MOLECULAR, HISTOLOGICAL, AND ANTI-OXIDANT EVALUATION OF COLITIS INDUCTION IN RATS BY DIFFERENT CONCENTRATION OF DEXTRAN SODIUM SULFATE (5 KDA)

Objective:  The current study was conceived and performed to assess the pathophysiological, histological, and molecular manipulations of dextran sodium sulphate (DSS; MW: 5,000 Da) intervention in the rat and determined the changes in the antioxidant capacity of host and representative antioxidant enzymes.Methods: Wistar rats were fed with two different concentrations (3 and 5%) of DSS for seven days and caged for another seven days. Then colon and serum samples were collected, and colitis induction was assessed by histochemical examination. The level of antioxidant enzymes were determined by spectroscopy methods, and gene regulations were evaluated by qPCR.Results: The body mass of rat was gradually reduced to DSS intervention compared to naive control. The statistically significant level of reduction in the colon length has been recorded in DSS-treated rats (3% DSS-treated: 14.33±0.53 cm; 5% DSS-treated: 13.73±0.53 cm) compared to control (Control: 17.41±0.54 cm). The total histological scores of different study groups suggested that DSS causes the significant level of damages in rat colon. The antioxidant capacity of the host was significantly reduced in terms of trolox equivalence. About three-fold higher the amount of malondialdehyde was recorded in 5% DSS-treated group compared to control. The content of antioxidant enzymes were drastically reduced (1.4-2.7 fold) upon DSS exposure than naïve control. The expression of selected inflammatory markers (IL-6, TNF-α, and iNOS) was up-regulated in DSS-exposed groups.Conclusion: The current study clearly indicated that DSS altered the expression of selected inflammatory genes, antioxidant capacity, and scavenging enzymes in such a way that it facilitates the development of colitis in Wistar rat and the study provides the necessary information the experimental designing to explore the ability of any active principle against colitis using DSS (5 KDa) induced colitis rat model.Â

Sesame Extract Promotes Chemopreventive Effect of Hesperidin on Early Phase of Diethylnitrosamine-Initiated Hepatocarcinogenesis in Rats

The combination of natural products is an alternative approach to achieving chemopreventive potential. Accordingly, citrus hesperidin exhibits numerous biological activities, including anticarcinogenic activities, while the sesamin in sesame exhibits potent anticancer activities and lipid-lowering effects. We investigated the cancer chemopreventive effects of mixed sesame and orange seed extract (MSO) containing hesperidin and sesamin in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Rats were injected with DEN once a week for 3 weeks to induce hepatocarcinogenesis. Rats were fed with MSO and various compositions that included sesame extract (SE) and hesperidin. The 10-week administration of MSO more effectively inhibited the number and size of hepatic GST-P-positive foci than hesperidin in DEN-initiated rats. MSO and hesperidin decreased the number of PCNA-positive hepatocytes but increased the apoptotic cells in DEN-induced rats. Furthermore, MSO and its constituents suppressed hepatic triglyceride content concurrently along with the expression of fatty acid synthase. Although the 5-week administration of MSO or hesperidin did not alter hepatic, preneoplastic lesion formation in DEN-initiated rats, it alleviated DEN-induced hepatotoxicity. MSO and its applied compositions did not impact upon the cytochrome P450 system. In conclusion, sesame extract promoted the chemopreventive effect of hesperidin on DEN-induced early stage of hepatocarcinogenesis in rats. The inhibitory mechanisms are likely involved with the induction of cell apoptosis, suppression of cell proliferation and modulation of hepatic lipogenesis. This study may provide revelations in the development of alternative treatments against hepatocellular carcinoma

Antigenotoxic Effects and Possible Mechanism of Red Yeast (Sporidiobolus pararoseus) on Aflatoxin B1-Induced Mutagenesis

Red yeast (Sporidiobolus pararoseus), obtained from glycerol waste in the biodiesel process, has been used as a mycotoxin sorbent in some agricultural products. This study focused on the antigenotoxic effects of red yeast on aflatoxin B1 (AFB1)-induced mutagenesis, using a Salmonella mutation assay and a rat liver micronucleus test. Red yeast was sequentially extracted to obtain hexane, acetone, hot water, and residue fractions. Carbohydrates were mainly found in hot water extract (HWE), while proteins were observed in the residue fraction. The amount of lycopene in hexane extract (HE) was higher than the amount of β-carotene in HE. All red yeast extracts were not mutagenic in the Salmonella typhimurium strains TA98 and TA100 under the presence and absence of metabolic activation. Among the extracts obtained from red yeast, HE presented the strongest antimutagenicity against AFB1-induced mutagenesis in both strains, but HWE did not show any antimutagenicity. The oral administration of red yeast, HE, and HWE for 28 days was further investigated in rats. These extracts did not induce micronucleated hepatocytes. Furthermore, they modulated the activities of some detoxifying enzymes but did not alter the activities of various cytochrome P450 isozymes. Notably, they significantly decreased hepatic micronucleus formation in AFB1-initiated rats. HE altered the activity of hepatic glutathione-S-transferase but did not affect its protein expression. Taken together, the antigenotoxicity of red yeast against AFB1-induced mutagenesis might be partly due to the modulation of some detoxifying enzymes in AFB1 metabolism. β-Carotene and lycopene might be promising antigenotoxic compounds in red yeast