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.

In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network.

Chemoresistance to 5-fluorouracil (5-FU) is common during colorectal cancer (CRC) treatment. This study measured the chemotherapeutic effects of 5-FU, active vitamin D3 (VD3), and/or metformin single/dual/triple regimens as complementary/alternative therapies. Ninety male mice were divided into: negative and positive (PC) controls, and 5-FU, VD3, Met, 5-FU/VD3, 5-FU/Met, VD3/Met, and 5-FU/VD3/Met groups. Treatments lasted four weeks following CRC induction by azoxymethane. Similar regimens were also applied in the SW480 and SW620 CRC cell lines. The PC mice had abundant tumours, markedly elevated proliferation markers (survivin/CCND1) and PI3K/Akt/mTOR, and reduced p21/PTEN/cytochrome C/caspase-3 and apoptosis. All therapies reduced tumour numbers, with 5-FU/VD3/Met being the most efficacious regimen. All protocols decreased cell proliferation markers, inhibited PI3K/Akt/mTOR molecules, and increased proapoptotic molecules with an apoptosis index, and 5-FU/VD3/Met revealed the strongest effects. In vitro, all therapies equally induced G1 phase arrest in SW480 cells, whereas metformin-alone showed maximal SW620 cell numbers in the G0/G1 phase. 5-FU/Met co-therapy also showed the highest apoptotic SW480 cell numbers (13%), whilst 5-FU/VD3/Met disclosed the lowest viable SW620 cell percentages (81%). Moreover, 5-FU/VD3/Met revealed maximal inhibitions of cell cycle inducers (CCND1/CCND3), cell survival (BCL2), and the PI3K/Akt/mTOR molecules alongside the highest expression of cell cycle inhibitors (p21/p27), proapoptotic markers (BAX/cytochrome C/caspase-3), and PTEN in both cell lines. In conclusion, metformin monotherapy was superior to VD3, whereas the 5-FU/Met protocol showed better anticancer effects relative to the other dual therapies. However, the 5-FU/VD3/Met approach displayed the best in vivo and in vitro tumoricidal effects related to cell cycle arrest and apoptosis, justifiably by enhanced modulations of the PI3K/PTEN/Akt/mTOR pathway.

Pulsed high-intensity laser therapy versus low level laser therapy in the management of primary dysmenorrhea.

[Purpose] To determine the effect of pulsed high intensity laser therapy (HILT) versus low level laser therapy (LLLT) in the treatment of primary dysmenorrhea. [Participants and Methods] This was a randomized clinical trial that included 30 females diagnosed with primary dysmenorrhea who were assigned randomly into two groups of equal numbers. The treatment was three sessions every cycle for three consecutive cycles, where group (A) received pulsed HILT and group (B) received LLLT. All participants were evaluated before and after treatment sessions by visual analogue scale (VAS) and at the end of treatment by pain relief scale (PRS). [Results] The results showed a significant decrease in the severity of pain in the two groups. Comparison between the two groups showed a statistically non-significant difference in the severity of pain and pain alleviation at the end of the treatment course. [Conclusion] Both pulsed HILT and LLLT are effective in the treatment of primary dysmenorrhea, with no significant differences between the two modalities.

The remedial effect of Thymus vulgaris extract against lead toxicity-induced oxidative stress, hepatorenal damage, immunosuppression, and hematological disorders in rats.

The Thymus vulgaris (T. vulgaris) has been used in foods for the flavor, aroma, and preservation and in folk medicines. The objective of the present work was to determine the antioxidant and protective effects of T. vulgaris extract against lead (Pb)-intoxicated rats. A thirty-two male Sprague-Dawley were randomly assigned into 4 equal groups and treated for six weeks as follows: group I (GP-I), served as negative control; GP-II, -III, and -IV received either Pb acetate in drinking water (500 mg/L), T. vulgaris extract (500 mg/kg/day) by oral gavage or Pb acetate with T. vulgaris extract, respectively. Blood samples were collected at the end of the study week 6 to measure the hepatic and renal biochemical markers, complete blood count alongside the serum levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis (TNF)-α, and interferon (IFN)-γ. Additionally, liver and kidney tissue specimens were collected for histopathology as well as to measure the antioxidant-reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) alongside the lipid peroxidation marker, malonaldehyde (MDA). The results indicated that Pb toxicity increased the serum levels of IL-1ß, IL-6, and TNF-α, whereas IL-10 and IFN-γ were reduced. The results showed disturbed liver and renal functions; increased serum levels of ALT, AST, ALP, total bilirubin, creatinine, and urea; and decreased total protein, albumin, and calcium. The GSH, Gpx, and CAT levels were significantly decreased in the Pb-administrated group, while MDA was increased. However, regarding the hepatorenal markers, those animals treated with T. vulgaris alone did not induce any significant changes. Moreover, the combined treatment with T. vulgaris extract together with Pb showed significant improvement in Pb-induced toxicity in all the tested parameters compared to the negative control group. We investigated the potential protective effects of the medicinal plant T. vulgaris in vivo, since there are no publications that address the potential protective effect of this leaf extract against Pb-induced hepatorenal toxicity. Our studies concluded that the T. vulgaris extract reduces Pb overload in hepatorenal tissues, and that this has a potential immunomodulatory role, antioxidant activity, and a protective effect against Pb toxicity.

Significance of clinical observations and biochemical alterations in buffalo calves with dietary abomasal impaction.

BACKGROUND: The present study aimed to throw light on the clinical characteristics of abomasal impaction in buffalo calves and its associated biochemical alterations. For this reason, a total of 20 male buffalo calves (Bubalus bubalis) with abomasal impaction were studied. The investigated calves were at 6 to 12 months of age and were belonged to three private farms in Dakahlia Governorate besides sporadic cases admitted to the Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Mansoura University, Egypt. Ten apparently healthy buffalo calves were also included as controls. According to the clinical outcome, the diseased calves were categorized into survivors (n = 11) and non-survivors (n = 9). Blood samples were collected from all animals to estimate blood gases besides a panel of selected biochemical parameters. The definitive diagnosis of dietary abomasal impaction was achieved by either left flank exploratory laparotomy or by necropsy. RESULTS: Both survivors and non-survivors demonstrated common clinical findings including distension of ventro-lateral aspect of the right abdomen, and varying degrees of dehydration. The great majority of survivors (81%) and 100% of non-survivors were anorexic and had rumen stasis as well as hard texture upon ballottement of the left flank. Approximately 45% of non-survivors had frothy salivation, expiratory grunting and were being tender when strong percussion was applied on the right flank. Diseased calves had metabolic alkalosis, while plasma potassium and chloride were significantly lower in non-survivors than those of survivors (P < 0.05). Serum malondialdehyde, superoxide dismutase and uric acid were significantly higher in diseased buffalo than controls and in non-survivors than survivors (P < 0.05). Serum total protein, albumin, creatinine, urea, aspartate aminotransferase, gamma-glutamyl transferase, and total bilirubin levels were also higher in non-survivors than those of survivors (P < 0.05). CONCLUSION: Buffalo calves with dietary abomasal impaction were associated with marked clinical and biochemical alterations that could be helpful for an accurate diagnosis of the disease.

The role of serum IL-17 and IL-6 as biomarkers of disease activity and predictors of remission in patients with lupus nephritis.

AIM: To determine the role of IL-17 and IL-6 in the pathogenesis of SLE as biomarkers of disease activity and predictors of remission and outcome of therapy in patients with active lupus nephritis. METHODS: The study was carried out on 72 SLE female patients and 70 sex- and age-matched normal healthy subjects as controls. SLE disease activity was assessed in all patients with (SLEDAI-2k scores). Plasma levels of IL-6, and IL-17 were measured by enzyme linked immunosorbent assay and their levels were correlated with clinical manifestations of the disease and (SLEDAI-2k). ROC curve analysis was performed to determine the validity of both cytokines in prediction of activity and remission of active lupus nephritis. RESULTS: SLE patients were found to have significantly higher levels of IL-17 (p<0.001) and IL-6 (p<0.001), in relation to normal subjects. Active group of patients had higher levels of both cytokines than the inactive one (P<0.001). Elevated serum levels of both cytokines were associated with active lupus nephritis, anemia and positively correlated with SLEDAI-2k scores (P=0.025 for IL-17 and P<0.001 for IL-6). There was a significant positive correlation between IL-6 and IL-17 serum concentrations during periods of disease activity (r=0.497, P=0.005) as well as during remission (r=0.662, P<0.001). ROC curve analysis for IL-6 and IL-17, as predictor of disease activity reviled, optimal cutoff level of 12.3 pg/ml and 19.7 pg/ml, with AUC=0.93, and 0.95, for both cytokines respectively, while as predictors of remission of active lupus nephritis, provide a cutoff value of IL-6 at 20.8 pg/ml, with AUC 0.80, and a cutoff value of IL-17 at 27.0 pg/ml, with AUC 0.82. CONCLUSION: In conjunction with their major role in pathogenesis of SLE, baseline serum levels of IL-6 and IL-17 can be used as sensitive biomarkers for disease activity, as well as predictors of remission of lupus nephritis.

Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats.

Cadmium is a non-essential toxic metal used in industrial process, causes severe risk to human health. Selenium (Se) is an essential trace mineral of fundamental importance for human health. Selenium has antioxidant enzymes roles and is needed for the proper function of the immune system. In this study, the protective effects of selenium against cadmium intoxication in rats have been investigated by monitoring some selective cytokines (IL-1ß, TNF α, IL-6, IL-10 and IFN-γ), antioxidant enzymes reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation malondialdehyde (MDA) as well as some selective biochemical markers of liver and kidney functions. Thirty-two rats were divided into four equal groups; the first group was used as a control. Groups 2-4 were treated with selenium (Se; 0.1mg/kg BW), cadmium (Cd; 40mg/L drinking water) and selenium plus cadmium, respectively. Rats were orally administered their relevant doses daily for 30 days. Blood samples were collected from heart puncture at the end of the experiment (30 days) for complete blood picture (CBC) and serum was separated to evaluate the different immunological parameters and biochemical parameters, as well as liver specimens for Cd and Se estimation. Rats in the Cd treated group have a significantly higher hepatic concentration of Cd than in other treated groups. Results revealed that cadmium significantly increased IL-1ß, TNF α, IL-6 and IL-10, beside peripheral neutrophils count, while the IFN-γ and lymphocytes were decreased in rat sera. In addition, GSH level, CAT, SOD and GPx activities were significantly decreased while lipid peroxidation (MDA) was increased. Regarding, liver and renal markers, they were significantly increased in the activities of aminotransferases (AST, ALT), urea and creatinine, while total plasma proteins and albumin were significantly decreased. On the other hand, selenium treated group, showed significantly increased IFN-γ, GSH level, CAT, and GPx activities, as well as lymphocyte count while IL-10 was decreased. Selenium in combination with cadmium, significantly improved the elevation of serum IL-1ß, IL-6, TNF α, IL-10 and malondialdehyde in addition to enhancing the antioxidant enzyme activities of GSH, CAT, GPx and SOD. Moreover, selenium has ameliorated the cadmium-induced liver and kidney damage by improving hepatic and renal markers. The results of this investigation demonstrated that selenium has the potential to countermeasure the immunosuppressive as well as hepatic and renal oxidative damage induced by cadmium in rats; selenium has shown promising effects against Cd toxicity.

Immunomodulatory effect of dietary Saccharomyces cerevisiae, beta-glucan and laminaran in mercuric chloride treated Nile tilapia (Oreochromis niloticus) and experimentally infected with Aeromonas hydrophila.

Six hundred and forty Nile tilapia (Oreochromis niloticus) weighing 80-100g were randomly allocated into eight equal groups (80 each). The first group acts as control. Groups S, B and L were fed on a ration supplemented with Saccharomyces cerevisiae, beta-glucans and laminaran, respectively for 21 days. Groups M, MS, MB and ML were subjected throughout the experiment to sublethal concentration of mercuric chloride (0.05 ppm). Gps. MS, MB and ML were fed on a ration containing S. cerevisiae, beta-glucan and laminaran respectively for 21 days. Fish were challenged with Aeromonas hydrophila (0.4 x 10(7) cells mL(-1)) via intra-peritoneal injection and the mortality rate was recorded up to 10 day post-challenge. The non-specific defense mechanisms, cellular and humoral immunity, beside the total and differential leukocytic count were determined. Lymphocyte transformation index, phagocytic activity percent, phagocytic index, total lymphocyte count, serum bactericidal activity and nitric oxide as well as the survival rate were insignificantly changed after 21 day in gps. MS&ML, when compared with mercuric chloride immune depressed group M. These parameters as well as the neutrophil adhesion, serum nitric oxide and survival rate were significantly increased in gp. MB when compared with gp. M. Meanwhile the cellular and humoral immunity beside the survival rate were significantly increased in groups S, B, L when compared with control group. It could be concluded that the whole yeast S. cerevisiae, beta-glucan and laminaran can be used as immunostimulants for the farmed Nile tilapia. The beta-glucans could be used in farmed Nile tilapia, under immune depressive stressful condition to increase their resistance to diseases.