Protective role of phosphatidylcholine against cisplatin-induced renal toxicity and oxidative stress in rats

Although cisplatin is widely used in the treatment of cancers, clinical use of cisplatin is limited due to its nephrotoxicity. Pathophysiological mechanism of cisplatin-induced renal toxicity is a complex process and has not been fully understand. Reactive oxygen species (ROS) and oxidative stress have been presumed to be involved in this damage process. Phosphatidylcholine (PC) has antioxidant effect and prevents oxidative stress. Therefore, the present study aimed to investigate potential protective effects of PC on cisplatin-induced renal damage in rat. We examined the protective effects of PC on cisplatin-induced renal damage by assessment of serum creatinine, BUN, lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, superoxide dismutase activity and histophathological changes. PC ameliorated cisplatin-induced increases in serum creatinine, urea and oxidative stress. PC also decreased tubular degeneration and hypertrophy of glomeruli. PC may have a protective effect against cisplatin-induced nephrotoxicity in rats via enhancing antioxidant enzyme activity.     

The protective effects of astaxanthin against cisplatin-induced retinal toxicity

Purpose: This study investigated the toxic effects of an antineoplastic agent, cisplatin (CIS), on retinal cells and the potential capacity of astaxanthin (ASTA) to elicit a future therapeutic protocol in CIS-induced retinal toxicity.

Materials and methods: Six groups were formed for the assessment; control (healthy; Group 1), olive oil (olive oil only; Group 2), ASTA control group (ASTA only, Group 3), the single intraperitoneal (IP) dose of 16?mg/kg CIS (CIS only group; Group 4), 16?mg/kg CIS +25?mg/kg (IP) ASTA (Group 5), and 16?mg/kg CIS +75?mg/kg (IP) ASTA (Group 6). On the third day after CIS administration, rats in all groups were sacrificed under anesthesia and the analysis of the biochemical parameters and histopathological levels were performed.

Results: A significant decrease in GSH levels and increases in MDA, eNOS, and 8-OHdG expressions were recorded. Additionally, CIS treatment had caused acidophilic staining in retinal histological appearance. ASTA treatment reduced the increases in MDA, eNOS, and 8-OHdG levels following CIS administration and increased the levels of GSH expressions, as well.

Conclusions: These results may suggest that the ASTA molecule as a promising option to prevent retinal toxicity in patients receiving CIS treatment for malignant tumors.     

D-硝基精氨酸对小鼠肾损伤及氧化应激作用

目的研究D-硝基精氨酸(D-NNA)对小鼠的肾损伤及其氧化应激机制。方法 ICR小鼠ig给予D-NNA150,50和15 mg·kg-1,连续30 d。测定并计算肾系数;血液生化分析仪检测血清中肌酐(Crea)和尿素氮(BUN);分光光度法测定肾组织一氧化氮(NO),硫代巴比妥酸法测丙二醛(MDA)含量,比色法测定谷胱甘肽过氧化酶(GSH-Px)和超氧化物歧化酶(SOD)活性;观察肾病理组织学变化。结果与5%葡萄糖对照组相比,D-NNA 150,50和15 mg·kg-1组血清中BUN分别明显升高了83.6%,36.2%和27.4%(P<0.05),D-NNA150和50 mg·kg-1组血清中Crea分别明显升高了281.6%和10.6%(P<0.05);D-NNA150 mg·kg-1组肾系数和NO水平分别明显降低了5.6%和25.5%(P<0.05);D-NNA150和50 mg·kg-1组肾组织中MDA水平分别明显升高了69.0%和36.9%(P<0.01),SOD活性和GSH-Px活性分别明显下降了17.4%和17.7%,7.3%和13.7%(P<0.05);D-NNA150 mg·kg-1组病理检查可见肾小管损伤,嗜碱性变,萎缩或囊性扩张和间质炎性浸润,D-NNA50和15 mg·kg-1组出现炎症细胞浸润。结论 D-NNA对小鼠肾有一定的损伤作用,其作用机制可能与D-NNA的手性转化产物L-NNA导致NO合成减少,产生ROS有关。     

Effect of oleuropein against chemotherapy drug-induced histological changes,oxidative stress,and DNA damages in rat kidney injury

Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection. After exposure to the chemotherapy agent and OLE, oxidative DNA damage was quantitated in the renal tissue of experimental animals by measuring the amount of 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts. Malondialdehyde (MDA) level, total oxidative stress (TOS), and total antioxidant status (TAS) were assessed to determine the oxidative injury in kidney cells. The histology of the kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), Masson trichrome, and amyloid. In addition, the blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE) levels were established. Our experimental data showed that tissue 8-OHdG levels were significantly higher in the cisplatin group when compared to the control group. The glomerular cells were sensitive to cisplatin as tubular cells. In addition, treatment with cisplatin elevated the levels of BUN, UA, CRE, and TOS, but lowered the level of TAS compared to the control group. The OLE therapy modulated oxidative stress in order to restore normal kidney function and reduced the formation of 8-OHdG induced by cisplatin. Furthermore, the OLE treatment significantly reduced pathological findings in renal tissue. We demonstrate for the first time that OLE presents significant cytoprotective properties against cisplatin-induced genotoxicity by restoring the antioxidant system of the renal tissue. According to our findings, OLE is a promising novel natural source for the prevention of serious kidney damage in current chemotherapies.     

Crocin attenuates cisplatin-induced renal oxidative stress in rats

Reactive oxygen species (ROS) and oxidative damage are the most important factors in cisplatin-induced acute renal failure. This study examined the protective effects of crocin against cisplatin-induced renal oxidative stress in rat. Animals were divided into five groups (n = 6). Group 1 received normal saline (2 ml/day, i.p.). Group 2 received a single dose of cisplatin (5 mg/kg, i.p.). Groups 3–5 received crocin (100, 200, and 400 mg/kg, i.p., respectively) for four consecutive days beginning 1-h before a single dose of cisplatin (5 mg/kg) on day 1. On day 5, blood samples were drawn and kidneys were removed for histopathological, biochemical and RT-PCR examinations. Twenty four hours urinary chemistries were measured. Blood urea and creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower compared to the cisplatin-treated group. Histopathological studies showed massive damage in the S₃ segment of proximal tubules in cisplatin-treated group but not in crocin-treated groups. Crocin treatment resulted in a significant reduction in malondialdehyde (MDA) concentration and produced a significant elevation in total thiol and glutathione peroxidase concentrations. There was a significant elevation in the mRNA expression of glutathione peroxidase in crocin-treated groups. The results suggest that crocin attenuates cisplatin-induced renal oxidative stress in rats.     

Protective effects of emodin against cisplatin‐induced oxidative stress in cultured human kidney (HEK 293) cells

Emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions, and recent studies indicated that it reduces cellular oxidative stress induced by various insults and drugs. Cisplatin is an anticancer drug that is associated with nephrotoxicity and induces oxidative stress in cultured human kidney (HEK 293) cells. This study aimed to assess the in‐vitro antioxidant properties of the emodin against cisplatin‐induced oxidative stress in HEK 293 cells. Our study revealed that emodin acted as a potent free radical scavenger and provided nephroprotection against cisplatin‐induced oxidative stress. Emodin as low as 0.5 µm did not decrease cell viability and restored the cisplatin‐induced glutathione depletion and total antioxidant capacity in a dose‐dependent manner. Emodin augmented the cisplatin‐induced inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S‐transferase, glutathione reductase and superoxide dismutase). These results suggest that emodin has the potential to be used as an adjunct therapeutic agent in patients receiving cisplatin treatment. Copyright © 2012 John Wiley & Sons, Ltd.     

Contribution of oxidative stress to TiO2 nanoparticle-induced toxicity

With the rapid development of nanotechnology, titanium dioxide nanoparticles (TNPs) are widely used in many fields. People in such workplaces or researchers in laboratories are at a higher risk of being exposed to TNPs, so are the consumers. Moreover, increasing evidence revealed that the concentrations of TNPs are elevated in animal organs after systematic exposure and such accumulated TNPs could induce organ dysfunction. Although cellular responses such as oxidative stress, inflammatory response, apoptosis, autophagy, signaling pathways, and genotoxic effects contribute to the toxicity of TNPs, the interrelationship among them remains obscure. Given the pivotal role of oxidative stress, we summarized relevant articles covering the involvement of oxidative stress in TNPs’ toxicity and found that TNP-induced oxidative stress might play a central role in toxic mechanisms. However, available data are far from being conclusive and more investigations should be performed to further confirm whether the toxicity of TNPs might be attributed in part to the cascades of oxidative stress. Tackling this uncertain issue may help us to comprehensively understand the interrelationship among toxic cellular responses induced by TNPs and might shed some light on methods to alleviate toxicity of TNPs.     

Nephroprotective activity of Macrothelypteris oligophlebia rhizomes ethanol extract

Context: Macrothelypteris oligophlebia (Bak.) Ching (Thelypteridaceae) is a Chinese herbal medicine used traditionally for the treatment of diseases such as edema, boils, burns, and roundworms. However, research about the nephroprotective potential of this plant is not available.

Objective: Present study was designed to evaluate the protective effect of ethanol extract of M. oligophlebia rhizomes (EMO) on gentamicin (GM)-induced nephrotoxicity.

Materials and methods: Rats were intraperitoneal (i.p.) injected with GM (100?mg/kg) to induce nephrotoxicity and simultaneously EMO (250 and 500?mg/kg) was orally given to GM-treated rats for 8 days. Blood urea nitrogen (BUN), serum creatinine (Cr), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were evaluated in renal tissues. Histopathological analysis was used for evaluation of the renal damage.

Results: Administration with GM-induced renal dysfunction in rats. Pre-treatment with EMO (500?mg/kg) significantly decreased the levels of BUN, Cr, MDA and NO (decreased BUN from 12.71?±?1.28 to 7.19?±?0.23 mmol/l, Cr from 39.77?±?5.34 to 19.17?±?0.90 μmol/l, MDA from 5.60?±?0.37 to 2.63?±?0.24 nmol/ml, and NO from 868.17?±?22.67 to 589.51?±?8.83 μmol/ml), and also restored the activities of renal antioxidant enzymes (SOD, CAT, and GSH-Px) (restored SOD from 1.59?±?0.17 to 2.94?±?0.13?U/mg protein, CAT from 3.22?±?0.34 to 10.57?±?0.27?U/mg protein, and GSH-Px from 9.11?±?1.29 to 20.72?±?1.83?U/mg protein).

Discussion and conclusion: Our results suggest that the rhizomes of M. oligophlebia potentially have a protective role in renal tissue against oxidative stress in acute renal failure.     

Effects of Pycnogenol on cisplatin-induced optic nerve injury: an experimental study

Aim: To determine the effects of Pycnogenol on cisplatin-induced optic nerve damage.

Material and method: Totally 18 albino Wistar male rats were assigned into three groups, with six rats in each group as follows: healthy controls (HC group), only cisplatin (2.5?mg/kg) administered group (CIS group) and Pycnogenol (40?mg/kg)?+?cisplatin (2.5?mg/kg) administered group (PYC group). We analyzed the levels of malondialdehyde (MDA) as a marker of lipid peroxidation and oxidative stress, total glutathione (tGSH) as a marker of antioxidant status, nuclear factor-kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) as inflammatory markers, total oxidative status (TOS) and total antioxidant status (TAS) on eye tissue together with histopathological evaluation of optic nerve in an experimental model.

Results: In CIS group MDA, TOS, TNF-α and NF-κB levels were statistically significantly higher (p?p?p?p?Conclusion: Pycnogenol pretreatment was highly effective in preventing augmentation of cisplatin-induced oxidative stress and inflammation in eye tissue.     

Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in wistar rats

5-Fluorouracil (5-FU) is a potent antineoplastic agent commonly used for the treatment of various malignancies. It has diverse adverse effects such as cardiotoxicity, nephrotoxicity and hepatotoxicity which restrict its wide and extensive clinical usage. It causes marked organ toxicity coupled with increased oxidative stress and apoptosis. Chrysin (CH), a natural flavonoid found in many plant extracts, propolis, blue passion flower. It has antioxidative and anti-cancerous properties. The present study was designed to investigate the protective effects of CH against 5-FU induced renal toxicity in wistar rats using biochemical, histopathological and immunohistochemical approaches.Rats were subjected to prophylactic oral treatment of CH (50 and 100 mg/kg b.wt.) for 21 days against renal toxicity induced by single intraperitoneal administration of 5-FU (150 mg/kg b.wt.). The possible mechanism of 5-FU induced renal toxicity is the induction of oxidative stress; activation of apoptotic pathway by upregulation of p53, bax, caspase-3 and down regulating Bcl-2. However prophylactic treatment of CH decreased serum toxicity markers, increased anti-oxidant armory as well as regulated apoptosis in kidney. Histopathological changes further confirmed the biochemical and immunohistochemical results. Therefore, results of the present finding suggest that CH may be a useful modulator in mitigating 5-FU induced renal toxicity.     

Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice

Rosmarinic acid (RA) is a natural phenolic compound with a broad range of applications, from food preservatives to cosmetics. Increasing amounts of evidence suggests its beneficial effects against various pathological conditions. The aim of this study was to investigate the therapeutic activity of rosmarinic acid (RA) against cisplatin (CP)-induced nephrotoxicity. RA was administered by oral gavage at doses of 1, 2 and 5 mg/kg for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Twenty four hours later, mice were sacrificed. Treatment with RA significantly ameliorated histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP. Oxidative stress induced by CP, evidenced by increased renal 4-hydroxynonenal (4-HNE), cytochrome P450 2E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced by RA administration. Moreover, RA inhibited the expression of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-α (TNF-α), indicating the inhibition of inflammation. Additionally, RA exhibited antiapoptotic activity through the reduction of p53, phosphorylated p53 and active caspase-3 expression in the kidneys. These findings show that RA ameliorates CP-induced oxidative stress, inflammation and apoptosis in the kidneys. The nephroprotective activity of RA could be, at least in part, attributed to reduced CYP2E1 expression.     

Amelioration of cisplatin-induced nephrotoxicity by extracts of Hemidesmus indicus and Acorus calamus

Administration of commonly used anticancer drug cisplatin [cis-diamminedichloroplatinum (II)] at pharmacologically relevant concentrations (12?mg/kg body weight) resulted in severe renal toxicity as evidenced from histopathological observations and biochemical alterations in the renal tissue. The extracts of medicinal plants Hemidesmus indicus L. (Apocynaceae) and Acorus calamus L. (Araceae) protected the renal tissue effectively from cisplatin-induced toxicity. Treatment of cisplatin-administered animals with the plant extracts could prevent the drug-induced oxidative damage in the renal tissue as evidenced from the decreased levels of lipid peroxidation and enhanced activities of the antioxidants in the renal tissue. Cisplatin treatment increased serum urea level to 41.3?±?2.86?mg/dL and administration of the extracts of H. indicus and A. calamus brought down the level to 34.54?±?0.37 and 30.12?±?0.95?mg/dL, respectively. Serum creatinine levels were increased to 1.1?±?0.02?mg/dL following cisplatin administration, and treatment with extracts of H. indicus and A. calamus brought this down to 0.76?±?0.09 and 0.61?±?0.06?mg/dL, respectively. The histopathological observations indicated that treatment with the H. indicus and A. calamus extracts restored the cisplatin-induced structural alterations in the renal tissue.     

Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: probable role of p38MAPK and p53

Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage.     

Nephroprotective potential of Bacopa monniera on hypercholesterolemia induced nephropathy via the NO signaling pathway

Context: Bacopa monniera L. (Scrophulariaceae) is used as a traditional medicine in India for various ailments such as epilepsy, mental disorders, and also as a cardio-tonic. However, its nephroprotective role is still unknown.

Objective: The present study assesses the modulatory impact of the alcoholic (ethanol) extract of Bacopa monniera (AEBM) on renal oxido-lipidemic stress in hypercholesterolemic rats.

Materials and methods: B. monniera (1?kg) was extracted with 90% ethanol, filtered, and dried (52?g). Group-I rats as control, Group-II rats fed with a hypercholesterolemic diet (HCD) for 45?d [4% cholesterol and 1% cholic acid], Group-III rats fed with HCD for 45?d?+?AEBM (40?mg/kg, body weight) for last 30?d, and Group-IV AEBM alone rats. Blood and kidney were removed to analyze lipid, antioxidant status, and histological analysis.

Result: The levels of total cholesterol (TC), triacylglycerol (TG), phospholipids (PLs), renal functional parameters (urea, creatinine, and uric acid), and lipid peroxidation (LPO) products were significantly attenuated (p?S-transferase (GST), and glutathione reductase (GR)) and non-enzymic antioxidant (GSH, Vit-C, and Vit-E) were significantly increased (p?p?Discussion and conclusion: From this study, we hypothesized that AEBM can act as renoprotective agent by attenuating the renal oxido-lipidemic stress via regulating NOS level and thereby protects the nephron in hypercholesterolemic rats.     

葛根素在减轻创伤性脑损伤氧化应激反应中的作用

目的：探究葛根素是否能有效减轻创伤性脑损伤（TBI）中的氧化应激反应。方法选择成年雄性 SD大鼠60只构建 TBI 模型并随机平分为模型组,假手术组及葛根素给药组（给药组）,每组20只。检测3组大鼠在不同时间点氧化应激相关指标[超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH－Px）、过氧化氢酶（CAT）、丙二醛（MDA）]活性及含量变化。结果氧化应激相关指标检测中,给药组与模型组比较,其中第3、7天 SOD、CAT 活性以及 MDA、NO 含量与同时间点模型组比较差异有统计学意义（ P ＜0．05）。用药组与模型组比较,均能不同程度升高GSH 含量及 GSH－Px 活性（ P ＜0．05）,其中给药组第3天及第7天 GSH 含量及 GSH－Px 活性较同时间点模型组比较差异有统计学意义（ P ＜0．05）。结论根据对不同氧化应激指标检测所得结果可以看出葛根素可有效减轻创伤性脑损伤所带来的氧化应激损伤。     

Intraperitoneal glycerol induces oxidative stress in rat kidney

1. Glycerol has been used for the treatment of intracranial hypertension, cerebral oedema and glaucoma. Experimentally, intramuscular administration of hypertonic glycerol solution is used to produce acute renal failure. In this model, glycerol causes rhabdomyolysis and myoglobinuria, resulting in the development of renal injury. The pathogenesis is thought to involve vascular congestion, the formation of casts and oxidative stress. However, the effect of glycerol itself independent of rhabdomyolysis has not been investigated. Therefore, the aim of the present study was to investigate the effects of i.p. glycerol on some biochemical and oxidative stress parameters in the kidney of young rats. 2. Rats received 10 mL/kg, i.p., hypertonic glycerol solution (50% v/v) or saline (NaCl 0.85 g%) followed by 24 h water deprivation. Twenty-four hours after the administration of glycerol, rats were killed. Creatinine levels and the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined in the plasma. In addition, CK, pyruvate kinase and LDH activity and oxidative stress parameters (free radical formation, lipid peroxidation and protein carbonylation) were measured in renal tissue. 3. Glycerol did not alter plasma CK activity and increased plasma creatinine levels, suggesting renal insufficiency and the absence of rhabdomyolysis. Renal CK and pyruvate kinase activity was decreased, suggesting diminution of energy homeostasis in the kidney. Plasma and renal LDH activity was decreased, whereas the formation of free radicals, lipid peroxidation and protein carbonylation were increased, suggesting oxidative stress. 4. These results are similar to those described after the intramuscular administration of glycerol. Therefore, it is possible that glycerol may provoke renal lesions by mechanisms other than those induced by rhabdomyolysis.     

Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity

Kallikrein-kinin system (KKS) is involved in vascular reactivity and inflammatory response to cytotoxic drugs. Since cisplatin is a widely used chemotherapy and its cytotoxic mechanism can trigger inflammation and oxidative damage, in this work we evaluated the role of KKS in an animal model of cisplatin-induced ovarian toxicity. Biomarkers of ovarian stem cells, activity of KKS, inflammation and oxidative damage were measured in ovarian tissue of C57BL/6 female mice treated with vehicle or cisplatin (2.5 mg/kg). Cisplatin group presented greater number of atretic follicles, and lower numbers of antral and total viable follicles. Ki67, DDX4 and OCT-4 markers were similar between groups. Cisplatin triggered plasma and ovarian tissue kallikrein generation; and increased expression of bradykinin receptors B1 and B2. Neutrophil and macrophage infiltration markers increased. Superoxide anion generation also increased, while reduced glutathione levels decreased. These results suggest that KKS is activated and contributes to ovarian injury during cisplatin treatment.     

Nephroprotective effect of cilostazol and verapamil against thioacetamide-induced toxicity in rats may involve Nrf2/HO-1/NQO-1 signaling pathway

Cilostazol and verapamil are widely used cardiovascular drugs, explored a beneficial effect on different organs-induced toxicities. We investigated whether the Nrf2 (nuclear erythroid factor 2) and its downstream pathway are involved in the protective role of these drugs against TAA-induced renal damage. Renal biomarkers (creatinine and urea) and histopathology were observed. Antioxidant and oxidant indicators; superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA) and total nitrite (NO) were also measured. Antioxidant markers like; Nrf2/hemoxegenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions were determined by ELISA and immunohistochemistry. Cilostazol and verapamil pretreatment improved serum creatinine and urea elevation. Examined drugs also have an ameliorative effect on TAA-induced elevation in MDA and NO activities and antioxidant enzymes; SOD and GSH. Additionally, the pretreated drugs significantly up-regulated Nrf2/HO-1/NQO-1 expression levels. In conclusion, cilostazol and verapamil exerted their protective effects partially via a Nrf2/HO-1/NQO-1 activation pathway with anti-oxidant roles.     

Acrylonitrile induced apoptosis via oxidative stress in neuroblastoma SH-SY5Y cell

Acrylonitrile (ACN) is a chemical that is widely used in the production of plastics, acrylic fibers, synthetic rubbers and resins. It has been reported that ACN can cause oxidative stress, a condition which is well recognized as an apoptotic initiator; however, information regarding ACN-induced apoptosis is limited. This present study investigated whether ACN induces apoptosis in human neuroblastoma SH-SY5Y cells, and whether its apoptotic induction involves oxidative stress. The results showed that ACN caused activation of caspase-3, a key enzyme involved in apoptosis, in a dose- and time-dependent manner. Detection of sub-G1 apoptotic cell death and apoptotic nuclear condensation revealed that ACN caused an increase in the number of apoptotic cells indicating ACN induces apoptosis in SH-SY5Y cells. ACN dose- and time-dependently increased the level of proapoptotic protein, Bax. Pretreatment with N-acetylcysteine (NAC), an antioxidant, attenuated caspase-3 activation by ACN, as evidenced by a reduction in proteolysis of PARP, a known caspase-3 substrate, as well as in the number of sub-G1 apoptotic cells. Moreover, induction of Bax by ACN was abolished by NAC. Taken together, the results indicate that ACN induces apoptosis in SH-SY5Y cells via a mechanism involving generation of oxidative stress-mediated Bax induction.