Effects of melatonin on colonic anastomosis healing following chemotherapy in rats

Abstract

Introduction: This study aimed to investigate the effects of melatonin on the healing of colon anastomosis following chemotherapy.

Methods: 32 rats were randomised into four groups: (a) control group, which underwent sigmoid colon transection and primary anastomosis; (b) melatonin group, which received melatonin daily following anastomosis; (c) 5-fluorouracil (5-FU) group, which received 5-FU for five days prior to anastomosis; and (d) 5-FU+melatonin group, which received 5-FU for five days prior to anastomosis and melatonin daily following anastomosis. The rats were sacrificed on Postoperative Day 7 and anastomotic bursting pressures were measured. The anastomotic segment was extracted for hydroxyproline, luminol and lucigenin measurement and histopathological examination. Blood samples were obtained from the vena cava for measurement of tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) plasma levels.

Results: Compared to the 5-FU group, bursting pressures of anastomosis and hydroxyproline levels were significantly higher, while luminol and lucigenin levels were significantly lower, in the control and 5-FU+melatonin groups. In addition, TNF-α and IL-1β plasma levels were significantly lower in the control and 5-FU+melatonin groups than in the 5-FU group. Histopathological examination showed a significant decrease in inflammation and necrosis formation in the melatonin group when compared to the control group. The positive effect of melatonin was also seen in the rats that received 5-FU.

Conclusion: Our study results showed that the adverse effects of chemotherapy on the mechanical, biochemical and histopathological parameters of anastomosis healing were attenuated through melatonin treatment.

Keywords: 5-fluorouracil; colonic anastomosis; healing; melatonin; oxidative stress.

Fig. 1

Photomicrograph of control group rat specimen shows severe inflammation in the lamina propria (arrow), polymorphonuclear leucocytes (arrowhead) and capillary vessels (*) (Haematoxylin & eosin, × 10).

Fig. 2

Photomicrograph of melatonin group rat specimen shows regressed inflammation in the lamina propria (arrow) and gland structure (*) (Haematoxylin & eosin, × 20).

Fig. 3

Photomicrograph of 5-fluorouracil group rat specimen shows anastomosis line (arrowheads) alongside the lamina propria, with inflammation (arrow) and necrosis (*) (Haematoxylin & eosin, × 20).

Fig. 4

Photomicrograph of 5-fluorouracil and melatonin group rat specimen shows apparent anastomosis line (arrowhead), apparent epithelial structure (arrows) and regressed inflammation (*) (Haematoxylin & eosin, × 20).