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    Comparison of the chronic effects of ribavirin and caffeic acid phenethyl ester (CAPE) on pancreatic damage and hepatotoxicity
    (E-Century Publishing Corp, 2014) Motor, Sedat; Alp, Harun; Senol, Serkan; Pinar, Neslihan; Motor, Vicdan Koksaldi; Kaplan, Ibrahim; Alp, Ayse
    This study was aimed to comparison of the effects of the chronic use of the Ribavirin and caffeic acid phenethyl ester (CAPE) on the pancreatic damage and hepatotoxicity in rats. Methods: The rats were given orally 30 mg/kg/day doses of Ribavirin for 30 days, and intraperitoneally 10 mu mol/kg doses of CAPE. The 37 rats were divided into 4 groups: (I) Control (n=7), (II) Ribavirin (R) (n=10), (III) CAPE (n=10), and (IV) R+CAPE (n=10). Results: Ribavirin and CAPE yielded similar results in terms of Serum, total antioxidant status (TAS), total oxidant status (TOS), amylase, lipase, and insulin compared to the control group. However, while Ribavirin provided similar results with the control group in terms of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, the CAPE group had elevated AST and ALT levels compared to the control group. Histopathologic evaluations revealed that CAPE or Ribavirin had no degenerative effects on both the pancreas and liver tissues. In this way, the biochemical results were confirmed by the histopathologic results. Conclusion: It can be concluded that Ribavirin does not lead to any pancreatic damage and hepatotoxicity, and has more beneficial effects than CAPE on especially liver tissue.
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    Effects of intralipid and caffeic acid phenethyl ester on neurotoxicity, oxidative stress, and acetylcholinesterase activity in acute chlorpyriphos intoxication
    (E-Century Publishing Corp, 2014) Ozkan, Umit; Osun, Arif; Basarslan, Kagan; Senol, Serkan; Kaplan, Ibrahim; Alp, Harun
    Chlorpyriphos is one of the most widely used organophosphate (OP) insecticide in agriculture with potential toxicity. Current post-exposure treatments consist of anti-cholinergic drugs and oxime compounds. We studied the effects of intralipid and caffeic acid phenethyl ester (CAPE) on chlorpyriphos toxicity to compose an alternative or supportive treatment for OP poisoning. Methods: Forty-nine rats were randomly divided into seven groups. Chlorpyriphos was administered for toxicity. Intralipid (IL) and CAPE administered immediately after chlorpyriphos. Serum acetylcholinesterase (AChE) level, total oxidant status (TOS), total antioxidant response (TAR), and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immunohistochemical dyes were examined. Results: Serum enzym levels showed that chlorpyriphos and CAPE inhibited AChE while IL alone had no effect, chlorpyriphos and CAPE intensifies the inhibition effect. Significant difference at AChE levels between the chlorpyriphos+IL and chlorpyriphos+CAPE verified that IL has a protective effect on AChE inhibition. TAR levels were significantly increased in all groups except chlorpyriphos group, TOS levels revealed that CAPE and IL decrease the amount of oxidative stress. Histologic examination revealed that neuronal degeneration was slightly decreased at chlorpyriphos+IL group, but CAPE had a significant effect on protection of neuronal degeneration. Conclusion: The results of this study gave us three key points. 1) AChE activity is important for diagnosis of OP intoxication but it has no value for determining the neuro-degeneration. 2) CAPE inhibits AChE activity and may increase the muscarinic-nicotinic hyperactivation. Therefore it should not be used for treatment of OP intoxication. 3) IL decreases the severity of neurodegeneration and symptoms of OP intoxication and it can be used as a supportive agent.
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    Effects of intralipid and caffeic acid phenyl esther (CAPE) against hepatotoxicity and nephrotoxicity caused by glyphosate isopropylamine (GI)
    (Sage Publications Inc, 2016) Alp, Harun; Pinar, Neslihan; Dokuyucu, Recep; Kaplan, Ibrahim; Sahan, Mustafa; Senol, Serkan; Karakus, Ali
    This study was aimed to investigate the protective effects of caffeic acid phenyl esther (CAPE) and Intralipid (IL) against hepatotoxicity and nephrotoxicity caused by acute intoxication of glyphosate (N-phosphonomethyl) glycine) (GI) in rats. Forty-nine Wistar Albino rats were randomly divided into seven groups as: I, Control; II, Intralipid (IL) (18.6 mL/kg, orally); III, CAPE (10 mu mol/kg, intraperitoneally); IV, GI (4 mg/kg/day, intraperitoneally); V, GI + IL; VI, GI+CAPE; and VII, GI + IL + CAPE. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured in serum samples. Tissues were analyzed with hematoxylin and eosin (H&E) staining protocol. Bcl-2, Bax, and caspase-3 were evaluated by immunohistochemical method. The results revealed that, in hepatic tissues, the TAS levels were lower and the TOS levels were higher in the GI group compared to other groups. In renal tissues, the TAS levels were significantly lower in the GI group than in the control, IL, CAPE, and GI + IL + CAPE groups. The TOS levels were significantly higher in the GI group than in the control group. Moreover, histopathological analysis revealed severe hepatotoxicity in the GI group. In the GI + CAPE + IL group, hepatotoxicity recovered significantly. Nephrotoxicity was also observed in the GI group and moderately reduced in the GI + CAPE group. Biochemical results were confirmed by histopathologic examination. The results also revealed that CAPE and IL, due to their antioxidant effects, have a decreasing effect against both hepatotoxicity and nephrotoxicity caused by GI. Therefore, CAPE and IL may function as potential agents for supportive therapy since they decrease organ damage, or may facilitate the therapeutic effects of the routine treatment of patients with GI poisoning.
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    Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester (CAPE) on Hepatotoxicity and Pancreatic Injury Caused by Dichlorvos in Rats
    (Springer/Plenum Publishers, 2016) Alp, Harun; Pinar, Neslihan; Dokuyucu, Recep; Sahan, Mustafa; Oruc, Cem; Kaplan, Ibrahim; Senol, Serkan
    The present study was aimed to the investigate the protective effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity and pancreatic injury caused by acute dichlorvos (D) intoxication in rats. Forty-eight Wistar rats were randomly divided into seven groups each containing seven rats except control groups. The groups included control, D, CAPE, IL, D + CAPE, D + IL, and D + CAPE + IL. Total antioxidant status and total oxidative stress levels were measured by automated colorimetric assay. Tissues were evaluated using hematoxylin and eosin (H&E) staining. Tissues were analyzed with hematoxylin and eosin by using standard protocols. Also, Bcl-2, Bax and caspase-3 were evaluated by immunohistochemical method in liver tissue. Total oxidant status in control, CAPE, and IL groups were significantly lower, and total antioxidant status in the D + CAPE, D + IL, and D + IL + CAPE groups were significantly higher compared to the D group. CAPE and IL treatment decreased the apoptotic and mitotic cell count in liver tissue. Parenchymal necrosis caused by dichlorvos is observed in pancreas tissues of rats. Mild congestion and edema formation occurred in pancreas tissues following D + CAPE and D + IL therapies. These results indicate that CAPE and IL have the potential to decrease oxidative stress and hepatic and pancreatic injuries caused by acute dichlorvos intoxication. These drugs can be considered as a new method for supportive and protective therapy against pesticide intoxication.
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    Protective Effects of Intralipid and Caffeic Acid Phenyl Esther (CAPE) on Neurotoxicity Induced by Ethanol in Rats
    (Turkish Neurosurgical Soc, 2017) Basarslan, Seyit Kagan; Osun, Arif; Senol, Serkan; Korkmaz, Murat; Ozkan, Umit; Kaplan, Ibrahim
    AIM: Ethanol causes oxidative degradation of the mitochondria! genome in the brain. This effect could contribute to the development of brain injury in some alcoholic patients. We investigated the protective effect of caffeic acid phenyl esther (CAPE) and intralipid (IL) on oxidative stress and neurotoxicity induced by ethanol intake. MATERIAL and METHODS: The forty-eight rats were randomly divided into seven groups. Ethanol was administered for acute toxicity. IL and CAPE were administered immediately after ethanol intake. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative status index (OSi) were evaluated and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immuno-histochemical dyes was performed. RESULTS: In the ethanol group, TAS levels were significantly lower than the other groups and this finding indicates that the toxic effect of ethanol reduces antioxidant levels. In the ethanol group, TOS levels were significantly higher than the other groups. These results showed that ethanol induced oxidative stress. IL treatment increased TAS levels, and CAPE decreased TOS levels against ethanol toxicity. There was correlation between TAS and TOS levels. Also, histopathologic results confirmed these biochemical results. CONCLUSION: CAPE and IL treatment could be effective course of therapy to enhance therapeutic efficacy and may provide a promising approach for the treatment of neurotoxicity and oxidative stress induced by ethanol in clinic.