Ambroxol, a mucolytic agent, boosts HO-1, suppresses NF-κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF-κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti-inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO-1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF-κB signaling and its consequent target pro-inflammatory mediators, IL-6 and TNF-α. In contrast, IL-10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti-inflammatory, antioxidant, and antiapoptotic properties.

Astaxanthin Attenuates D-Galactosamine-Induced Pancreatic Injury by Activating Antioxidant Enzymes and Inhibiting VEGF-C Gene Expression.

<b>Background and Objective:</b> Astaxanthin (3,3'-dihydroxy-ß-ß-carotene-4,4'-dione) is a carotenoid, commonly found in marine environments has been reported to possess versatile biological properties including anti-inflammatory and antioxidant. In this study, the pancreatic protective effect of astaxanthin was investigated in D-Galactosamine-induced pancreas injury in rats. <b>Materials and Methods:</b> In this experimental study, MTT assay was used to determine cytotoxic effects of the Astaxanthin on pnc1 cells. A total of 30 adult albino rats divided into 5 groups, six rats in each. Group I was given an equal amount of distilled water, group II was received 400 mg kg¹ b.wt. D-galactosamine on 15th day, groups III-V were treated with astaxanthin (50 and 100 mg kg¹) and/or silymarin (50 mg kg¹) for 14 days + 400 mg kg¹ b.wt. D-galactosamine on the 15th day, respectively. <b>Results:</b> IC₅₀of Astaxanthin against the pnc1 cell line was 92.9 µg mL¹. The daily oral administration of astaxanthin (50 and 100 mg kg¹) as well as silymarin (50 mg kg¹) for 14 days to rats treated with D-galactosamine resulted in a significant improvement in plasma AST, ALT, ALP as well as pancreatic TNF-α, IL-1ß, IL-10, NO and VEGF-C gene expression. On the other hand, inducible oral administration of astaxanthin increased the activity of pancreatic GSH, SOD, GPx, GR, CAT and the level of TBARs in D-galactosamine-treated pancreatic of rats. Furthermore, Astaxanthin almost normalized these effects in pancreatic tissue histoarchitecture and MRI examination. <b>Conclusion:</b> The obtained results showed that Astaxanthin protected experimental animals against D-galactosamine-induced pancreatic injury through activation of antioxidant enzymes and IL-10 and inhibition of VEGF-C activation.