Xuezhikang ameliorates contrast media-induced nephropathy in rats via suppression of oxidative stress,inflammatory responses and apoptosis

Background: The aim of this study was to assess the preventive effect of xuezhikang (XZK) to replace atorvastatin on the contrast media-induced acute kidney injury (CI-AKI).

Methods: The male Sprague–Dawley rats were divided into five groups: group 1 (sham), injected with normal saline; group 2 (XZK), treated with XZK; group 3 contrast media (CM), injected with CM; group 4 (CM?+?ATO), injected with CM?+?pretreatment with atorvastatin; group 5 (CM?+?XZK), injected with CM?+?pretreatment with XZK. Twenty-four hours after injection with normal saline or CM, the blood sample and the kidneys were collected for the measurement of biochemical parameters, oxidative stress markers, nitric oxide production, inflammatory parameters, as well as renal histopathology and apoptosis detection.

Results: Our results indicated that XZK restored the renal function by reducing serum blood urea nitrogen (BUN) and serum creatinine (Scr), depressing renal malondialdehyde (MDA), increasing renal NO production, decreasing TNF-ɑ and IL-6 expression, attenuating renal pathological changes and inhibiting the apoptosis of renal tubular cells.

Conclusion: XZK’s therapeutic effect is similar, or even better than atorvastatin at the same effectual dose in some parts.     

Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion

Aim: MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model.

Methods: We used 12–16 weeks-old Wistar-Albino rats that weigh 300–350?g. Rats (n, 6) were randomized into four groups (Control, IR, IR?+?CAP, IR?+?TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed.

Results: Urea, creatinine, TOS, OSI levels of IR?+?CAP, and IR?+?TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR?+?TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR?+?CAP and IR?+?TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR?+?CAP and IR?+?T groups than IR group.

Conclusion: We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.     

N-acetylcysteine protects against star fruit-induced acute kidney injury

Background: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect.

Materials and methods: Male Wistar rats received SF juice (4?mL/100?g body weight) by gavage after a 12?h fasting and water deprivation. Fasting and water deprivation continued for 6?h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n?=?6): received tap water; SF?+?NAC (n?=?6): received NAC (4.8?g/L) in drinking water for 48?h after gavage; and Sham (n?=?6): no interventions. After 48?h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments.

Results: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy.

Conclusions: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.     

Evaluation of plasma oxidative stress,with or without antioxidant supplementation,in superficial partial thickness burn patients: a pilot study

Background: Oxidative stress is one of the main causes of pathophysiological alterations observed during burn injury. The present pilot study aimed to determine whether a specific oral antioxidant supplementation could in any way influence free radical blood values in patients affected by superficial partial thickness burns.

Materials and methods: Plasma oxidants and plasma antioxidant capacity were analysed in 20 superficial partial thickness burn patients for a 2-week period; patients were randomly divided into two groups, one of which was supported with a specifically designed oral antioxidant formula (Squalene 100?mg, Vitamin C 30?mg, Coenzyme Q10 10?mg, Zinc 5?mg, Beta Carotene 3.6?mg, Bioflavonoids 30?mg, Selenium 55?mcg) administered daily, starting from the day of admission, for the whole study period.

Results: No significant differences were found in plasma oxidants and plasma antioxidant capacity between the two groups of patients.

Conclusions: These results did not reflect any significant benefits of an antioxidant oral supplementation at usual dosages when considering oxidative plasmatic values of superficial partial thickness burn patients.     

Protective effects of gallic acid against methotrexate-induced toxicity in rats

Background: Methotrexate, as a chemotherapy drug, can cause chronic liver damage and oxidative stress. Aim of this study was to evaluate the preventive effect of gallic acid (GA) on methotrexate (MTX)-induced oxidative stress in rat liver.

Methods: Twenty-eight male rats were randomly divided into four groups as control, MTX (20?mg/kg, i.p.), MTX?+?GA (30?mg/kg/day, orally) and GA treated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. Malondialdehyde (MDA) and glutathione (GSH) levels and hepatic antioxidant enzymes activities including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed in liver tissue. The expression of SOD2 and GPx1 genes were evaluated by real-time RT-PCR and liver histopathology was evaluated by light microscopy.

Results: The result obtained from current study showed that GA remarkably reduced MTX-induced elevation of AST, ALT and ALP and increased MTX-induced reduction in GSH content, GPx, CAT and SOD activity as well as GPx1 and SOD2 gene expressions. Histological results showed that MTX led to liver damage and GA could improve histological changes.

Conclusions: Our results indicate that GA ameliorates biochemical and oxidative stress parameters in the liver of rats exposed to MTX.     

Iron restriction prevents diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rat

Abstract

High body iron levels are found in type 2 diabetes mellitus (DM). Iron excess leads to tissue injury through free radical formation. We investigated the effect of iron restriction on renal damage in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2?DM. OLETF rats (n?=?18) were divided into three groups at 10 weeks of age: high fat diet containing 8% NaCl (HFS, n?=?6), HFS diet with iron restricted (HFS?+?IR, n?=?6), and HFS with hydralazine (HFS?+?Hyd, n?=?6). Long-Evans Tokushima (LETO) rats served as control. Iron restriction decreased hemoglobin levels, systolic blood pressure, and urinary excretion of protein and 8-hydroxy-2'-deoxyguanosine in the OLETF rats fed with HFS diet. Compared to the HFS group, the expression of desmin, renal glomerular injury marker and iron deposition in the renal tubules were attenuated in the HFS?+?IR group but not in the HFS?+?Hyd group at 26 weeks of age. Moreover, renal hypoxia (evaluated as pimonidazole adducts) was improved in the HFS?+?IR group compared to the HFS group in spite of anemia. Iron restriction prevented the production of reactive oxygen species and the development of early stage nephropathy in OLETF rats. Iron restriction may be beneficial in prevention of nephropathy in type 2?DM.     

Association between GSTM1, GSTT1, and GSTP1 variants and the risk of end stage renal disease

Introduction: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD.

Materials and methods: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC).

Results: We found that GSTM1 and GSTT1 null genotypes (GSTT1?/GSTM1?) increased the risk of ESRD by 1.8 times (p?<?0.001) and the increased risk of ESRD for GSTM-null (T1+-M1?) genotype was 3.04 times (p?=?0.002). ESRD patients carriers the GST (GSTM1-null?+?GSTT1-null?+?GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p?<?0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA.

Conclusion: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.     

Medical ozone therapy reduces shock wave therapy-induced renal injury

Objectives: Extracorporeal shock wave (ESW) lithotripsy is the preferred treatment modality for uncomplicated kidney stones. More recently free oxygen radical production following ESW application has been considered to be crucial in shock wave-induced renal damage. It has been shown that ozone therapy (OT) has ameliorative and preventive effects against various pathological conditions due to increased nitro-oxidative stress. In current study, we aimed to evaluate the efficacy of OT against ESW-induced renal injury. Methods: Twenty-four male Sprague–Dawley rats were divided into three groups: sham-operated, ESW, and ESW?+?OT groups. All groups except sham-operated group were subjected to ESW procedure. ESW?+?OT group received 1?mg/kg/day of oxygen/ozone mixture intraperitoneally at 2?h before ESW, and OT was continued once a day for consecutive three days. The animals were killed at the 4th day, and kidney tissue and blood samples were harvested for biochemical and histopathologic analysis. Results: Serum ALT and AST levels, serum neopterin, tissue nitrite/nitrate levels, and tissue oxidative stress parameters were increased in the ESW group and almost came close to control values in the treatment group (p?p?p?p?Conclusion: OT ameliorates nitro-oxidative stress and reduces the severity of pathological changes in the experimental ESW-induced renal injury of rat model.     

LPS ameliorates renal ischemia/reperfusion injury via Hsp27 up-regulation

Purpose

We have recently reported lipopolysaccharide (LPS) pretreatment attenuated renal ischemia/reperfusion injury (IRI), but the exact mechanism remains to be well elucidated. It was reported that heat shock protein (Hsp) 27 was up-regulated after administration of LPS, but whether a direct link existed between Hsp27 up-regulation and LPS-induced protection against renal IRI is still unknown.

Methods

Mice were exposed to IRI or sham procedure, with pretreatment of LPS or not. Quercetin, an inhibitor of Hsp27 synthesis, was used, and an RNA interference with adenovirus vector using short hairpin RNA targeting Hsp27 was developed for inhibition of Hsp27 in mice. In addition, mice trans-infected with adenovirus vector encoding Hsp27 were used to testify the role of Hsp27 overexpression in LPS-induced renoprotection. Renal function, histological damage, inflammatory reaction, oxidative stress and apoptosis indices were measured. Western blot analysis was used to detect expression of Hsp27.

Results

We found LPS pretreatment stimulated renal up-regulation of Hsp27 and reduced renal IRI proven by less renal dysfunction, histological damage, inflammatory reaction, oxidative stress and apoptosis. It was observed that inhibition of Hsp27 synthesis by Quercetin abolished LPS-induced renoprotective effects. After renal knockdown of Hsp27, LPS-induced tolerance against renal IRI was largely removed. Mice with Hsp27 overexpression showed significantly improved renal function after IRI and LPS combined with Hsp27 overexpression had a synergistic effect on protection against renal IRI.

Conclusion

Administration of LPS produces protective effects against renal IRI via Hsp27 up-regulation. Preconditional Hsp27 up-regulation might have a great potential for the treatment of renal IRI via ameliorating apoptosis.

     

Recombinant Human Erythropoietin Restrains Oxidative Stress in Streptozotocin-induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

BackgroundRenal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes mellitus (DM) in surgical practice. Oxidative stress plays a crucial role in this process. Recombinant human erythropoietin (rhEPO) is usually used to treat anemia resulting from several diseases. However, the functional involvement of rhEPO in diabetic RI/RI remains unclear. The present study was intended to investigate the antioxidant role of rhEPO on RI/RI in DM rats.MethodsThe bilateral renal arteries and veins of streptozotocin-induced diabetic rats were subjected to 45 minutes of ischemia followed by 1, 6, and 24 hours of reperfusion with or without rhEPO pretreatment at the beginning of an I/R procedure. The renal tissue pathomorphology, renal function, oxidative stress, and inflammatory response were evaluated by detection of a series of indices by hematoxylin-eosin staining, commercial kits, enzyme-linked immunosorbent assay, and spectrophotofluorometry, respectively.ResultsCompared to the I/R group, renal function was significantly advanced in the erythropoietin group, whose subjects were also subjected to renal tissue injury, oxidative stress, and inflammation.ConclusionThese results suggest that rhEPO preconditioning can attenuate diabetic RI/RI through regulating endogenous antioxidant activity.     

Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C

Background: The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity.

Materials and methods: Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5?mg/kg intraperitoneally); (3) Agmatine (AGM; 10?mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP?+?AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation.

Results: In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone.

Conclusions: Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.     

Exogenously administered adenosine attenuates renal damage in streptozotocin-induced diabetic rats

Background: Diabetic nephropathy (DNP) is one of the most serious complications of diabetes mellitus (DM). In the present study, we investigated the potential of adenosine as a therapeutic candidate for preventing DNP.

Methods: Twenty-one adult male rats were included in the study. Fourteen rats were administered a single dose of 60?mg/kg streptozotocin (STZ) to induce diabetes. Seven rats served as normal control group. Diabetic rats were randomly divided into two groups: one group was treated with 1?mL/kg saline/day (DM?+?saline) and the other group was treated with 5?mg/kg/day adenosine (DM?+?adenosine) for 6?weeks. After 6?weeks, biochemical parameters including urea, creatinine, blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and tumor necrosis factor-α (TNF-α) were measured in plasma samples. Also, kidneys were removed for histopathological assessment.

Results: Both of plasma KIM-1 and TNF-α levels were significantly higher in DM?+?saline group compared to controls. However, treatment of diabetic rats with adenosine significantly decreased the plasma KIM-1 and TNF-α levels compared to DM?+?saline group. Significant histopathological changes were observed in diabetic rats whereas adenosine treatment effectively prevented these changes.

Conclusions: The findings of the present study suggest that adenosine may be a useful therapeutic agent for preventing DNP.     

Glycogen Synthase Kinase-3β Inhibitor Attenuates Renal Damage Through Regulating Antioxidant and Anti-inflammation in Rat Kidney Transplant With Cold Ischemia Reperfusion

BackgroudThe glycogen synthase kinase-3β inhibitor thiadiazolidinone derivative 8 (TDZD-8) has been reported to reduce renal ischemia reperfusion (I/R) injury through inhibiting cell damage. However, it is not known whether TDZD-8 could also play a role in protecting the kidney in rat kidney transplantation with renal cold I/R. The aim of the present study was to explore the possible role of TDZD-8 in protecting renal damage in a cold I/R model of rat kidney transplantation.MethodsThe rat model of kidney transplantation with renal cold I/R was established. The renal tissue pathomorphologic changes, renal function, oxidative stress, and inflammatory response were evaluated by detection of a series of indices by hematoxylin and eosin staining, commercial kits, enzyme-linked immunosorbent assay, and spectrophotofluorometry, respectively.ResultsCompared with I/R and Graft groups, renal function was significantly improved in TDZD and TDZD-G groups, which were accompanied by the reduction of renal injury, oxidative stress, and inflammation.ConclusionsThese results suggest that preconditioning with glycogen synthase kinase-3β inhibitor can attenuate kidney transplantation with renal cold I/R through regulating endogenous antioxidant activity and inflammation.     

The usefulness of carvedilol and nebivolol in preventing contrast nephropathy in rats

Abstract

Background: Oxidative stress and vasoconstriction appear to be important components of contrast nephropathy (CN) pathogenesis, and both carvedilol and nebivolol are known to have vasodilatory and antioxidant effects. Aims: This study aimed to investigate whether carvedilol and nebivolol play preventive roles against developing CN and to compare the effects of each. Materials and methods: Wistar albino rats were divided into control (C, n?=?6), contrast material (CM, n?=?6), carvedilol (CV, n?=?7), carvedilol?+?contrast material (CV?+?CM, n?=?7), nebivolol (N, n?=?7), and nebivolol?+?contrast (N?+?CM, n?=?7) groups. Following 3 days of dehydration, 6?mL/kg diatrizoate was administered to each rat. Carvedilol was given at a dose of 2?mg/kg and nebivolol at a dose of 1?mg/kg by way of oral gavage. After scarification, total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were studied in renal tissue. Histopathological findings were graded as mild (+), moderate (++), and severe (+++). Results and discussion: Most of the histopathological findings and MDA levels were significantly higher in the CM group than that in the C, CVCM, and NVCM groups, whereas there was no significant difference between the C, CVCM and NVCM groups. TAC level in the CM group was significantly lower than in all other groups. There was no difference in SOD among groups. Conclusions: Carvedilol and nebivolol both prevent development of nephropathy related to CMs by decreasing oxidative stress. Neither is superior to the other.     

18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants

Objectives: 18β-glycyrrhetinic acid (18β-GA) has multiple beneficial and therapeutic effects. However, its protective roles on methotrexate (MTX)-induced renal injury are not well defined. In the present study, we investigated the possible protective effects of 18β-GA against MTX-induced nephrotoxicity in rats.

Materials: 18β-GA (50 and 100?mg/kg) was administered for 7 days either before or after MTX. The rats were decapitated and kidney and serum samples were collected.

Results: MTX-induced renal injury in rats was evidenced by the significant (p?p?p?p?Conclusions: These results indicate that 18β-GA has a protective effect on MTX-induced nephrotoxicity with possible mechanisms of attenuating oxidative stress and inflammation through up-regulating the Nrf2/ARE signaling. These findings make 18β-GA candidate as a potent agent in preventing MTX-induced kidney injury.     

N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via activation of SOD2, eNOS,and MMP3 protein expressions

Objective: To investigate the molecular mechanisms of colistimethate sodium-induced nephrotoxicity and the protective effect of N-acetylcysteine (NAC) against nephrotoxicity.

Methods: Twenty-eight Wistar rats were divided into four groups comprised of control, colistin, NAC, and colistin–NAC co-treatment, respectively. Serum creatinine and urine N-acetyl-β-d-glucosaminidase (NAG) levels were measured at different time intervals. Histological changes, apoptosis, total oxidant and antioxidant status, and the expression levels of endothelial nitric oxide synthase (eNOS), superoxide dismutase 2 (SOD2), and matrix metalloproteinase 3 (MMP3) were evaluated in renal tissue.

Results: In the colistin group, post-treatment creatinine levels were higher than pretreatment levels (p?=?.001). There was a significant increase in urine NAG level following colistin treatment on day 10, compared to the baseline value and the first day of treatment (p?=?.001 and .0001, respectively). Urine NAG levels were higher in the colistin group on the 10th day of treatment than in the other groups (p?Conclusions: N-acetylcysteine prevented colistin-induced nephrotoxicity through activation of expression levels of SOD2, eNOS, and MMP3.     

Treatment with troxerutin protects against cisplatin-induced kidney injury in mice

Background: Cisplatin (CP) is a synthetic and anticancer drug, and one of the major side effects of CP is nephrotoxicity. This study was done to evaluate the renoprotective effects of troxerutin (Tro) in nephrotoxicity induced by CP in male mice.

Methods: In this experimental study, 28 male mice were divided randomly into four groups. Mice were treated with CP (20?mg/kg, i.p.) then Tro (75 and 150?mg/kg/day, po) was administered for three consecutive days. Blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidney tissues were used for histological examination and biochemical assays. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were assessed in renal tissue.

Results: Results showed a significant increase in the Cr, BUN and MDA levels and a significant decrease in the renal SOD and GPx activity by CP administration. Treatment with Tro for three consecutive days attenuated these changes. Also, the renoprotective effect of the Tro was confirmed by the histological examination of the kidneys.

Conclusions: Our results demonstrated that Tro has protective effects against CP-induced nephrotoxicity through improving the biochemical indices and the oxidative stress parameters.     

Quercetin ameliorates methotrexate-induced renal damage,apoptosis and oxidative stress in rats

Abstract

Background: In the present study, the protective and therapeutic effects of quercetin (QE) on renal injury induced by methotrexate (MTX) have been examined. Materials and methods: A total of 24 male rats were divided into the following three groups: control group, MTX group, and MTX?+?QE group. Rats in MTX group received 20?mg/kg of single dose of MTX, while those in MTX?+?QE group received 20?mg/kg of single dose MTX, in addition to 15?mg/kg of QE administered 30?min prior to MTX and in the following 5-day period as a single daily dose. At the end of the experimental period, renal tissues were removed for histopathological and biochemical assessments. Results: Light microscopic examination showed a disruption of the renal structure in rats in MTX group in the form of tubular degeneration and dilation, with shedding of the tubular epithelial cells into the lumen. QE treatment was associated with less marked degenerative changes, with a similar histological appearance to that of controls. Furthermore, QE treatment resulted in decreased the number of apoptotic cells. Biochemical assessments showed significantly higher malondialdehyde (MDA) levels in MTX group as compared to control and MTX?+?QE groups. superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels showed a significant decrease in MTX group as compared to controls. However, QE significantly suppressed MDA level, compensated deficits in the anti-oxidant defenses [reduced SOD, GSH-Px, and CAT levels] in kidney tissue resulted from MTX administration. Conclusions: In conclusion, renal toxic effects of MTX may be alleviated by QE.     

Trehalose attenuates spinal cord injury through the regulation of oxidative stress,inflammation and GFAP expression in rats

Objective: Inflammation and oxidative stress are implicated in pathogenesis of spinal cord injury (SCI). Trehalose, a nonreducing disaccharide, exhibits anti-inflammatory and antioxidant effects. The present study investigated the therapeutic efficacy of trehalose in the SCI model.

Design and setting: An experimental study was designed using 120 male Wistar rats which were randomly divided into three groups including SCI, SCI?+?phosphate buffer saline (vehicle) and SCI?+?trehalose. All rats were subjected to SCI. Immediately after SCI, vehicle and trehalose groups received intrathecal injection of buffer and trehalose, respectively.

Outcome measures: The level of tissue TNFα, IL-1β, nitric oxide, malondialdehyde, myeloperoxidase, glial fibrillary acidic protein (GFAP) as well as hindlimb function were assessed at 4 hours, 1, 3 and 7 days post-SCI.

Results: Data indicated an early significant decrease in inflammatory and oxidative responses following SCI in trehalose treated group. Moreover, trehalose reduced GFAP expression as soon as 1-day post-trauma. Furthermore, trehalose treatment increased the score of hindlimb function.

Conclusion: Our results indicated that treatment with trehalose reduces the development of secondary injury associated with SCI. This effect likely underlies improved neurological function.     

Beneficial Effects of N-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Abstract

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague–Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.