ATTENUATING EFFECTS OF KOLAVIRON ON EXPERIMENTAL COLITIS IN WISTAR RATS DURING CHRONIC CADIUM EXPOSURE

Abstract

Prevalence of Ulcerative Colitis (UC) has been attributed to environmental pollutants from industrialisation due to heavy metals accumulation. Cadmium has been implicated in the aetiology of diseases as well as interference with gut mucosal integrity. Use of synthetic drugs like sulfasalazine in the management of UC often produces unwanted side effects. However, kolaviron has been reported to attenuate UC without producing adverse effects. There is paucity of information on the effect of cadmium exposure on UC attenuation by kolaviron. Hence, its effect on colitis during chronic exposures to cadmium was investigated. Eighty-five male Wistar rats (110 – 120g) were randomly assigned into 5 groups as follows: Negative control (negCont) n=5, and n=20 in each of Positive control (posCont), Cadmium (Cd), Cadmium+Kolaviron (Cd+KV) and Kolaviron (KV). Kolaviron was extracted from Garcinia kola seeds using Soxhlet apparatus. After four weeks of cadmium (100ppm) and kolaviron (200mg/kg) administration, colitis was induced in all groups except negCont by intrarectal administration of 2 mL of 4% acetic acid (AA) and assessed based on symptoms of colitis such as weight loss and stool consistency using a diarrhoea score scale. Five rats were sacrificed before and at 3, 7, 14 days post-colitis induction in each of the treated groups. Colon samples were thereafter collected, homogenised and analysed for concentrations of Malondialdehyde, Nitric oxide (NO), Glutathione (GSH), Sulfhydryl and activities of Superoxide dismutase (SOD), Na+-K+ ATPase, Myeloperoxidase by spectrophotometry. Colonic tissue damage was assessed histopathologically (using hematoxylin and eosin Stain) using microscopy. Relative gene expressions of Tumour Necrosis Factor-alpha (TNF-α), Interleukin 10 (IL-10) and Occludin in colonic tissues were quantified by RT-PCR. Data were analysed using descriptive statistics and ANOVA at α0.05. The weight loss (%) in Cd group by week 3 relative to negCont was (31.05±0.04), while weight gain (%) in posCont and Cd+KV relative to Cd group were 36.19±0.73 and 36.17±0.51 respectively. Intrarectal administration of AA resulted in increased stool score in Cd (0.80±0.00) till day 14 post colitis induction compared with posCont (0.00±0.00) and Cd+KV (0.00±0.00). Macroscopic score was significantly increased in Cd (2.80±0.25cm) till day 14 compared with posCont and Cd+KV (0.60±0.33cm; 0.60±0.25cm). Malondialdehyde were significantly increased in Cd group by 24.6% and 13.3% on days 7 and 14, respectively. Histology showed healing in all groups post colitis induction unlike in Cd group. The notable increases in Myeloperoxidase and NO during AA-induced colitis and Cd exposure were significantly reduced by kolaviron. Significant decreases in SOD, Na+-K+ ATPase activities, sulfhydryl and GSH concentrations upon AA administration were ameliorated in other groups except Cd group. Relative gene expression of TNF-α was up-regulated while IL-10 and Occludin were down-regulated upon induction of colitis; kolaviron caused down-regulation of TNF-α while IL-10 and Occludin were up-regulated on days 7 and 14 of treatment in KV and Cd+KV groups. Kolaviron ameliorated delayed healing of acetic acid-induced colitis during cadmium exposures in Wistar rats.