Lactoferrin Enhanced Apoptosis and Protected Against Thioacetamide-Induced Liver Fibrosis in Rats

BACKGROUND: Liver fibrosis is the common pathologic consequence of all chronic liver diseases.AIM: Lactoferrin (Lf) was investigated for its possible hepatoprotective effect against thioacetamide (TAA)-induced liver fibrosis rat model.MATERIAL AND METHODS: Rats received TAA (200 mg/kg/biweekly, ip) for four successive weeks. Lf (200 mg/kg/day, p.o.) or vehicle (VHC) was administered for one month before and another month during TAA injection. Body weight and mortality rate were assessed during the month of TAA-intoxication. Thereafter, serum and liver tissues were analyzed for liver function, oxidative, fibrotic and apoptotic markers.RESULTS: Lf conserved rats against TAA-induced body weight-loss and mortality. Preservation of serum albumin, alkaline phosphatase and total bilirubin levels was also observed. Lf also protected rats against TAA-induced decrease in reduced glutathione and increase in malondialdehyde liver contents. Normal liver contents of hydroxyproline, nuclear factor kappa B and alpha fetoprotein; as markers of fibrosis; were increased with TAA and conserved with Lf-TAA. Lf maintained the normal architecture of the liver and immunohistochemical findings revealed increase in apoptotic bodies compared to TAA that favored necrosis.CONCLUSION: In conclusion, Lf improved liver function, reduced oxidative stress and liver fibrosis, and enhanced apoptosis in rats with liver fibrosis, suggesting it to have useful therapeutic potential in patients with liver fibrosis

Protective Effects of the Third Generation Vasodilatory Î’eta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS).AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats.MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-кB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed.RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment.CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties

The impact of homocysteine level on methotrexate induced neurotoxicity in children treated with St. Jude total XV acute lymphoblastic leukemia protocol

Purpose: Methotrexate (MTX) is an antimetabolite that is routinely used in the treatment of hematological malignancies and during its metabolism leads to hyperhomocysteinemia that is associated with neurotoxicity. The purpose of this prospective study is to determine whether the increase in plasma homocysteine (Hcy) concentration is related to MTX-induced neurotoxicity.Methods: We investigated these changes for both newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) pediatric patients treated at the National Cancer Institute, Egypt. They were treated according to St. Jude total XV protocol to receive 2.5 or 5 g/m2 MTX as a phase of consolidation and were selected between October 2009 and January 2010.Results: Twenty-nine patients were analyzed, M/F: 20/9, the mean age was 8 +/- 4.4 years. Hcy level above 15 µmol/L was considered positive. Hcy levels mean at diagnosis, pre 1st HD MTX, post 1st HDMTX, Pre 2nd HDMTX, Post 2nd HDMTX were 12.10 µmol/L ± 4.17, 6.90 µmol/L ± 3.02, 17.59 µmol/L ± 6.00, 7.21 µmol/L ± 2.73 and 13.74 µmol/L ± 4.75 respectively. Seventeen patients (58%) had features suggestive of neurotoxicity. Positive Hcy levels were associated with neurotoxicity p = 0.05, higher HDMTX 5 g/m2 P= 0.023. A highly significant relation was found between initial Hcy level at diagnosis and final Hcy level p = 0.001; the same as between Hcy level Post 1st HDMTX and that Post 2nd HDMTX with p = 0.006.Conclusion: plasma Hcy concentration was significantly elevated after HDMTX administration and this elevation is associated with the observed neurotoxicity. Whether the elevation in Hcy concentration can prove an informative biomarker for neurotoxicity requires additional testing with other MTX regimens

Protective Effects of Vasodilatory Î’eta-Blockers Carvedilol and Nebivolol against Glycerol Model of Rhabdomyolysis-Induced Acute Renal Failure in Rats

BACKGROUND: Rhabdomyolysis (RM)-induced acute renal failure (ARF) accounts for about 10–40% of all cases of ARF.AIM: The present study investigated the possible protective effect of two nitric oxides (NO)-releasing third generation β-blockers, carvedilol (Carv) and nebivolol (Nebi), against RM-mimicking glycerol (Gly)-induced ARF in rats.MATERIAL AND METHODS: After 24 h dehydration, rats received a single dose of 50% Gly (8 ml/kg, im). They were treated with vehicle, Carv (2.5 mg/kg/day, po) or Nebi (10 mg/kg, po) for 3 successive days starting from an hour prior to Gly injection. Evaluation of blood pressure and locomotor activity was performed during the experiment. 72 h following Gly administration, total protein in the urine, serum levels of creatinine, blood urea nitrogen, sodium and potassium as well as the renal contents of malondialdehyde, reduced glutathione and NO were assessed, together with a histopathological examination of renal tissues.RESULTS: Carv and Nebi attenuated Gly-induced renal dysfunction and histopathological alterations. They decreased the Gly-induced oxidative stress and increased renal NO concentration. Restoration of normal blood pressure and improvement of locomotor activity were also observed.CONCLUSION: The results clearly demonstrate protective effects of Carv and Nebi against renal damage involved in RM-induced ARF and suggest a role of their antioxidant and NO-releasing properties

ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

The impact of homocysteine level on methotrexate induced neurotoxicity in children treated with St. Jude total XV acute lymphoblastic leukemia protocol

Purpose: Methotrexate (MTX) is an antimetabolite that is routinely used in the treatment of hematological malignancies and during its metabolism leads to hyperhomocysteinemia that is associated with neurotoxicity. The purpose of this prospective study is to determine whether the increase in plasma homocysteine (Hcy) concentration is related to MTX-induced neurotoxicity.Methods: We investigated these changes for both newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) pediatric patients treated at the National Cancer Institute, Egypt. They were treated according to St. Jude total XV protocol to receive 2.5 or 5 g/m2 MTX as a phase of consolidation and were selected between October 2009 and January 2010.Results: Twenty-nine patients were analyzed, M/F: 20/9, the mean age was 8 +/- 4.4 years. Hcy level above 15 µmol/L was considered positive. Hcy levels mean at diagnosis, pre 1st HD MTX, post 1st HDMTX, Pre 2nd HDMTX, Post 2nd HDMTX were 12.10 µmol/L ± 4.17, 6.90 µmol/L ± 3.02, 17.59 µmol/L ± 6.00, 7.21 µmol/L ± 2.73 and 13.74 µmol/L ± 4.75 respectively. Seventeen patients (58%) had features suggestive of neurotoxicity. Positive Hcy levels were associated with neurotoxicity p = 0.05, higher HDMTX 5 g/m2 P= 0.023. A highly significant relation was found between initial Hcy level at diagnosis and final Hcy level p = 0.001; the same as between Hcy level Post 1st HDMTX and that Post 2nd HDMTX with p = 0.006.Conclusion: plasma Hcy concentration was significantly elevated after HDMTX administration and this elevation is associated with the observed neurotoxicity. Whether the elevation in Hcy concentration can prove an informative biomarker for neurotoxicity requires additional testing with other MTX regimens.</p

Protection by low-dose γ radiation on doxorubicin-induced nephropathy in rats pretreated with curcumin, green tea, garlic or l-carnitine

The protective potentials of a single exposure to 0.3 Gy of γ radiation alone or with previous treatment with certain natural products with antioxidants activity, namely curcumin (50 mg/kg, i.p.), green tea (300 mg/kg, p.o.), garlic (100 mg/kg, p.o.) or l-carnitine (40 mg/kg, i.p.) against doxorubicin (DOX)-induced nephropathy in rats were studied. Natural products were administered daily for 14 successive days followed by single i.p. injection of DOX (5 mg/kg). Rats were subjected to whole body γ radiation, 1 day before DOX administration. Serum levels of creatinine, urea, uric acid, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterols, total proteins and albumin as well as renal concentrations of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and calcium (Ca) were determined. Irradiation provided significant protections against DOX-induced changes in all measured parameters, except renal Ca content. All the test natural products significantly improved radiation-induced protection against renal lipid peroxidation. l-Carnitine markedly augmented the protection toward changes in renal GSH, NO and Ca concentrations. Curcumin increased the protection toward changes in serum albumin and renal GSH and NO concentrations, while garlic increased the protection toward changes in serum LDL-C level. It could be concluded that low-dose γ radiation could provide prophylaxis against DOX-induced nephropathy which might be augmented by the use of certain natural antioxidants

Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats

Myocardial infarction (MI) continues to be a major public health problem in the world. Statins exhibit cardio-protective effects by several mechanisms beyond their lipid lowering activity. Quercetin is a natural flavonoid that possesses significant anti-oxidant and antiinflammatory activities. The present study aimed to investigate the effects of pretreatment with atorvastatin (10 mg/kg) and quercetin (50 mg/kg), as well as their combination on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), as well as oxidative stress and inflammatory biomarkers including serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) as well as cardiac contents of lipid peroxides, reduced glutathione (GSH), and nitrite. Furthermore, ECG monitoring and histological examinations of cardiac tissues were done. Isoprenaline increased serum CK-MB activity and cTn-I level as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart tissues. Pretreatment with atorvastatin suppressed significantly the elevated levels of cTn-I, CRP, TNF-α, and IL-10 in serum coupled with reduction in cardiac lipid peroxides; however, it increased cardiac nitrite content. Quercetin decreased isoprenaline-induced changes in oxidative stress and inflammatory biomarkers with marked improvement in ECG and histopathologic alterations. Combination of quercetin with atorvastatin resulted in similar protective effects. In conclusion, quercetin can be regarded as a promising cardio-protective natural agent in MI alone or combined with atorvastatin

Isoprenaline-Induced Myocardial Infarction in Rats: Protective Effects of Hesperidin

Myocardial infarction is amongst the most common causes of death worldwide. The present study aimed to investigate the cardioprotective effect of hesperidin (200 mg/kg) either individually or in combination with atorvastatin (10 mg/kg), as a reference standard, in isoprenaline-induced myocardial infarction in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), oxidative stress biomarkers including cardiac contents of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) as well as serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). Furthermore, ECG monitoring and histologic examinations of cardiac tissues were done. Isoprenaline increased CK-MB activity as the well the levels of cTn-I, inflammatory and oxidative stress biomarkers. In addition, it produced ST segment elevation and degenerative changes in heart tissues. The obtained data revealed that pretreatment with hesperidin alone or in combination with atorvastatin significantly decreased the elevated activity of serum CK-MB as well as serum levels of cTn-I, CRP, TNF-α and IL-10 coupled by a reduction in cardiac lipid peroxides and NO content. Moreover, both treatments resulted in marked improvement in isoprenaline-induced ECG and histopathologic changes. In conclusion, hesperidin can be regarded as a promising cardioprotective natural agent in myocardial infarction when used alone or combined with atorvastatin