Effect of Age on Colonic Damage Induced by Cadmium Exposure in Female Wistar Rats

Abstract

Background: Cadmium, a known genotoxic metal, has been shown to worsen colonic damage in both animal models and human studies. Research has indicated that cadmium accumulation in the colon results in mucosal damage, inflammation, disrupted immune responses, and an increased risk of gastrointestinal diseases. However, the relationship between age-related changes in the colon and cadmium exposure is not well understood. This study aimed to examine how age affects colonic damage caused by cadmium exposure in female Wistar rats. Methods: Forty eight (48) female Wistar rats were allotted for this study. They were divided into six groups with eight animals each as follows: Group one: control group for young (6 weeks old) female Wistar rats, group two: cadmium exposed young (6 weeks old) female Wistar rats, group three: control group for middle age (10 weeks old) female Wistar rats, group four: cadmium exposed middle age (10 weeks old) female Wistar rats, group five: control group for old (24 weeks old) female Wistar rats group six: cadmium exposed old (24 weeks old) female Wistar rats. Cadmium exposed animals were exposed to 50mg/kg body weight of CdCl2 orally for 28 days and Animals in control groups received 0.5 ml of distilled water each ensuring uniformity and consistency of exposure across the experimental groups. The animals were weighed daily throughout the exposure period. Rats were sacrificed on the 29th day by cervical dislocation. The colon was excised and the distal portion was homogenized and assessed for antioxidants level [Superoxide Dismutase (SOD), catalase (CAT), reduced glutathione (rGSH)], oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA)] spectrophotometrically, and inflammatory marker [tumor necrosis factor (TNF-α)] using ELISA. Histological evaluation was assessed from the mid portion of the colon using Hematoxylin and Eosin staining method. Total intestinal bacterial count was done microscopically. Data were analyzed using One Way Analysis of Variance (ANOVA) Graphpad prism 5.0, Tukey’s Post-hoc test was used for multiple comparison with statistical significance set at P<0.05. Results and Discussion: The result shows a significant reduction in the body weight of Cd exposed young and middle-age groups only compared with their respective control groups (P=0.001; 0.05). There was no significant difference in SOD activity among Cd exposed groups, except a reduction in the old group compared to the middle-age group (P=0.001). Catalase activity and GSH levels decreased in both middle-age and Cd exposed old-age groups (P=0.01; 0.05) compared to their controls and Cd exposed young age group. MDA and 8-OHDG levels increased significantly in the Cd exposed old-age group (P=0.01) compared to its control. TNF-α and total colonic bacterial count were significantly increased in the Cd exposed old-age group compared to other Cd exposed groups (P=0.001; 0.001). Histological examination showed different tissue damage patterns in the colon across Cd-exposed age groups, with more severe changes in older rats. Conclusion: Exposure to cadmium induced age related intestinal damage through increase in permeability, oxidative stress and impaired defense system.