Vitamin D Ameliorates the Hepatic Oxidative Damage and Fibrotic Effect Caused by Thioacetamide in Rats.

Vitamin D3 (VD3) is a sunshine hormone that regulates cellular proliferation, differentiation, apoptosis, and angiogenesis related to liver parenchyma. We used a thioacetamide (TAA)-induced hepatic fibrosis rat model in our study to investigate the beneficial roles of VD3 to overcome extensive liver fibrosis. Randomly, four equal groups (eight rats per group) underwent therapy for eight successive weeks: a control group, a group treated with TAA 100 mg/kg BW IP every other day, a group treated with VD3 1000 IU/kg BW IM every day, and a TAA+VD group treated with both therapies. Treatment with VD3 after TAA-induced hepatic fibrosis was found to alleviate elevated liver function measures by decreasing ALT, AST, and ALP activity; decreasing total bilirubin, direct bilirubin, cholesterol, and triglyceride levels; and increasing glucose and 25[OH]D3. Rats treated with VD3 showed marked decreases in MDA and increased SOD, CAT, and GSH levels. In addition, CD34 and FGF23 gene expressions were reduced after dual therapy. Liver sections from the TAA+VD group showed markedly decreased hepatic lesions, and Masson's trichrome stain showed a marked decrease in dense bluish-stained fibrous tissue. The immunohistochemical expression of TGF-ß and α-SMA showed markedly decreased positive brown cytoplasmic expression in a few hepatocytes, clarifying the antifibrotic effect of VD3 in hepatic fibrosis. In conclusion, VD3 alleviates hepatotoxicity and fibrosis caused by TAA.

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress, inflammation and apoptosis in rats.

OBJECTIVE: Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats. METHODS: In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1ß (IL-1ß), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5'-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers. RESULTS: Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1ß, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group. CONCLUSION: This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.

Enhanced renoprotective actions of Paricalcitol and omega-3 fatty acids co-therapy against diabetic nephropathy in rat.

Introduction: Although the synthetic vitamin D analogue, Paricalcitol, and omega-3 Fatty acids (ω-3) alleviated diabetic nephropathy (DN), their combination was not previously explored. Objectives: This study measured the potential ameliorative effects of single and dual therapies of Paricalcitol and/or ω-3 against DN. Methods: Forty rats were assigned as follow: negative (NC) and positive (PC) controls, Paricalcitol, ω-3 and Paricalcitol + ω-3 groups. Diabetes was generated by high-fat/high-fructose diet and a single streptozotocin injection (40 mg/kg). DN was confirmed by raised fasting blood glucose (FBG), polyuria, proteinuria, and decreased urine creatinine levels. Paricalcitol intraperitoneal injections (0.25 µg/Kg/day; 5 times/week) and oral ω-3 (415 mg/kg/day; 5 times/week) started at week-9 and for eight weeks. Results: The PC group showed hyperglycaemia, dyslipidaemia, abnormal renal biochemical parameters, elevated caspase-3 expression, and increased apoptosis by TUNEL technique. The mRNAs and proteins of the pathogenic molecules (TGF-ß1/iNOS) and markers of tissue damage (NGAL/KIM-1) augmented substantially in the PC renal tissues relative to the NC group. The oxidative stress (MDA/H2O2/protein carbonyl groups) and pro-inflammatory (IL1ß/IL6/TNF-α) markers increased, whereas the anti-inflammatory (IL10) and anti-oxidative (GSH/GPx1/GR/SOD1/CAT) declined, in the PC renal tissues. The monotherapy groups were associated with ameliorated FBG, lipid profile and renal functions, and diminished TGF-ß1/iNOS/NGAL/KIM-1/Caspase-3 alongside the apoptotic index than the PC group. The oxidative stress and pro-inflammatory markers decreased, whilst the anti-oxidative and anti-inflammatory molecules escalated, in the monotherapy groups than the PC group. Although the Paricalcitol renoprotective actions were better than ω-3, all the biomarkers were abnormal than the NC group. Alternatively, the Paricalcitol + ω-3 protocol exhibited the best improvements in metabolic control, renal functions, oxidative stress, inflammation, and apoptosis. However, FBG and tissue damage were persistently higher in the co-therapy group than controls. Conclusions: Both monotherapies showed modest efficacy against DN, whereas their combination displayed boosted renoprotection, possibly by enhancing renal anti-oxidant and anti-inflammatory pathways.

Immunomodulatory Effect of Vitamin C on Proinflammatory Cytokines Production in Ossimi Lambs (Ovis aries) with Pneumonic Pasteurellosis.

In this study, we have investigated the impact of vitamin C on the production of pro-inflammatory cytokines (interleukin 1 ß (IL-1 ß), interleukin 6 (IL-6), interleukin 12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α)) in lambs naturally infected by pneumonic pasteurellosis. Of 37 lambs, 18 lambs were identified to have pneumonic pasteurellosis and randomly allocated into two equal groups. Single subcutaneous dose of tulathromycine alone (2.5 mg kg-1) or tulathromycine combined with vitamin C (3 gm kg-1) were administrated to the diseased lambs. The serum levels of IL-1ß, IL-6, IFN-γ, and TNF-α were returned to the normal levels in pneumonic lambs treated with the combination therapy. The obtained results indicate the selective influences of vitamin C on pro-inflammatory cytokines production in sera of lambs with pneumonic pasteurellosis and highlights the value of vitamin C as a potential anti-inflammatory drug and ideal immunomodulatory agent.

Dietary supplementation of guanidinoacetic acid improves growth, biochemical parameters, antioxidant capacity and cytokine responses in Nile tilapia (Oreochromis niloticus).

A total of 180 unsexed Nile Tilapia fish (initial weight, 21 g) fed isonitrogenous (32%), isocaloric (3000 kcal/kg) diets containing different levels of guanidinoacetic acid (GAA) at levels of (GAA1, 0.06%, GAA2, 0.12%, GAA3, 0.18%); for 60 days. Results showed higher final body weight (FBW) and body weight gain (BWG) in groups supplemented with different levels of GAA. Specific growth rate (SGR) was the highest in groups supplemented with 0.12% and 0.18% GAA. Lipid % of whole-body composition was higher in all groups excluding GAA3 group. Serum creatine kinase (CK) activity, cholesterol, and creatinine levels showed a marked significant (P < 0.05) increase in all GAA supplemented groups compared to the control one. Triglycerides level demonstrated a higher elevation (P < 0.05) in both GAA2 and GAA3 supplemented groups. No significant observed in total protein, albumin, globulin, and A/G ratio. Lipid peroxidation marker (malondialdehyde/MDA) is markedly decreased along with a significant increase of superoxide dismutase (SOD), reduced glutathione (GSH), and nitric oxide (NO) levels in both GAA2 and GAA3 compared to other groups. Similarly, interleukin 1ß (IL-1ß) and tumor necrosis factor (TNF-α) gene expression levels were downregulated along with upregulation of transforming growth factor ß1 (TGF-ß1) at higher GAA levels, particularly at 0.18%. Our findings give important insights for the growth promoting, antioxidant and immunomodulatory effects of GAA supplemented diet particularly at level of 0.18%.

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.