Brush border enzyme activity and expression of apoptotic marker genes in lycopene fed rats with 5-Fu induced gastrointestinal mucositis

Abstract

Background: Gastrointestinal mucositis is a common side effect of cancer chemotherapy. It is characterized by mucosal damage and barrier function alterations. Objective: We investigated the effect of single intraperitoneal dose (IP) of 5-Flurouracil (5-Fu) on the activity of brush border membrane enzymes like alkaline phosphatase (ALP), sucrase, lactase, leucine aminopeptidase (LAP) and-glutamyl transpeptidase (-GTP) in the small intestine of Wistar rats. Damage to various intestinal histopathological parameters was also examined after 5-Fu administration. Expression of various apoptotic and inflammatory marker genes in response to 5-Fu treatment was also studied. We also analysed the potential effect of lycopene supplementation in ameliorating the damage caused by 5-Fu administration. Methods: Adult male Wistar rats were randomised into four groups of ten animals each. Animals in the first group served as control, second group (5-Fu alone) was given a single IP dose of 5-Fu, third group (5-Fu + Lycopene) were orally administered lycopene, fourth group (Lycopene alone) were injected with PBS and orally given lycopene. Intestinal brush border enzyme activity was measured, followed by histopathological analyses and western blotting for protein expression studies of various apoptotic marker genes. Effect of lycopene supplementation on expression of Cox-2 was also analysed. Results: IP dose of 5-Fu resulted in a significant decrease in the activity of brush border enzymes (P < 0.05). Villus shortening and fusion, epithelial atrophy, crypt loss and inflammatory infiltrate in the lamina propria were also observed after 5-Fu treatment compared with control group (P < 0.05). There was a significant increase in protein expression of pro-apoptotic genes (Bax, Bak) after administration of 5-Fu (P < 0.05). There was an increased expression of Cox-2 in rats treated with 5-Fu alone compared to control group rats (P < 0.05). Supplementation of lycopene two days before and after a single IP dose of 5-Fu significantly improved the activity of ALP, LAP and -GTP as compared to 5-Fu group (P < 0.05). However, no such improvement was observed in case of lactase and sucrase. Inflammatory infiltrate in the lamina propria was also significantly decreased in 5-Fu + lycopene treated rats compared to 5-Fu alone treated group. There was a significant decrease in the expression of Cox-2 after lycopene supplementation (P < 0.05). Conclusion: Lycopene supplementation improved some gastrointestinal parameters after a single IP dose of 5-Fu. This may be due to the anti-inflammatory effect of lycopene. Further studies are needed to explore the potential of lycopene as a nutritional supplement for 5-Fu induced gastrointestinal mucositis.