Résumé
ABSTRACT Acetaminophen (APAP) is a widely-used analgesic, while toxic doses of which induce liver injury. Inducible cyclooxygenase-2 (COX-2) is derived prostaglandins which play an anti-inflammatory role in acetaminophen-induced hepatotoxicity. Selective activation of vascular endothelial growth factor (VEGFR1, flt -1) on endothelial cells increased mRNA levels of hepatocyte mitogens (IL-6) and hepatocyte growth factor leading to prosurvival effects on hepatocytes. The aim of this study was to compare the hepatoprotective effect of N-acetylcysteine (NAC; the antidote for APAP) with that of α-Lipoic acid (ALA) and/or Thymoquinone (THQ) either alone or in combination on liver injury induced by APAP. APAP administration elevated most of the previously measured parameters and decreased GSH, SOD, and total protein levels compared with the control group. Liver sections of H&E demonstrate liver injury characterized by centrilobular hepatocellular necrosis, COX-2, and flt-1 expressions were also increased. Treatment with all fore mentioned antioxidants ameliorated most of the altered parameters compared to APAP-treated group. Treatment with the combination of ALA and THQ was the most effective therapy in the attenuation of liver injury assessed by a decrease in ALT and ALP activities and down-regulation of COX-2 and flt-1 expression. Section of liver from rat received APAP, ALA and THQ shows a marked improvement of hepatic degeneration which restricted to few hepatocytes with mild vacuolation of their cytoplasm while the nuclei appear normal mimic to control cells. It was concluded that the natural antioxidants such as ALA and THQ, may be considered as a potential antidote in combating liver injury induced by APAP.
Résumé
This study aimed to explore the effective role of carnosine and /or L- arginine in down regulation of the inflammatory molecule expression caused renal damage in response to sodium nitrite (NaNO2) induced hypoxia in rats . NaNO2 was administered subcutaneously (s.c.) to rats as a single dose (60 mg/kg body weight ). L-arginine (200mg/Kg body weight) and carnosine (250 mg/ Kg body weight ) were administered (i.p.) as a single dose , 24 h before NaNO2 injection. The results revealed that pre- administration of arginine and /or carnosine to NaNO2 hypoxic rats, significantly modulated the increases in serum markers of renal function (creatinine and urea) as well as the decrease in hemoglobin (Hb) level versus hypoxic rats. The two agents each alone or in a combination, markedly down regulated the serum pro-inflammatory molecules, including tumor necrosis factor-α (TNF- α) , C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and heat shock protein -70 (HSP-70) as well as interleukin-6 (IL-6) in renal tissue compared to NaNO2 hypoxic rats . Also, the two agents successfully down modulated the alteration in the serum hypoxia inducible factor 1α (HIF 1α) . The present biochemical results were also supported by histopathological examination. In conclusion, the current data revealed that although the efficacy of arginine or carnosine each alone, their combination was more effective in ameliorating the renal damage induced by inflammatory molecules in response to NaNO2 hypoxia . This may support the use of this combination as an effective drug to treat hypoxic renal damage
Résumé
The objective of this study is to examine whether silymarin alone or in combination with chlorogenic acid and/ or melatonin plays a modulatory role against apoptotic damage in rats liver induced by of CCl4. The present work revealed that CCl4 induced elevation of in Bax, Smad, TGF-β and NFkBhepatic mRNA expression, administration of silymarin alone down regulates these expressions. Treatment with chlorogenic acid and/ or melatonin along with silymarin produced best results in this concern. Bcl-2 expression was down regulated by CCl4 whereas concurrent treatment of chlorogenic acid and/ or melatonin along with silymarin increased this expression. On conclusion, the use of chlorogenic acid and/ or melatonin potentiates the anti-apoptotic action of silymarin.
Résumé
ABSTRACT The aim of this study was to investigate the effective role of silymarin either alone or in a combination with vitamin E and/or curcumin against the toxic impact of carbon tetrachloride (CCl4) induced liver injury The results revealed that administration of silymarin alone or in a combination with vitamin E and/or curcumin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated DNA damaged and apoptosis markers in rat livers, proinflammatory markers including tumor necrosis factor- α (TNF- α) and C-reactive protein (CRP ) in rat livers as well as interleukin 6 (IL-6), interferon gamma (IFN-γ) and vascular endothelial growth factor (VEGF) in rat sera. These treatments also could ameliorated the alteration in cytochrome P450 2E1 (CYP2E1) activity in livers of CCl4 intoxicated rats as well as the increase in the serum alanine aminotransferase (ALT) compared with CCl4 intoxicated untreated rats. The present biochemical results are supported by histo-pathological examination. In conclusion, silymarin in a combination with vitamin E and curcumin was the most effective treatment in alleviating CCl4 induced liver damage and this may support the use of this combination as an effective treatment against liver damage induced by toxic agents.
Résumé
The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2) and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs.