MODULATORY EFFECTS OF DIETARY INCLUSION OF CRAB-CHITOSAN ON RENAL DYSFUNCTION ASSOCIATED WITH 1, 2-DIMETHYLHYDRAZINE-INDUCED COLORECTAL CANCER IN MALE WISTAR RATS

Abstract

ABSTRACT Renal dysfunction is a significant complication in patients with colorectal cancer (CRC) and is 12 associated with high morbidity and mortality. Studies have reported that 35% of CRC cases are 13 linked to dietary factors. This study investigated the modulatory effects of dietary inclusion of 14 chitosan on renal dysfunction associated with CRC in male Wistar rats induced with 65 mg/kg b.w.t 15 of 1,2-dimethylhydrazine (DMH). Forty-nine male Wistar rats (80–100) g were separated into seven groups (n=7): normal control, DMH control, DMH + 2.5% chitosan, DMH + 5% chitosan, 17 DMH + 7.5% chitosan, DMH + standard drug (capecitabine - 10 mg/kg b.wt.), and Diet control(7.5% chitosan). The DMH was administered subcutaneously weekly for six weeks followed by chitosan-inclusion diets given for eight weeks. The normal control, DMH control and DMH +standard drug groups were fed normal diet. Samples of blood, colon, and kidney were taken and processed using standard methods for biochemical, haematological, geneexpression and histopathological analyses. Data were analyzed using one-way analysis of variance, followed by Duncan’s multiple range test; p < 0.05 was considered significant. The DMH control group showed elevated (9.4 fold) serum carcino-embryonic antigen when compared with the normal control, which was significantly (p < 0.05) reduced by 76% following chitosan treatment. The chitosaninclusion diets significantly (p < 0.05) increased the DMH-reduced creatinine (29 and 5.8) fold, and urea (53 and 31)% in the serum and kidney, respectively. Additionally, chitosan increased the DMH-reduced levels of calcium (1.7, 12.2, and 2.6) fold and magnesium (41, 284, and 6)%, inserum, kidney and colon, respectively. However, the effect of chitosan was observed only onsodium level in serum (71%) and kidney (242%), and colon potassium (71%). Furthermore, activities of Na+/K+- and Ca2+/Mg2+-ATPases were significantly (p < 0.05) inhibited in the kidney and colon of DMH control group, but was dose-dependently reversed by chitosan diets. There were significant (p < 0.05) increases in levels of malondialdehyde (22, 30 and 33)% and reducedglutathione (23, 18 and 19)%, and 5' nucleotidase activity (0.2, 1.2 and 2) fold, respectively inserum, kidney and colon of DMH control compared with normal control. Gamma-glutamylcysteine ligase and glutathione reductase activities were significantly (p < 0.05) activated, respectively in the kidney (2.7 and 2.2) fold and colon (3 and 3.1) fold of DMH control compared to normal control. The reverse was observed for vitamin E level in all the compartments and vitamin C in kidney and colon. Furthermore, the DMH control group exhibited significantly (p < 0.05) down-regulated adenomatous polyposis coli, β-catenin, and βcl2 genes; however, dietary inclusion of chitosansignificantly abrogated this effect. Also, basophils significantly (p < 0.05) increased by 60% while eosinophils decreased by 97% in DMH control when compared to normal control; these changes were alleviated in groups given chitosan. Altered nephrotic and colonic architecture observed inDMH control were effectively remedied with chitosan. Conclusively, chitosan at 7.5% effectively ameliorated renal dysfunction associated with 1,2-dimethylhydrazine-induced colorectal carcinogenesis.