damage induced by chronic CCl4 (0.4 g/kg, intraperitoneally, three times a week for 8 weeks) administration and CCl4 + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We determined the activities of alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation, glutathione levels, collagen content, expression of transforming growth factor-β (TGF-β) and nuclear translocation of NFκB. SF was capable to inhibit the ALT and γ-GTP elevated levels induced with the CCl4 administration. SF had antioxidant properties, prevented the lipid peroxidation and the imbalance of reduced and oxidized glutathione produced by CCl4. Importantly, SF blocked the accumulation of collagen in the liver, the expression of TGF-β, the nuclear translocation of NFκB and the activity of COX-2, all induced with the administration of CCl4 in the rat. These results show that SF has strong antifibrotic properties because of its antioxidant properties and its ability to prevent nuclear translocation of NFκB and consequently the expression of TGF-β and the activity of COX-2.

Gadolinium Chloride Inhibits the Spontaneous Resolution of Fibrosis in CCL4-Induced Cirrhosis

Current evidence indicates that liver fibrosis is dynamic and can be bidirectional, involving phases of progression and regression, and that in addition to increased matrix synthesis, this pathological process involves major changes in the regulation of matrix degradation. There is also evidence that Kupffer cells participate in both fibrogenesis and fibrolysis. Therefore, the aim of the present work was to study the participation of Kupffer cells on the spontaneous resolution of hepatic fibrosis. Cirrhosis was produced by 3 months of chronic CCl4 intoxication in male Wistar rats, and then CCl4 was discontinued and two groups were formed: One group received gadolinium chloride (10 mg/kg, IP, daily) and the other received the vehicle (water) only for 2 months. Serum enzyme activities of alkaline phosphatase and alanine aminotransferase and liver lipid peroxidation increased by CCl4 treatment but returned to normal by discontinuation of CCl4. GSH, GSH/GSSG, and GSH+GSSG decreased significantly by CCl4, but withdrawal of CCl4 restored normal glutathione parameters. Fibrosis increased five-fold and glycogen decreased significantly by CCl4 treatment, while discontinuation of CCl4 reversed completely glycogen depletion and partially fibrosis. Gadolinium chloride showed effects only in the content of glycogen and collagen; the former was decreased further and the latter remained elevated despite discontinuation of the toxic agent. Persistent fibrosis induced by gadolinium chloride, a selective inhibitor of Kupffer cells, indicates that these cells play a pivotal role in fibrolysis.

Magnetically treated water on phytochemical compounds of Rosmarinus officinalis L.

Irrigation using water treated with static magnetic field (SMF) has recently been used as a strategy to stimulate the growth and development of different plant species. The aim of this study was to characterize the bioactive compounds and evaluate the anatomical structure of Rosmarinus officinalis L. irrigated with SMF-treated water. Results demonstrate that the treatment promoted plant growth, the number of trichomes and increased concentrations of secondary metabolites. Methanol-extracted leaves revealed that rosmarinic acid was detected in both experimental groups, without a difference in the level. Camphor, α-terpineol and verbenone were determined as the most abundant compounds present in these leaf extracts and were strongly increased in plants irrigated with SMF-treated water. Similar results were also observed for endo-borneol, bornyl acetate and β-amyrin concentrations.Taken together, these results indicate that irrigation with SMF-treated water can be used to improve the production of rosemary to obtain pharmaceutical products with an increased antioxidative activity.