Kidney Tissue Malondialdehyde Research Articles

Ameliorative effects of <i>Cnestis ferruginea</i> root extract on carbon tetrachloride nephrotoxicity in albino Wistar rats

The objective of this research was to assess the potential protective properties of ethanol extract derived from Cnestis ferruginea against the toxic effects by carbon tetrachloride (CCl4) in the kidneys of rats. In this study, male albino Wistar rats were pre-treated with C. ferruginea at doses of 100 and 200 mg/kg body weight (b.w.) on a daily basis for a duration of 14 days. Subsequently, a single dosage of CCl4 was administered intraperitoneally on the 7th day of the experiment. The rats were euthanized 24 hours after they were subjected to treatments using the extract on the 15th day. Subsequently, serum and kidneys were obtained and utilized for the analysis of biochemical parameters. Rats grouped as the control which were administered CCl4 experienced kidney damage, as indicated by a statistically significant increase (P < 0.05) in the measured parameters (urea, creatinine, uric acid in serum and malondialdehyde in kidney tissue), and a significant reduction in the levels of oxidative stress marker enzymes (superoxide dismutase, catalase and glutathione peroxidase). It is worth noting that the administration of C. ferruginea to rats exposed to CCl4 resulted in a significant reversal of the aforementioned changes, bringing them closer to a state of normalcy. The result obtained from this study suggest that C. ferruginea possess therapeutic properties which could protect the kidney against renal deterioration and its associated dysfunction.

Renal injury induced by cadmium chloride and the protective effect of vitamin C in mice

To investigate the renal injury induced by cadmium chloride(CdCl_2) and the protective effect of vitamin C(VC) in mice. Forty healthy clean grade male Kunming mice were randomly divided into 4 groups: control group(double distilled water gavage and intraperitoneal injection), VC group(200 mg/kg VC gavage and double distilled water intraperitoneal injection), CdCl_2 group(double distilled water gavage and 2 mg/kg CdCl_2 intraperitoneal injection), VC+CdCl_(2 )group(200 mg/kg VC gavage and 2 mg/kg CdCl_2 intraperitoneal injection). Exposure for 30 days.24 hours after the last exposure, the eyeballs were taken out for blood, and the renal tissue was immediately taken out to calculate kidney coefficient and then separate renal cells. The levels of reactive oxygen species(ROS) were detected by DCFH-DA kit and flow cytometry. Blood urea nitrogen(BUN), serum creatinine(Scr)and β2 microglobulin(β2-MG), cystatin C(Cys C), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), malondialdehyde(MDA), Caspase3 and Caspase9 kits were used to detect the corresponding indicators respectively. The contents of Cd~(2+) and Zn~(2+) in serum and kidney were detected by graphite furnace atomic absorption spectrometry. The levels of kidney coefficient and BUN, Scr, β2-MG were 1.36±0.10, (19.34±0.63)mmol/L, (61.30±2.04)mmol/L and(1.02±0.10)g/mL respectively in CdCl_(2 )group, which were higher than those in the control group and VC group(P<0.05). The levels of the above four indexes in VC+CdCl_(2 )group were 1.09±0.10, (9.65±0.50)mmol/L, (41.85±1.27)mmol/L and(0.61±0.01)g/mL respectively, which were lower than those in CdCl_2 group(P<0.05). CdCl_2 exposure resulted in unclear glomerular contour, swelling of renal tubules, interstitial hyperemia, and exfoliated epithelial cells in the lumen. VC pretreatment could improve the above changes. The levels of Cd~(2+) in serum and renal tissue of mice in CdCl_2 group were(4.36±0.07)μg/L, (18.6±1.95)μg/g respectively, which were higher than that of control group and VC group(P<0.05), in VC+CdCl_2 group, the level were(2.12±0.06)μg/L and(2.18±0.09)μg/g, they were lower than that of CdCl_2 group(P<0.05). The level of serum Zn~(2+ )in CdCl_2 group was(11.35±1.03)μg/L, that was lower than control group(P<0.05). The level of serum Zn~(2+) in VC+CdCl_2 group was(26.98±3.13)μg/L, which was higher than that of CdCl_2 group(P<0.05). The levels of ROS, MDA, Caspase3 and Caspase9 in kidney tissue of mice in CdCl_2 group were(1.86±0.13), (4.78±0.15)nmol/mg, 1.50±0.24 and 1.69±0.17 respectively, which were higher than those in control group(P<0.05). And the level of GSH-Px was(261.3±23.36)U/mg, it was lower than that in control group(P<0.05). Compared with the CdCl_2 group, the levels of ROS, MDA, Caspase3 and Caspase9 in VC+CdCl_2 group decreased, and the level of GSH-Px increased, the difference was statistically significant(P<0.05). CdCl_2 exposure can lead to oxidative stress, damage of glomerulus and renal tubules, imbalance of zinc ion homeostasis, and damage of renal function. VC pretreatment can reduce the damage caused by CdCl_2 to a certain extent.

Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice

It's crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

Effect DEHP plasticizer on MDA concentration and histopathological changes in Contronix contronix japonica

In this experiment, we aimed to recorded the effect of chronic oral exposure to DEHP on lipid peroxidation and histopathological lesions induced in different organs. A total of 150 quail chick divided into two groups (75 quail’s chicks at each group), control group left without any treatment all time, the second group was orally administrated 5% of DEHP (278.05 mg/kg bw) three times per week and lasted for 60 days. At 30 and 60 days old, a total number of 25 from both groups were euthanized. Blood samples were collected to determine the serum concentration of DEHP and mono ethyl hexyl phthalate (MEHP), liver and kidney to estimate tissue concentration of malondialdehyde (MDA), samples from different organs for histopathological examination. The result showed that the concentration of DEHP and MEHP in blood's serum and concentration of MDA in liver and kidney significantly increased with time in comparison with the control group; besides, oral administration of DEHP induced sever pathological lesions, in brain, aorta, intestines, liver, lung, ovary and testis. In conclusion, the DEHP and its metabolic product MEHP significantly increased in serum and cause significant increase in concertation of MDA in liver and kidney tissues, produces a significant histopathological change in brain, aorta, liver, intestine, lung, ovary and testis that can cause a life-threatening condition.

Biochanin-A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF-β1 and PAR-2 genes expression in kidney tissues of STZ-induced diabetic rats.

One of the major complications of diabetes is diabetic nephropathy, and often many patients suffer from diabetic nephropathy. That is why it is important to find the mechanisms that cause nephropathy and its treatment. This study was designed to examine the antidiabetic effects of biochanin A (BCA) and evaluate its effects on oxidative stress markers and the expression of transforming growth factor-β1 (TGF-β1) and protease-activated receptors-2 (PAR-2) genes in the kidney of type 1 diabetic rats. After induction of diabetes using streptozotocin (STZ), 55 mg/kg bw dose, rats were randomly divided into four groups with six rats in each group as follows: normal group: normal control receiving normal saline and a single dose of citrate buffer daily; diabetic control group: diabetic control receiving 0.5% dimethyl sulfoxide daily; diabetic+BCA (10 mg/kg) group: diabetic rats receiving biochanin A at a dose of 10 mg/kg bw daily; diabetic+BCA (15 mg/kg) group: diabetic rats receiving biochanin A at a dose of 15 mg/kg bw daily. TGF-β1 and PAR-2 gene expression was assessed by real-time. Spectrophotometric methods were used to measure biochemical factors: fast blood glucose (FBG), urea, creatinine, albumin, lipids profiles malondialdehyde (MDA), and superoxide dismutase (SOD). The course of treatment in this study was 42 days. The results showed that in the diabetic control group, FBG, serum urea, creatinine, expression of TGF-β1 and PAR-2 genes, and the levels of MDA in kidney tissue significantly increased and SOD activity in kidney tissue and serum albumin significantly decreased compared to the normal group (p < 0.001). The results showed that administration of biochanin A (10 and 15 mg/kg) after 42 days significantly reduced the expression of TGF-β1 and PAR-2 genes and FBG, urea, creatinine in serum compared to the diabetic control group (p < 0.001), also significantly increased serum albumin compared to the diabetic control group (p < 0.001). The level of MDA and SOD activity in the tissues of diabetic rats that used biochanin A (10 and 15 mg/kg) was significantly reduced and increased, respectively, compared to the diabetic control group (p < 0.001). Also, the result showed that in the diabetic control group lipids profiles significantly is disturbed compared to the normal group (p < 0.001), the results also showed that biochanin A (10 and 15 mg/kg) administration could significantly improved the lipids profile compared to the control diabetic group (p < 0.001). It is noteworthy that it was found that the beneficial effects of the biochanin A were dose dependent. In conclusion, administration of biochanin A for 42 days has beneficial effect and improves diabetes and nephropathy in diabetic rats. So probably biochanin A can be used as an adjunct therapy in the treatment of diabetes.

Protective Effects of Hydroalcoholic Extract of Rosa canina Fruit on Vancomycin-Induced Nephrotoxicity in Rats.

Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5–35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group (P < 0.05). Based on histopathological analysis, RC extract at the dose of 500 mg/kg inhibited the destructive effects of VAN on kidney tissues. GC-MS analysis indicated that the main compositions were found to be lactose (21.96%), 3-t-butyloxaziridine (20.91%), and 5-oxymethylfurfurole (16.75%). The results indicated that oral administration of RC was able to reduce VAN-induced nephrotoxicity in rats, possibly through antioxidant pathways.

Effect of Zhulian needle insertion by slow twirling technique on peroxidation and apoptosis of kidney tissue in aging rats

To observe the effect of Zhulian needle insertion by slow twirling technique on the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and apoptosis rate in kidney tissue of aging model rats and explore the potential mechanism of such needling technique. A total of 40 adult male SD rats were randomized into a blank control group, a model control group, a Zhulian needling technique group and a routine acupuncture group, 10 rats in each one. Except the blank control group, the sub-acute aging rat models were established by intraperitoneal injection with 10% D-galactose solution, 5 mL/kg in the rats of the other groups. In the Zhulian needling technique group and the routine acupuncture group, Zhulian needle insertion by slow twirling technique and the routine acupuncture technique were exerted at "Guanyuan" (CV 4) and "Zusanli" (ST 36) respectively. The needles were retained for 30 min, once a day, for 28 days totally. After intervention, the content of H2O2 in kidney tissue was detected by colorimetry, the content of MDA in kidney tissue was detected by thiobarbituric acid method and the apoptosis rate of kidney cells was detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling. Compared with the blank control group, the contents of H2O2 and MDA in kidney tissue and kidney cell apoptosis rate were all increased in the model control group (P<0.05). Compared with the model control group, the contents of H2O2 and MDA in kidney tissue and kidney cell apoptosis rate were all reduced in the Zhulian needling technique group and the routine acupuncture group (P<0.05), and these indexes in the Zhulian needling technique group were all lower than the routine acupuncture group (P<0.05). Zhulian needle insertion by slow twirling technique delays aging probably by regulating peroxidation and apoptosis.

Combination therapy of phosphatidylserine liposome with cyclosporine A improves nephrotoxicity and attenuates delayed-type hypersensitivity response

This study aimed to evaluate the antioxidant capacity of phosphatidylserine liposome (PS) against oxidative stress due to cyclosporine A (CsA) and concurrent administration of PS and CsA on the attenuation of immune response. The effect of oral PS was evaluated on biochemical and oxidative renal markers and histopathology of nephrotic rats receiving CsA. The effect of co-administration of PS with CsA was also assessed on DTH (delayed-type hypersensitivity) reaction of immunized rats. The cytokines production level of IL-2 (Interleukin-2) and IFN-γ (Interferon gamma) was measured in immunized rat's splenocytes. PS treatment significantly (P < 0.05) reduced Cr and BUN of serum and MDA (malondialdehyde) in kidney tissue, and increased SOD (superoxide dismutase) and CAT (Catalase) of kidney tissue in CsA-nephrotic rats. Histopathology data indicated significantly (P < 0.05) nephrotoxicity improvement after 25-day treatment with PS. Furthermore, CsA plus PS administration significantly reduced DTH response and cytokines production of IL-2 and IFN-γ in immunized rats. In conclusion, coadministration of CsA plus PS may overcome oxidative stress and improve the performance of organ transplantation or autoimmune therapy.

Ligusticum chuanxiong Effects on Oxidative Stress and Nrf2/HO-1 Signaling Using Nano-Magnetic Beads in Bleomycin-Induced Renal Fibrosis Rats

Ligusticum chuanxiong can relieve the degree of renal fibrosis. However, the specific mechanism of Ligusticum chuanxiong to improve renal fibrosis is not yet clear. A unilateral ureteral obstruction was used to construct a rat renal fibrosis model. The rats were treated with 20 mg/kg and 40 mg/kg of Ligusticum chuanxiong. Four weeks after treatment, blood was collected from the rats, and the rats were sacrificed. Blood urea nitrogen (BUN), serum creatinine (Scr), kidney tissue malondialdehyde (MDA), and superoxide dismutase (SOD) levels were detected. Hematoxylin–eosin staining was used to observe the pathological rat kidney changes. The renal tissue smooth muscle actin (α-SMA) was detected by immunohistochemistry. Nrf2 and HO-1 levels were determined by PCR using nano-magnetic beads. The results showed BUN, Scr, and MDA levels reduced, while SOD levels were elevated in Ligusticum chuanxiong-treated rats, compared to model rats (P &lt; 0.05). These effects were more dramatic in Ligusticum chuanxiong high dose (HD) rats compared to Ligusticum chuanxiong low dose (LD) rats. Additionally, Nrf2 and HO-1 levels were elevated in Ligusticum chuanxiong-treated rats (P &lt; 0.05). These effects were also more dramatic in HD rats compared to LD rats. These findings indicated that Ligusticum chuanxiong early administration can reduce renal fibrosis in rats by stimulating the Nrf2/HO-1 pathway.

The Effect of Zinc and Melatonin Supplementation on Lipid Peroxidation of Various Tissues of Rats with by DMBA-Induced Breast Cancer

The purpose of this study was to investigate the effects of zinc and melatonin administration on lipid peroxidation in various tissues in DMBA-induced breast cancer in female rats. A total of 42 recently weaned Wistar rats were divided into 5 groups in the study: Group 1 (Control), Group 2 (DMBA Control), Group 3 (DMBA+Zinc), Group 4 (DMBA+Melatonin), Group 5 (DMBA+Melatonin, and Zinc). MDA (malondialdehyde) and GSH (glutathione) levels were determined via the spectrophotometric method in the lung, liver, spleen, pancreas, and kidney tissue samples taken from experimental animals. The highest lung, liver, spleen, pancreas, and kidney tissue MDA levels were obtained in the DMBA-induced breast cancer group control group (G2) (p&lt;0.05). MDA levels in DMBA+Zinc (G3), DMBA+Melatonin (G4), and DMBA+Melatonin and Zinc (G5) were significantly lower than group 2 (p&lt;0.05). Similarly, lung, liver, spleen, pancreas, and kidney tissue GSH levels of DMBA+Zinc (G3), DMBA+Melatonin (G4), and DMBA+Melatonin and Zinc (G5) were significantly higher than that of Group 2 (p&lt;0.05). The findings of the study indicated that increased lung, liver, spleen, pancreas, and kidney damage in DMBA-induced breast cancer is suppressed with the supplementation of zinc, melatonin, and combined zinc and melatonin.

The Effect of Giving Dadih on Malondialdehyde Levels and Renal Interstitial Fibrosis at Aging Kidney

BACKGROUND: The increase in the elderly poses problems in the areas of health, since it can cause aging of the physiological function of organs. It also has an impact on kidney function, which will enhance the chronic kidney disease. One of the theory that causes aging process is the free radical theory, which that accumulation of free radicals is caused by depletion of antioxidants. Therefore, exogenous antioxidants are needed and in this study author use dadih. Dadih is fermented buffalo milk, indigenous from West Sumatera-Indonesia. Peptides found in fermented milk contained antioxidant that can stimulate the formation of endogenous antioxidants and diversification of dadiah increases its effect as antioxidant.&#x0D; AIM: This study aims to prove the effect of dadih antioxidants on malondialdehyde (MDA) levels of kidney tissue and renal interstitial fibrosis.&#x0D; MATERIALS AND METHODS: An experimental study with post-test only control group design conducted to observe effect of dadih to kidney aging of Rattus norvegicus in the Laboratory of Andalas University. It used 30 R. norvegicus which were divided into three groups. Group K was a positive control (did not get dadih), Group P1 was given dadih 4.5 g once a day, and Group P2 was given dadih 4.5 g twice a day for 42 days. After that, MDA levels of kidney tissue are examined using the thiobarbituric acid reactive substances examination technique and examination of renal interstitial fibrosis which is done by histopathology with Sirius-red staining. Data were analyzed using the normality test with Shapiro–Wilk.&#x0D; RESULTS: The results showed that dadih can reduce levels of MDA in kidney tissue, where its decrease very significant in Group P1 (given dadih once a day) and Group P2 (given dadih twice a day) compared to the Group K (control group) 0.97 ± 0.06 pg/ml to 0.75 ± 0.03 pg/ml (p &lt; 0.05). Group P1 and Group P2 can also reduce the renal interstitial fibrosis rank. Obtained a decrease in the average fibrosis rank from Group K to Group P1 and subsequently to Group P2 (p &lt; 0.05).&#x0D; CONCLUSION: This study concluded that dadih can reduce MDA levels in kidney tissue and reduce renal interstitial fibrosis rank on aging kidney.

Effect of L/N-type Calcium Channel Blocker (Cilnidipine) on Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats

Background: The sympathetic nervous system plays a major role in the renal function through the vasoactive system and the Renin-Angiotensin-Aldosterone System. Even though interest in the renal protective effects of sympathetic blocker has been increased, there are not much data to clarify this efficiency in nitric oxide deficient hypertensive rats. Aim and Objectives: To find out the effect of cilnidipine, L/N-type calcium channel blocker on oxidative stress of kidney in nitric oxide synthase (NOS) inhibited experimental hypertensive rats. Material and Methods: Male Albino Wistar rats (n-24) were randomly allocated into four groups: group 1, control received vehicle; group 2, received Cilnidipine; group 3, received NG-nitro-L-arginine methyl ester hydrochloride (L-NAME); group 4, received L-NAME C All drugs are given orally for 4 weeks. Blood pressure was measured before and after the intervention and twice during intervention for all the rats. On the 29th day, blood was collected and animals were sacrificed and kidneys were collected. Serum and kidney tissue malondialdehyde (MDA) levels are estimated. Results: The results demonstrate that there is a significant increase in Mean Arterial Pressure (MAP) in L-NAME treated rats compared to the control group. Treatment with cilnidipine significantly decreases the MAP in group 4 rats. We also demonstrated the significantly elevated serum and kidney tissue MDA levels in L-NAME treated rat. Treatment with Cilnidipine reduced serum and kidney tissue MDA levels in group 4 rats compared to group 3 rats. Conclusion: The results demonstrate that cilnidipine has suppressive effects against progressive renal injury as evidenced by decreased oxidative stress indicator MDA levels in NO deficient hypertensive rats. This effect is explained by the L/N type calcium channel inhibition of cilnidipine, the L-type calcium channel blocking action lowers blood pressure and N-type calcium channel blocking action leads to suppression of the sympathetic nerve activity and renin-angiotensin-aldosterone system.

Does curcumin or metformin attenuate oxidative stress and diabetic nephropathy in rats?

Background: Since the importance of oxidative stress in the development of diabetic nephropathy (DN) has previously been established, the therapeutic effects of various natural antioxidant agents or synthetic drugs have so far been investigated. Objectives: The aim of this study was to investigate the beneficial effects of curcumin (a natural polyphenol) and metformin (a common therapeutic medicine for type 2 diabetes) on oxidative status in kidney of type 1 diabetic rats. Materials and Methods: In this experimental study 60 male Wistar rats were divided into 10 groups. Type 1 diabetes was induced by streptozotocin. Rats received chow diet and treated with either normal saline in control (N) and diabetic control (D) groups or different doses of metformin (Met) (300 or 500 mg/kg body weight) or curcumin (Cur) (50 or 150 mg/kg body weight) in N+Met300, N+Met500, N+Cur50, N+Cur150, D+Met300, D+Met500, D+Cur50, and D+Cur150 groups. Urinary creatinine, urea, and protein were measured. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were assessed in kidney tissues. Results: Both metformin and curcumin showed significant effects on urinary creatinine, urea, and protein levels (P value for all was &lt;0.001). Unlike metformin, curcumin completely restored TAC and TOS (P&lt;0.001), and MDA (P=0.012) in kidney tissues and significantly recovered the activities of SOD (P= 0.003), GPx (P&lt; 0.001), and catalase (P=0.011). Conclusions: Curcumin was found more effective than metformin in attenuating oxidative status in DN.

Daphnetin protects against cisplatin-induced nephrotoxicity by inhibiting inflammatory and oxidative response

Daphnetin, one of the major bioactive components isolated from Daphne odora, has been reported to have anti-inflammatory and anti-oxidative effects. Inflammation and oxidative stress have been known to play critical roles in cisplatin-induced nephrotoxicity. The purpose of this study was to investigate the protective effects of daphnetin on cisplatin-induced nephrotoxicity. The levels of blood urea nitrogen (BUN) and creatinine, as well as the kidney reactive oxygen species (ROS), and malondialdehyde (MDA) activity were measured in this study. The expression of inflammatory cytokines TNF-α and IL-1β were measured by ELISA. The results showed that daphnetin protected against cisplatin-induced nephrotoxicity by attenuating kidney histological changes, serum BUN and creatinine. Furthermore, the expression of TNF-α and IL-1β, as well as ROS and MDA in kidney tissues were decreased by daphnetin. In addition, daphnetin dose-dependently inhibited cisplatin-induced NF-κB activation and up-regulated the expression of Nrf2 and HO-1. In conclusion, the results of this study suggested that daphnetin inhibited cisplatin-induced nephrotoxicity by inhibiting NF-κB and activating Nrf2 signaling pathways. Daphnetin might be a promising agent in the treatment of kidney injury.

The protective effect and mechanism of amitriptyline on sepsis-induced kidney injury

Objective To investigate the protective effect and the mechanism of amitriptyline on sepsis-induced kidney injury. Methods 48 male Sprague Dawley (SD) rats were randomly divided into six groups: sham group, sham + saline group, sham + amitriptyline group, sepsis group, sepsis + saline group, sepsis + amitriptyline group .Sepsis model was induced by cecal ligation and puncture (CLP). Sham group did not undergo CLP. Amitriptyline were injected subcutaneously to rats with amitriptyline 3 mg/kg before treatment for 10 d, 2 times /d, while the control group was injected with the same amount of normal saline. Blood sample was obtained to detect serum level of acid sphingomyelinase (ASMase), ceramide, blood urea nitrogen (BUN), creatinine and interleukin-1β. Malondialdehyde in kidney tissue was determined, and Kidney hematoxylin eosin (HE) staining was performed to observe pathologic change. Another 48 rats were randomly divided into four groups: sham group, sepsis group, sepsis + saline group, sepsis + amitriptyline group. The intervention to each group were same as above description. Rats of the four groups were observed for seven days to determine the survival rate. Results The survival rate of rats in sham group were 100%, the survival rate of the sepsis group and the sepsis + physiological saline group was less than 20%, while the survival rate of the sepsis + amitriptyline group was > 50%. The serum concentration of IL-1β, ceramide, BUN, SCr, the activity of ASMase and the level of malondialdehyde (MDA) in kidney tissue were respectively increased in sepsis group , sepsis + saline group and sepsis + amitriptyline group at the 4 time points were significantly higher than the sham groups (P<0.01), these indexes in sepsis plus amitriptyline group were significantly decreased compared to sepsis group (P<0.01). There was no pathologic change in sham group, sham + saline group and sham + amitriptyline group. In sepsis group and sepsis + saline group, general degeneration and necrosis of renal proximal tubular epithelial cells , marked dilatation of renal tubular capsular space, extensive infiltration of inflammatory cells and hemorrhage in renal interstitium were observed. These pathologic changes were obviously reduced in sepsis + amitriptyline group compared with sepsis group. Conclusions Amitriptyline can alleviate sepsis-induced kidney injury, through inhibiting the activity of ASMase and then restraining inflammatory response and oxidative stress in renal tissues. Key words: Sepsis/CO/DT; Kidney diseases/CO/DT; Amitriptyline/TU; Rats

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

The effect of hypericum perforatum on kidney ischemia/reperfusion damage

It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague–Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR + HP Group which was treated with 50 mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p < 0.05). In the I/R + HP group, the levels of MDA decreased at a significant level compared to the I/R group, while the SOD, CAT, and GSH-PX activity increased (p < 0.05). In histopathological examinations, it was observed that the tubular dilatation and epithelial desquamation regressed in the IR + HP Group when compared with the I/R Group. It has been shown with the histological and biochemical results in this study that HP is protective against acute renal I/R.

Neutrophil gelatinase-associated lipocalin attenuates injury in the rat cecal ligation and puncture model of sepsis via apoptosis inhibition.

The aim of this study was to investigate the effect of neutrophil gelatinase-associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)-induced sepsis and the possible mechanism. Thirty male Sprague-Dawley rats underwent CLP as sepsis models and were randomized into three groups including the sham-operated group (sham, n = 10), which only underwent a laparotomy; the sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological and immunohistochemical examination, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase-1 (HO)-1. The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive TUNEL staining, activated Caspase-3 and Bax, and kidney tissue MDA levels in the sepsis group were significantly increased compared with those in the sham-operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO-1 expression in sepsis + NGAL group were significantly higher than those in the sham-operated group and the sepsis group (P < 0.05). NGAL can attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the protective effect of NGAL was probably due to the inhibition of apoptosis and lipid peroxidation, and increased expression of HO-1.

Preventive effects of 5-hydroxy-1-methylhydantoin on paraquat-induced nephrotoxicity in rat

To investigate the protective effects of 5-hydroxy-1-methylhyantoin (HM ) on paraquat (PQ)-induced nephrotoxicity in rat and its possible mechanism. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into four groups: namely control, PQ, vitamin C and HMH groups, with 6 rats in each group. The rats in control group were given an injection of 2 mg/kg of normal saline intraperitoneally. The rats in PQ group were given an injection of 50 mg/kg of PQ intraperitoneally. The rats in vitamin C and HMH groups were given 1 mmol/kg of vitamin C or HMH through gastric tube right after PQ injection. The hydroxyl free radical scavenging ability of HMH and vitamin C was determined by Fenton method. Blood sample was collected after 24 hours of PQ treatment, then the animals were sacrificed and renal tissues were harvested. Blood urea nitrogen (BUN), serum creatinine (SCr), protein content of renal cortex, blood malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) activity were determined. Both vitamin C and HMH showed a very good ability to scavenge hydroxyl radicals, and the 50% inhibiting concentration (IC₅₀) was both 4.02 mg/mL. Compared with control group, serum BUN, SCr and MDA in renal tissue were significantly increased in PQ group, and the protein, GSH contents and SOD activity were significantly decreased [BUN (mmol/L): 40.80 ± 2.49 vs. 13.67 ± 1.58, SCr (μmol/L): 163.46 ± 8.67 vs. 51.80 ± 4.37, MDA (nmol/g): 7.51 ± 0.23 vs. 4.52 ± 0.33, protein (μmol/L): 0.94 ± 0.14 vs. 1.35 ± 0.10, GSH (mg/g): 1.08 ± 0.48 vs. 3.30 ± 0.44, SOD (kU/L): 70.74 ± 6.42 vs. 112.89 ± 8.72, all P < 0.01 ]. Compared with PQ group, serum BUN and SCr and MDA in kidney tissue in vitamin C and HMH groups were significantly decreased, and GSH content and SOD activity in kidney tissue were significantly elevated [BUN mmol/L): 22.64 ± 2.36, 18.71 ± 5.23 vs. 40.80 ± 2.49, SCr (μmol/L): 97.28 ± 4.81, 89.20 ± 6.72 vs. 163.46 ± 8.67, MDA (nmol/g): 4.67 ± 0.31, 4.21 ± 0.42 vs. 7.51 ± 0.23, GSH (mg/g): 1.78 ± 0.10, 1.86 ± 0.39 vs. 1.08 ± 0.48, SOD (kU/L): 98.69 ± 5.43, 103.76 ± 4.45 vs. 70.74 ± 6.42, all P < 0.01]. Compared with vitamin C group, HMH could significantly reduce SCr contents P < 0.05). There were no differences in reduction PQ-induced BUN, MDA content, and effect on GSH content and SOD activity between vitamin C group and HMH group (all P > 0.05). HMH can protect the kidney against PQ-induced nephrotoxicity, and the mechanism of which maybe attributed to its anti-oxidation property and ability to scavenge hydroxyl radical.

The effect of dexmedetomidine against oxidative and tubular damage induced by renal ischemia reperfusion in rats

Dexmedetomidine (dex) is a potent, highly selective and specific α2-adrenoreceptor agonist. This experimental study was designed to investigate protective and therapeutic effect of two different doses of dex, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Male Sprague−Dawley rats were divided into four groups, each including 10 animals: control group, ischemia-reperfusion (I/R) group; treated groups with 10 μg/kg of dex and 100 μg/kg of dex. After removing right kidney of the rats, the left kidney has performed ischemia during 40 min and reperfusion in the following 3 h. The histopathological findings, and also tissue superoxide dismutase (SOD) and catalase (CAT) enzyme activity, malondialdehyde (MDA), glutathione (GSH), serum blood urea nitrogen (BUN), creatinine (Cre) and tumor necrosis factor-alpha (TNF-α) levels were determined. In the I/R group, compared to the control group, levels of BUN, Cre and kidney tissue MDA have increased significantly, SOD, CAT enzyme activity and glutathione levels have decreased significantly. In the dex10 group, compared to the I/R group, levels of Cre and TNF-α have decreased significantly, while the SOD activity has increased significantly. In the dex100 group, compared to the I/R group, levels of BUN, Cre have decreased significantly, while the SOD activity has increased significantly. In the I/R group, there was also extensive tubular necrosis, glomerular damage in the histological evaluation. Dex ameliorated these histological damages in different amounts in two treatment groups. In this study, the protective effects of dex against renal I/R injury have been evaluated by two different amount of doses.