The aim of this study was to investigate the possible protective role of caffeic acid phenethyl ester on testicular toxicity of methotrexate in rats. Nineteen male rats were divided into three groups as follows: group I, control; group II, methotrexate-treated; group III, methotrexate + caffeic acid phenethyl ester-treated. In the second day of experiment, a single dose of methotrexate was intraperitoneally administered to groups II and III, although a daily single dose of caffeic acid phenethyl ester was intraperitoneally administered to group III for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. In the tissue, the level of lipid peroxidation as malondialdehyde and activities of superoxide dismutase were higher in the methotrexate group than in the control group. Lipid peroxidation levels and superoxide dismutase activities were decreased in caffeic acid phenethyl ester + methotrexate group compared with methotrexate group. The activities of catalase in the methotrexate group decreased insignificantly although its activities were significantly increased by caffeic acid phenethyl ester administration. The activity of glutathione peroxidase did not change in the groups. There was significant difference in body weight between control and methotrexate-induced groups. In conclusion, the administration of methotrexate causes elevation of oxidative stress although treatment with caffeic acid phenethyl ester has protective effects on the oxidative stress in testes.

The exact mechanisms of methotrexate-induced renal toxicity have not yet been determined. However, several hypotheses have been put forward, including oxidative stress. The aim of this study was to investigate the role of caffeic acid phenethyl ester (Caffeic Ester), a novel antioxidant, on methotrexate-induced renal oxidative stress in rats. Nineteen adult male rats were equally divided into three experimental groups as follows: control group, methotrexate-treated group, and methotrexate+Caffeic Ester-treated group. A single dose of methotrexate (20 mg/kg) was administered intraperitoneally (ip). Caffeic Ester (10 micromol/kg) was administered ip, once daily for seven days. Malondialdehyde (MDA) levels (an index of lipid peroxidation) were used as a marker of oxidative stress-induced renal injury. Similarly, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined to evaluate the changes of antioxidant status in renal tissue. Methotrexate administration to control rats increased MDA levels (P<0.0001), but decreased SOD, CAT and GSH-Px activities in renal tissue (P<0.0001). Caffeic Ester+ methotrexate treatment caused a significant decrease in MDA levels (P<0.001), and caused an increase in SOD, CAT and GSH-Px activities when compared with methotrexate treatment alone (P<0.001, <0.05, <0.0001, respectively). In conclusion, methotrexate leads to a reduction in antioxidant enzymatic defense capacity and causes lipid peroxidation in renal tissue. Similarly, Caffeic Ester exhibits protective effects on methotrexate-induced renal oxidative impairment in rats.

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Methotrexate (MTX), a folic acid antagonist, is widely used as a cytotoxic chemotherapeutic agent. MTX-associated neurotoxicity is an important clinical problem. The aim of this study was to investigate the role of caffeic acid phenethyl ester (CAPE) on cerebellar oxidative stress induced by MTX in rats. A total of 19 adult male rats were divided into three experimental groups as follows: MTX group (MTX treated), MTX+CAPE group (MTX+CAPE treated), and control group. MTX was administered intraperitoneally (i.p.) with a single dose of 20 mg kg(-1) on the second day of experiment. CAPE was administered i.p. with a dose of 10 micromol kg(-1) day(-1) for 7 days. Malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and catalase (CAT) were determined in cerebellar tissue of rats. MTX caused to significant increase in MDA levels (an important marker of lipid peroxidation) in the MTX group compared with the controls (p = 0.006). CAPE significantly reduced the MTX induced lipid peroxidation in the MTX+CAPE group compared to the MTX (p = 0.007). The activities of SOD and CAT were significantly increased in the MTX group when compared with the control group (p = 0.0001, p = 0.004, respectively). The increased activities of these enzymes were significantly reduced by CAPE treatment (p = 0.004, p = 0.034, respectively). As a result, CAPE may protect from oxidative damage caused by MTX treatment in rat cerebellum.

The aim of this study was to investigate the possible effects of ellagic acid in brain and sciatic nerve tissues of diabetic rats. Also, the impact of ellagic acid on catalase and paraoxonase (PON-1) activities, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and nitric oxide (NO) were examined. The rats were randomly divided into four groups, with eight rats each: Normal controls (not diabetic), only ellagic acid treated (ellagic acid controls, not diabetic), Diabetic controls (streptozotocin, diabetic), ellagic acid-treated diabetic (streptozotocin + ellagic acid). After a 4 week experiment, rats were sacrificed, and biomarkers for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. There was significant depletion in the PON-1, catalase, and TAS levels in the brain and sciatic nerve tissues compared to the control groups (for both parameters, p<0.05). The values of catalase, PON-1 and TAS reversed back to normal levels in ellagic acid-treated diabetic rats compared to untreated diabetic rats (for both parameters, p<0.05). The levels of MDA, TOS, NO and, OSI in the brain and sciatic nerve tissues were higher in untreated diabetic rats compared to control group (for both parameters p<0.05). However, MDA, TOS, OSI, and NO levels were found to be significantly reduced in the ellagic acid-treated diabetic group compared to the untreated diabetic group in these tissues (for both parameters, p<0.05). In conclusion, the results of the present study suggested that ellagic acid exhibits neuroprotective effects against oxidative damage in diabetic rats.

The objective of the study was to assess the efficacy and tolerability of sodium valproate (VPA) on chronic daily headache (CDH) in a prospective, double-blind, randomized, placebo-controlled trial. Seventy patients were included in the study. Twenty-nine had chronic migraine (CM) and 41 had chronic tension-type headache (CTTH). VPA and placebo were applied for 3 months to 40 and 30 patients, respectively. Visual analog scale (VAS) and pain frequency (PF) were used for evaluation. VPA decreased the maximum pain VAS levels (MaxVAS) and PF at the end of the study (P = 0.028 and P = 0.000, respectively), but did not change general pain VAS (GnVAS) levels (P = 0.198). In CM patients, the decreases in MaxVAS, GnVAS and PF parameters were more in VPA treated patients (P = 0.006, P = 0.03, and P = 0.000, respectively). VPA treatment caused more reduction in PF than placebo in the CTTH subgroup (P = 0.000). VPA is effective in the prophylactic treatment of CDH by reducing MaxVAS levels and PF. It was more effective in CM than in CTTH.

The aim of this experimental study was to investigate the possible role of nitric oxide (NO) levels, and activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the pathogenesis of methotrexate-induced nephrotoxicity, and was the effect of caffeic acid phenethyl ester (CAPE), the potent free radical scavenger, in decreasing the toxicity. A total of 19 adult male rats were divided into three experimental groups, as follows: control group, MTX-treated group, and MTX+CAPE treated group. MTX were administered intraperitoneally (i.p.) with 20 mg/kg for single dose. CAPE was administered i.p. with a dose of 10 micromol//kg once daily for 7 days. The injection of MTX induced a significant increase in the activities of ADA and XO, and NO levels in renal tissue of rats (p < 0.0001). Co-treatment with CAPE caused a significantly decrease activities of ADA and XO, and the levels of NO in renal tissue (p < 0.0001). The results of this study revealed that NO, XO and ADA may play an important role in the pathogenesis of MTX-induced oxidative renal damage. CAPE may have protective potential in this process and it will become a promising drug in the prevention of this undesired side effect of MTX.

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