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

Cancer Chemopreventive Effect of 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone on Diethylnitrosamine-Induced Early Stages of Hepatocarcinogenesis in Rats

2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation

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

Chemopreventive Potential of <i>Phyllanthus emblica</i> Fruit Extract against Colon and Liver Cancer Using a Dual-Organ Rat Carcinogenesis Model

Humans are frequently exposed to various carcinogens capable of inducing cancer in multiple organs. Phyllanthus emblica (P. emblica) is known for its strong antioxidant properties and potential in cancer prevention. However, its effectiveness against combined carcinogens remains relatively unexplored. This study aimed to assess the chemopreventive potential of the ethanolic extract of P. emblica fruits against preneoplastic lesions in the liver and colon using a rat model. Rats were administered with diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) to induce hepato- and colon carcinogenesis, respectively. The ethanolic extract of P. emblica fruit at 100 and 500 mg/kg bw significantly reduced the number of preneoplastic lesions in the liver by 74.7% and 55.6%, respectively, and in the colon by 39.2% and 40.8%, respectively. Similarly, the extract decreased the size of preneoplastic lesions in the liver by 75.2% (100 mg/kg bw) and 70.6% (500 mg/kg bw). Furthermore, the extract significantly reduced the cell proliferation marker in the liver by 70.3% (100 mg/kg bw) and 61.54% (500 mg/kg bw), and in the colon by 62.7% (100 mg/kg bw) and 60.5% (500 mg/kg bw). The ethanolic extract also enhanced liver antioxidant enzyme activities and demonstrated free radical scavenging in DPPH, ABTS, and FRAP assays. Additionally, the dichloromethane fraction of P. emblica showed significant cancer prevention potential by reducing intracellular ROS and NO production by 61.7% and 35.4%, respectively, in RAW 264.7 macrophages. It also exhibited antimutagenic effects with a reduction of 54.0% against aflatoxin B1 and 52.3% against 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mutagenesis in Salmonella typhimurium. Finally, this study highlights the chemopreventive activity of P. emblica fruit extract against the initiation of early-stage carcinogenic lesions in the liver and colon in rats treated with dual carcinogens