Prophylactic role of α-lipoic acid and vitamin E against zinc oxide nanoparticles induced metabolic and immune disorders in rat's liver.

OBJECTIVES: Potential health hazard is associated with the wide use of nanoparticles. The prophylactic role of either α-lipoic acid (α-lip) or vitamin E (vit E) against the toxic effect of zinc oxide nano-particles (ZnO-NPs) induced metabolic disorder, inflammation and DNA damage in rat livers was studied. MATERIALS AND METHODS: ZnO-NPs were administered orally using two doses (600 mg and 1 g/kg body weight/day for 5 conscutive days). Some biomarkers of tissue damage, metabolic disorder, and DNA damage were investigated to explore the protective mechanisms of α-lip or vit E against ZnO-NPs induced hepatotoxicity. RESULTS: Co-administration of either α-lip (200 mg/kg body weight) or vit E (100 mg/kg body weight) daily for three weeks to ZnO-NPs intoxicated rats, significantly down-modulated the marked increase in serum ALT (marker of liver damage) and also serum glucose level (marker of metabolic disorder) as well as the pro-inflammatory biomarkers including nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and immunoglobin G (IGg). Reduced glutathione level was decreased while caspase3 level was elevated in liver tissues of ZnO-NPs treated group compared with intoxicated one. Moreover histopathological examination of liver tissue supported the previous biochemical markers. Furthermore, ZnO-NPs induced hepatic oxidative DNA damage. CONCLUSIONS: Either α-lip or vit E proved to be hepatoprotective agents against ZnO-NPs toxicity because they ameliorated metabolic and immune disorders related to liver damage and modulated the previous measured parameters.

Potential impact of silymarin in combination with chlorogenic acid and/or melatonin in combating cardiomyopathy induced by carbon tetrachloride.

The aim of this study was to investigate the effective role of silymarin either alone or in combination with chlorogenic acid and/or melatonin against the toxic impact of carbon tetrachloride (CCl4) induced cardiac infarction. CCl4 (l.2 ml/kg body weight) was administered as a single dose intraperitoneally. The results revealed that the administration of silymarin alone or in combination with chlorogenic acid (CGA) and/or melatonin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated the increases in serum markers of cardiac infarction, including troponin T and creatine kinase-MB (CK-MB), as well as increases in the pro-inflammatory biomarkers, including interleukin-6 (IL-6), interferon-γ (IFN-γ) in serum and tumor necrosis factor-α (TNF-α) and C-reactive protein in cardiac tissue compared to CCl4 intoxicated rats. The used agents also successfully modulated the alteration in vascular endothelial growth factor (VEGF) in serum and the oxidative DNA damage and the increase in the apoptosis marker caspase 3 in cardiac tissue in response to CCl4 toxicity. The present biochemical results are supported by histo-pathological examination. The current results proved that treatment with silymarin in combination with CGA and melatonin was the most effective one in ameliorating the toxicity of CCl4 induced cardiac damage and this may support the use of this combination as an effective drug to treat cardiac damage induced by toxic agents.

Potential impact of quercetin and idebenone against immuno- inflammatory and oxidative renal damage induced in rats by titanium dioxide nanoparticles toxicity.

The aim of this study was to investigate the toxic impacts of titanium dioxide nanoparticles (TiO2-NPs) on rat kidneys and the possible prophylactic role of either quercetin or idebenone. TiO2-NPs were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days to evaluate dose-dependent toxicity referred to the OECD guidelines for testing of chemicals. The results showed that administration of either low or high repeated doses of TiO2-NPs to rats significantly increases serum kideney function biomarkers (urea, creatinine and uric acid) as well as increases in serum glucose and serum immuno- inflammatory biomarkers including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), immunoglobin g (IGg), vascular endothelial growth factor (VEGF, angiogenic factor) and nitric oxide (NO) with a concomitant decrease in renal GSH content versus normal control values. The increase in these biomarkers was more evident in rats intoxicated with high TiO2-NPs repeated doses. Oral co- administration of either quercetin or idebenone (each 200mg/Kg body weight) daily for three weeks to rats intoxicated by either of the two doses markedly ameliorated TiO2-NPs induced alteration in the above biomarkers. The prophylactic impacts of both agents on biochemical markers were more pronounced in rats received low TiO2-NPs repeated doses. The biochemical investigation was supported by histological examination. In conclusion, The data showed the severity in renotoxicity of TiO2-NPs was dose-dependent and the protective effect of quercetin and idebenone may be related to their antioxidant and anti-inflammatory properties.

Induction of inflammation, DNA damage and apoptosis in rat heart after oral exposure to zinc oxide nanoparticles and the cardioprotective role of α-lipoic acid and vitamin E.

Although zinc oxide nanoparticles (ZnO-NP) are being used on a wide scale in the world consumer market, their potential hazards on humans remain largely unknown. The present study was aimed at investigating the oral toxicity of ZnO-NP in 2 dose regimen (600 mg/kg and 1 g/kg body weight for 5 consecutive days) in rats. In addition, the protective role of either α-lipoic acid (Lipo) or vitamin E (Vit E) against this cardiotoxic effect of ZnO-NPs was assessed. Results revealed that, co-administration of Lipo (200 mg/Kg body weight) or Vit E (100 mg/Kg body weight) daily for 3 weeks to rats intoxicated with ZnO-NPs (in either of the 2 dose regimen) significantly ameliorated the cardiotoxic effect of these nanoparticles. As, both agents significantly reduced the increase in serum cardiac injury markers including troponin-T, creatine kinase-MB (CK-MB), and myoglobin. Additionally, Lipo and Vit E significantly decreased the increase in serum pro-inflammatory biomarkers level including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP). Moreover, either of the 2 used agents successfully alleviated the alteration in nitric oxide (NO) and vascular endothelial growth factor (VEGF) in ZnO-NPs in sera of intoxicated group. They also significantly reduced the increase in cardiac calcium concentration and the consequent oxidative deoxyribonucleic acid (DNA) damage, as well as the increase in cardiac caspase-3 activity of intoxicated rats. Conclusively, these results indicate that early treatment with either α-lipoic acid or vitamin E may offer protection against cardiac tissue injury induced by the deleterious toxic impacts of ZnO-NPs.

New role of antinutritional factors, phytic acid and catechin in the treatment of CCl4 intoxication.

Both phytic acid (PA) and catechin (CA) are well known antioxidants of natural origin. They were frequently tried on experimental level as hepatoprotectants, relying only on their antioxidant properties. The present study was conducted mainly to outline the other biochemical pathways underlying the hepatotherapeutic potential of both drugs and to check a possible synergistic action if prescribed concomitantly. As both materials are frequently taken on a daily basis in food and drinks, it will be helpful to pursue their possible utility and/or to check if their value is really of medical importance. For this purpose, CCl(4) was used as a hepatotoxin, we evaluated plasma total sialic acid (TSA), serum ascorbic acid (AA) levels, liver tissue thiobarbituric acid reactive species (TBARS) as a marker for lipid peroxidation and total protein (TP) content as a rough marker to measure hepatic synthetic capability in 80 male Wistar rats as experimental models. Animals were classified into 8 groups (10 rats each), the first as control, the second as PA treated (0.3 mg kg (-1)), orally, the third as CA treated (30 mg kg (-1)) intraperitoneally, the fourth given both drugs, as a single daily dose for 2 weeks. The same design was repeated 24 hours after CCl(4)-intoxication (1mL kg (-1)), intraperitoneally, as a single dose. The results revealed that both PA and CA when used individually, significantly down-regulated TSA in both physiologic (no CCl(4 )treatment) and pathologic (CCl(4)- intoxication) states accompanied by significant decrease in lipoperoxidation. The therapeutic action against TSA and the antioxidant power were abolished by co-administration of both drugs . AA was only decreased by PA and the combination in the physiologic state. Both PA and CA showed significant therapeutic effect for protein synthesis against CCl(4)-intoxication, but the combination abolished this effect. We conclude that both drugs can be considered as a chemotherapeutic against hepatopathies and we for the first time contraindicate the concomitant use of both drugs.

Oxidative stress, lipid profile and liver functions in average Egyptian long term depo medroxy progesterone acetate (DMPA) users.

Depo-medroxy progesterone acetate (DMPA, Depo-Provera) is used in more than 80 countries as a long-acting contraceptive administered as a single intramuscular(i.m) injection of 150 mg/3 months. The present study was set up to investigate the effects of DMPA on 80 average Egyptian women classified into four groups comprising those using the drug for one, two, three and four years, respectively, compared to a control group (N = 20) of married non-hormonally - treated women of similar ages. The drug showed a transient significant elevation of alanine aminotransferase activity (ALT)without an apparent effect on other liver indices, namely total bilirubin (T.Bil) level,aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities. Only the low density/high density lipoproteins cholesterol ratio (LDLC/HDLC) was gradually and non-significantly (ns) increased in comparison to control group, however, neither total cholesterol (TC) nor triglycerides (TG) were affected by the drug. The lipid peroxide product malondialdehyde (MDA) was significantly elevated in an gradual manner with a corresponding decrease in reduced glutathione (GSH), without any change in blood nitric oxide (NO) levels. It can be concluded that DMPA may be considered as a safe contraceptive medication for the studied group of women, but that special care should be exercised for cardiovascular, hepatic and other patients more sensitive to the harmful effects of free radicals. Alternatively, supportive medications are advisable for each exposed case to secure against the possible irreversible adverse effects of the drug by continuous use. In addition, annual re-evaluation is much more advisable despite the proven safety of the drug.