Antitumor activity of sitagliptin and vitamin B12 on Ehrlich ascites carcinoma solid tumor in mice.

This study was carried out to investigate the potential effects of vitamin B12 and sitagliptin, and their possible synergistic effect with doxorubicin (DOX) on the Ehrlich solid tumor model. B12, sitagliptin, and their combination with DOX were administered to tumor-bearing mice for 21 days. Treatment with B12, sitagliptin, as well as their combinations with DOX caused a significant inhibition of tumor growth and increased the survival time. Malondialdehyde levels and the relative expression of tumor necrosis factor-α and nuclear factor kappa B were significantly decreased, whereas the total antioxidant capacity was significantly increased in all treated groups, except the DOX-treated one, when compared with the positive control group. Moreover, increased apoptosis was also observed by increased cleaved caspase-3 immunostaining and histopathological examination. In conclusion, the antitumor activity of B12 and sitagliptin could be attributed to their ability to induce apoptosis and suppress oxidative stress and inflammation.

The effect of fucoidan or potassium permanganate on growth performance, intestinal pathology, and antioxidant status in Nile tilapia (Oreochromis niloticus).

Fucoidans are marine algal sulfated glycans that are widely used as dietary additives in aquaculture. These glycans are recognized as beneficial supplements for their antimicrobial, anti-inflammatory, anticancer, and antiviral properties. Potassium permanganate is another commonly used chemical that is used in aquaculture to treat infections in fish. Despite their widespread use, there are few data available regarding the potential sublethal toxicity associated with fucoidan and potassium permanganate treatments of fish. In this study, we investigated the effect of each compound on the growth, intestinal health, and antioxidant status of Nile tilapia (Oreochromis niloticus). Both compounds affected the growth of experimental fish compared with untreated fish. However, while growth parameters were positively associated with the dose of fucoidan administered, growth was negatively associated with the dose of potassium permanganate in Nile tilapia. Fucoidan treatment was observed to improve the intestinal health of fish based upon increases in intestinal villous area, intestinal villous length and width, and the intraepithelial lymphocyte number and decreases in the total intestinal bacterial count compared with untreated fish. Conversely, potassium permanganate induced intestinal epithelium proliferation and villous branching, a histopathological response typically observed with chemical irritants. Both fucoidan and potassium permanganate decreased levels of oxidative and nitrosative stress markers and enhanced the antioxidant status in multiple organs. Taken together, fucoidan dietary application improved the growth, intestinal health, and antioxidant status in Nile tilapia, supporting the use of this compound as a promising feed additive for aquaculture production. Conversely, potassium permanganate baths have negative effects on fish growth at higher doses and appeared to act as a gastrointestinal irritant in tilapia. This study improves knowledge regarding the biochemical and histological responses in Nile tilapia to two widely used aquaculture-related treatments.

Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease characterized by fat deposits in liver cells, which can lead to hepatitis and fibrosis. This study attempted to explore the protective effect of vitamin D3 (VitD) against NAFLD. Methods: Adult male albino rats were randomized into four separate groups: the negative control group was fed a standard rat chow; the positive group received a high-fat diet (20%) and 25% fructose water (NAFLD); the VitD control group was intramuscularly treated with VitD (1,000 IU/kg BW) 3 days per week for 10 weeks; and the NAFLD group was treated with VitD therapy. Biochemical and hepatic histological analyses were performed. Hepatic oxidative stress and inflammatory conditions were also studied. Hepatic expression of sterol regulatory element-binding protein 1-c (SREBP-1-c), peroxisome proliferator-activated receptor alpha (PPAR-α), and insulin receptor substrate-2 was analyzed by quantitative real-time polymerase chain reaction. Results and discussion: The NAFLD rats exhibited elevated terminal body weight, hepatic injury markers, dyslipidemia, glucose intolerance, and insulin resistance. Moreover, the NAFLD rats had increased SREBP-1-c expression and reduced PPAR-α and IRS-2 expressions. Histological analysis showed hepatic steatosis and inflammation in the NAFLD group. In contrast, VitD administration improved the serum biochemical parameters and hepatic redox status in NAFLD rats. Also, VitD treatment ameliorated hepatic inflammation and steatosis in the NAFLD group by decreasing the expression of SREBP-1-c and increasing the expression of PPAR-α. Overall, these results suggest that VitD could have a protective effect against NAFLD and its associated complication.

Effects of Resveratrol Against Induced Metabolic Syndrome in Rats: Role of Oxidative Stress, Inflammation, and Insulin Resistance.

Metabolic syndrome (MS) is a serious health problem associated with an increase in risk factors for hepatic steatosis, which is the most common liver disease today. The goal of this study was to investigate the protective effects of resveratrol against metabolic alterations associated with a high-fat high-fructose diet (HFFD). Thirty-two male rats were randomly divided into four equal groups: control (cont.), metabolic syndrome (MS), resveratrol (Res), and metabolic syndrome treated with resveratrol (MS + Res). Resveratrol was administrated orally at a dose of 30 mg/kg·bw, daily. After 10 weeks, body weight, serum biochemical parameters, hepatic oxidative stress, inflammatory markers, as well as mRNA levels of hepatic genes related to lipid metabolism and insulin signaling were measured. In addition, the liver was examined histopathologically to detect lipid deposition. Increased body weight, hepatic dysfunction, dyslipidemia, hepatic insulin resistance, hepatic oxidative and inflammatory stress conditions, upregulation of mRNA expression level of sterol regulatory element binding protein 1-c (SREBP1-c), and downregulation of mRNA expression levels of peroxisome proliferated activated receptor alpha (PPARα) and insulin receptor substrate-2 (IR-S2) were all observed in the MS rats. Hepatic steatosis was confirmed by hematoxylin and eosin and Oil Red O staining. Administration of resveratrol reduced liver steatosis, oxidative stress, and inflammatory state. Also, it improved lipid profile as well as insulin sensitivity and reverted alterations in hepatic mRNA expression levels of the tested genes. Based on these findings, resveratrol could be proposed as a therapeutic approach for MS prevention.

Fucoidan ameliorates acute and sub-chronic in vivo toxicity of the fungicide cholorothalonil in Oreochromis niloticus (Nile tilapia).

Fucoidans are sulfated glycans from marine algae that have both anti-cancer and anti-microbial properties. Chlorothalonil is a fungicide and insecticide commonly used in agriculture. Chlorothalonil is relatively toxic to fish and can potentially affect the aquaculture practices. In this study, we determined whether fucoidan administration would offer any protection from acute and subchronic toxicity of chlorothalonil on Nile tilapia. First, we tested the effect of chlorothalonil (20 to 140 µg/L, water-applied) on Nile tilapia in an acute exposure (six days). Survival analysis was performed, together with assessment of histopathology, oxidative stress (i.e., antioxidant status, hydrogen peroxide levels, malondialdehyde and nitric oxide levels) and immunohistochemistry to measure indicators of hepatic damage (i.e., caspase 3, p53, mini-chromosome maintenance proteins (MCM), and glutathione peroxidase). Chlorothalonil induced mild to severe histopathological alterations that were dose-dependent in various tissues of Nile tilapia. Chlorothalonil also induced oxidative stress as indicated by elevated biochemical markers. The highest recorded mortalities were associated with p53 expression. Additional feeding experiments were conducted with fucoidan (8 g/kg diet), following acute (40 µg/L for seven days) and sub-chronic (20 µg/L for six weeks) chlorothalonil application in Nile tilapia. Many of these same biochemical biomarkers of stress, oxidative damage response, and tissue pathology (evidence for hepatic neoplasm) were ameliorated by fucoidan, suggesting a protective effect of the compound. Agrochemicals are ubiquitous on a global scale, and the use of fucoidan as a feed additive may be beneficial for protecting aquatic animal health and aquaculture species from the impacts of chemical run-off.

Ameliorative effect of curcumin against lead acetate-induced hemato-biochemical alterations, hepatotoxicity, and testicular oxidative damage in rats.

Lead, toxic heavy metal of global concern, induces toxicity in various organs via oxidative stress. Thereby, in this study, the protective role of curcumin against lead acetate-induced toxicity was evaluated. Thirty-two male albino rats were allocated equally into four groups and orally administered with corn oil as a vehicle (Cont.), curcumin (CUR) (400 mg/kg bw), lead acetate (LA) (100 mg/kg bw), and lead acetate plus curcumin (LA + CUR). All rats had received their treatments daily for 4 weeks. The results revealed that LA toxicity induced normocytic normochromic anemia with significant leukocytosis and lymphocytosis. Moreover, LA-intoxicated rats showed a marked elevation in the liver enzyme activities, serum cholesterol, and triglyceride levels. In contrast, sero-immunological parameters, total protein, albumin, globulin, and testosterone levels were significantly reduced compared to the control rats. Additionally, LA-induced hepatic and testicular oxidative damage revealed by marked increased in MDA level with prominent reduction in the antioxidant system. The gene expression of the hepatic pro-inflammatory markers and testicular steroidogenic biomarkers including LHR and aromatase were significantly upregulated; meanwhile, the expressions of testicular StAR, CYP17a, 3B-HDS, SR-B1, and P450SCC were significantly downregulated in the LA-intoxicated group. Curcumin treatment could partially improve the hematological, biochemical, and histopathological alterations induced by LA. Also, it was observed that curcumin significantly restored hepatic pro-inflammatory markers and testicular steroidogenic enzymes. In conclusion, curcumin has antioxidant, anti-inflammatory, and immunomodulatory effects and is able to minimize the LA-induced oxidative damage in rats.

Comparative effects of Herba Cox®, a commercial herbal extract, on rabbits (Oryctolagus cuniculus) experimentally infected with Eimeria stiedae.

The objective of this study was to evaluate the efficacy of Herba Cox®, a commercial herbal compound containing extracts from Bombax malabaricum, Aegle marmelos, Anethum foeniculum, Resina salvia, Ferula asafoetida and Papaver somniferum, for the treatment of rabbit hepatic coccidiosis. Thirty rabbits were allocated into three groups (10 × 3), the G1 group served as a negative control group, G2 group (positive control group) was infected with 5 × 104 sporulated E. stiedaeoocysts and served as infected-untreated group, and G3 group was infected with 5 × 104 sporulated E. stiedaeoocysts and treated with Herba Cox®, 1 ml/liter of drinking water, starting 7 days before infection and continuing for 4 weeks post-infection. When compared to the infected group (G2), body weight and weight gain were significantly (P ≤ 0.05) increased, the feed conversion rate was improved and no mortality was detected in infected treated group (G3) and similar to negative control group (G1). In addition, faecal oocyst output and liver enzymes were significantly decreased. Malondialdehyde, nitric oxide, and glutathione concentrations observed in G3 were similar to those in G1. In infected-untreated rabbits (G2), the haemoglobin, lymphocytes, and CD4+/ CD8+ ratio were significantly decreased, while the total leukocyte count, percentage of heterophils, and heterophil/lymphocyte ratio were increased. Significantly more severe histopathological hepatic lesions were observed in G2 when compared to G1 and G3. In conclusion, the obtained results showed that Herba Cox® should be considered a safe and novel effective compound for the treatment of E. stiedae infection in rabbits.