Nephroprotective effect of date fruit extract against dichloroacetic acid exposure in adult rats

The aim of this study was to investigate the protective effects of aqueous date extract (ADE) on dichloroacetic acid (DCA)-induced nephrotoxicity. In vitro, total phenolic content estimated in the ADE were 417.71 mg gallic acid equivalents/100 g fresh weights (FW), while total flavonoid and tannins contents were 285.23 and 73.65 mg catechin equivalents/100 g FW, respectively. The ADE has strong scavenging activity. Ferulic, caffeic and p-coumaric acids are the major’s compounds. Nephrotoxicity was induced in male Wistar rats by the administration of 0.5 and 2 g/L DCA as drinking water. Some of these rats received also by gavage ADE (4 mL/kg) before the administration of DCA. After two months of experiment, DCA administration caused elevated levels of renal MDA, significant depletion of GSH levels, altered the antioxidant enzyme activities and deteriorated the renal functions as assessed by the increased plasma urea, uric acid and creatinine levels compared to control rats. The treatment with the ADE significantly normalized the increased plasma levels of creatinine, urea and uric acid, reduced the elevated MDA levels, significantly normalized the antioxidant enzyme activities and GSH level and restored the altered kidney histology in rats treated with DCA. Therefore, it was speculated that ADE protects rats from kidney damage through its antioxidant capacity.     

Steroid withdrawal and reduction of cyclosporine A under mycophenolate mofetil after heart transplantation

Survival and quality of life after heart transplantation are limited by a significant incidence of cardiovascular complications. Side effects of immunosuppressives contribute unfavorably. Aim of this study was to determine (1) whether withdrawal of corticosteroids and dose reduction of cyclosporine A can be performed safely under immunosuppressive therapy with mycophenolate mofetil and (2) if this is beneficial for renal function and cardiovascular risk reduction. Long term heart transplant recipients on steroids and cyclosporine A were examined in a monocentric, prospective, single-arm cohort study. Steroids were withdrawn, mycophenolate mofetil introduced and cyclosporine A dose reduced (target level 50–90 ng/ml). Follow up was 24 months. 23 patients were analyzed: Renal parameters (creatinine, urea, uric acid) improved significantly (p < 0.01), as did cardiovascular parameters (heart rate [p < 0.05], systolic and diastolic blood pressure [p < 0.01]), HbA1c (p < 0.05) and triglycerides (p < 0.05). In contrast, the self-percepted state of health (SF36?) decreased. Drop outs occurred mostly due to steroid withdrawal syndrome [n = 7]. The incidence of adverse events reflected the usual course after heart transplantation. We conclude that CS free immunosuppression comprising reduced cyclosporine levels and addition of MMF in long term heart transplant recipients is safe and improves the cardiovascular risk profile, carbohydrate metabolism and renal function.     

Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: Role of oxidative stress and caspase-3

Cadmium (Cd) is an environmental and industrial pollutant that can induce a broad spectrum of toxicological effects that affect various organs in humans and experimental animals. This study aims to investigate the effect of betaine supplementation on cadmium-induced oxidative impairment in rat kidney. The animals were divided into four groups (n = 10 per group): control, cadmium, betaine and betaine + cadmium (1) saline control group; (2) cadmium group in which cadmium chloride (CdCl₂) was given orally at a daily dose of 5 mg/kg body weight for four weeks; (3) betaine group, in which betaine was given to rats at a dose of 250 mg/kg/day, orally via gavage for six weeks; (4) cadmium + betaine group in which betaine was given at a dose of 250 mg/kg/day, orally via gavage for two weeks prior to cadmium administration and concurrently during cadmium administration for four weeks. Cadmium nephrotoxicity was indicated by elevated blood urea nitrogen (BUN) and serum creatinine levels. Kidneys from cadmium-treated rats showed an increase in lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) concentration and reductions in total antioxidant status (TAS), reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase concentration (SOD) and catalase activity. Caspase-3 activity, a marker of DNA damage was also elevated in renal tissues of cadmium-treated rats. Pre-treatment of rats with betaine substantially attenuated the increase in BUN and serum creatinine levels. Betaine also inhibited the increase in TBARS concentration and reversed the cadmium-induced depletion in total antioxidant status, GSH, GSH-Px, SOD and catalase concentrations in renal tissues. Renal caspase-3 activity was also reduced with betaine supplementation. These data emphasize the importance of oxidative stress and caspase signaling cascade in cadmium nephrotoxicity and suggest that betaine pretreatment reduces severity of cadmium nephrotoxicity probably via antioxidant action and suppression of apoptosis.     

Effect of repeated administration of 4-methylpyrazole on renal function and lipid peroxidation products in rat kidney after ethylene glycol poisoning

Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15 mg/kg b.w. after 2 h, followed by 10 mg/kg b.w. every 12 h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney’s lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745 mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys.     

Urinary CD20 mRNA as a surrogate of CD20-positive cells infiltration during allograft dysfunction in renal transplant patients

B lymphocyte infiltration in renal acute allograft rejection has been associated with steroid resistance and poor outcomes. We aimed to measure CD20 mRNA in urine of renal transplant patients with graft dysfunction and correlate with the histological diagnosis and immunohistochemical (IH) staining for CD20. A total of 48 urine samples were analyzed (21 with acute rejection, 10 with chronic allograft nephropathy, 11 with unspecific tubular lesions, 3 with acute pyelonephritis and 3 with polyomavirus nephropathy). Higher urinary CD20 levels associated with a positive IH staining for CD20 (> 50 positive cells/HPF) in renal tissue (p = 0.04), with a sensitivity of 83.3% and a specificity of 51.6%. Within the acute rejection group, a positive staining for CD20 was not associated with graft loss, steroid resistance or lack of return to basal creatinine after treatment, but was associated with higher serum creatinine at 3 and 6 months, 1 and 2 years after the acute episode (p < 0.05). In conclusion, we showed that urinary levels of CD20 detected by RT-PCR had a high sensitivity for CD20+ staining in the corresponding renal tissue, but with a low specificity. Patients with clusters of CD20+ cells > 50/HPF had higher serum creatinine after 2 years of follow up.     

Prevention of CCl4-induced nephrotoxicity with Sonchus asper in rat

Sonchus asper (SA) is locally used in renal aliments. The present work investigated the antioxidant effects of S. asper methanolic extract (SAME) against CCl₄-induced nephrotoxicity in Sprague–Dawley male rats. CCl₄ (3 ml/kg b.w., i.p.; 30% in olive oil) biweekly for 4 weeks induced lipid peroxidation, as reflected by significant increase of TBARS; diminished the renal antioxidant defenses, as revealed by a decrease of the level of GSH, CAT, SOD, GST, GSR, GSH-Px and QR while elevated the level of γ-GT, H₂O₂ and nitrite contents. CCl₄ caused histopathological injuries and significantly increased the renal AgNORs count and DNA damage. Telomerase activity in kidney was determined positive with CCl₄ treatment. Creatinine, urobilinogen and urea concentration was increased whereas creatinine clearance was decreased in serum and urine. Level of protein and albumin was increased in urine while reduced in serum. Serum level of nitrite was increased with CCl₄ treatment. Treatment of rats with SAME (100, 200 mg/kg b.w.) effectively ameliorated the alterations induced with CCl₄ in lipid peroxidation, antioxidant defenses, biochemical markers, genotoxicity and renal lesions. The present data suggests that SAME protect the kidneys possibly by alleviating the oxidative stress induced with CCl₄ in rat.     

Pioglitazone ameliorates methotrexate-induced renal endothelial dysfunction via amending detrimental changes in some antioxidant parameters,systemic cytokines and Fas production

Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 days) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01–2.43 nmol) and isoprenaline (1 μmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting 2 days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001–10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.     

Protective effect of dietary flaxseed oil on arsenic-induced nephrotoxicity and oxidative damage in rat kidney

Arsenic, a naturally occurring metalloid, is capable of causing acute renal failure as well as chronic renal insufficiency. Arsenic is known to exert its toxicity through oxidative stress by generating reactive oxygen species (ROS). Flaxseed, richest plant based dietary source of ω-3 polyunsaturated fatty acids (PUFAs) and lignans have shown numerous health benefits. Present study investigates the protective effect of flaxseed oil (FXO) on sodium arsenate (NaAs) induced renal damage. Rats prefed with experimental diets (Normal/FXO diet) for 14 days, were administered NaAs (20 mg/kg body weight i.p.) once daily for 4 days while still on the experimental diets. NaAs nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. Administration of NaAs led to a significant decline in the specific activities of brush border membrane (BBM) enzymes both in kidney tissue homogenates and in the isolated membrane vesicles. Lipid peroxidation and total sulfhydryl groups were altered upon NaAs treatment, indicating the generation of oxidative stress. NaAs also decreased the activities of metabolic enzymes and antioxidant defence system. Histopathological studies supported the biochemical findings showing extensive damage to the kidney by NaAs. In contrast, dietary supplementation of FXO prior to and alongwith NaAs treatment significantly attenuated the NaAs-induced changes.     

Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats

The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4 mg/kg bw/day), ChlA (5 mg/kg bw/day) or the combination OTA (0.4 mg/kg bw/day) + ChlA (5 mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA + ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism.     

Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats

Oxidative stress and apoptotic cell death in kidney have been suggested as contributing factors in the development and complication of diabetes especially in diabetic nephropathy (DN). This study investigated the effects of trigonelline (TG) on the renal functional, morphological changes and renal apoptosis in neonatal diabetic rats, a model of non-insulin-dependent diabetes mellitus. Diabetes mellitus was induced in one day old neonatal Wistar rat pups by an intraperitoneal (i.p.) injection of streptozotocin (STZ) (50 mg/kg) and monitored for 16 weeks thereafter. The diabetic rats were divided as follows: the nSTZ diabetic group, the TG (50 mg/kg) treated diabetic group, and the TG (100 mg/kg) treated diabetic group. The age matched nondiabetic group received an injection of citrate buffer (0.1 M, pH 4.5). At the end kidney samples were taken for light microscopic examinations. The levels of serum creatinine and BUN were significantly low in TG (100 mg/kg) treated diabetic rats. Glomerular filtration rate was improved in TG treated rats. The activities of antioxidant enzyme and membrane bound enzyme were decreased and the levels of tumor necrotic factor (TNF-α) and hydroxyproline content were increased in renal tissues of the diabetic group. TG (100 mg/kg/day) treatment for a period of 4 weeks showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. The degenerative changes in kidney tissue and fibrosis were alleviated in the TG treated groups. These results suggested that TG might have a significant role in alleviating kidney damage in nSTZ-diabetic rats.     

Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress,inflammation, autophagy and apoptosis

The aim of this study was to investigate the therapeutic activity of isoquinoline alkaloid berberine against cisplatin (CP)-induced nephrotoxicity in mice. Berberine was administered at daily doses of 1, 2 and 3 mg/kg by gavage for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Mice were sacrificed 24 h after the last dose of berberine. Histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP were significantly ameliorated by berberine in a dose-dependent manner. Additionally, oxidative/nitrosative stress, evidenced by the increase in renal 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced. The expression of nuclear factor-kappaB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was markedly suppressed by berberine, indicating the inhibition of inflammatory response. Treatment of CP-intoxicated animals with berberine also significantly reduced the expression of p53, active caspase-3 as well as autophagy marker light chain 3B (LC3B) in the kidneys. The results of the current study showed the nephroprotective activity of berberine against CP-induced renal injury, which could be attributed to the inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.     

Ulinastatin inhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor β (TGF-β)/Smad signalling pathways

This study aims to explore the protective effects and mechanisms of ulinastatin (UTI), which is a urinary trypsin inhibitor, of the renal interstitial fibrosis of rats subjected to unilateral ureteral obstruction (UUO). A total of 36 male Wistar rats were divided in random into three groups, namely, the sham operation (SOR) group (n = 12), the UUO group (n = 12), and the UTI treatment group (n = 12). Six rats from each group were euthanised after unilateral ureteral obstruction operation on the seventh and fourteenth days, respectively. Blood samples were harvested for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement. The interstitial pathological changes of the tissue from the obstructed kidneys were observed using haematoxylin–eosin (H&E) and Masson staining. The expression of the transforming growth factor β type 1 (TGF-β1), α-smooth muscle actin (α-SMA), type I collagen (Col-I), and phosphorylated Smad2/3 (p-Smad2/3) was determined using immunohistochemistry. The protein expression levels of TGF-β1, α-SMA, and p-Smad2/3 were examined using Western blot analysis. The results show that ulinastatin has no statistically significant effect on the BUN and Scr levels (P > 0.05), but it can significantly reduce renal interstitial injury and suppress interstitial collagen deposits. The renoprotective effect of ulinastatin is likely realised through the TGF-β/Smad signalling pathways.     

Cadmium induced pathophysiology: Prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement

The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves (AECO) against CdCl₂ intoxication. In vitro bioassay on isolated mice hepatocytes confirmed dose dependent cytoprotective effect of AECO. The CdCl₂ (30 μM) exhibited a significantly increased levels of lipid peroxidation, protein carbonylation along with the reduction of antioxidant enzymes and reduced glutathione levels in hepatocytes. AECO (200 and 400 μg/ml) + CdCl₂ (30 μM) could significantly restore the aforementioned oxidation parameters in hepatocytes. Beside this, AECO could significantly reduce Cd-induced increase in Bad/Bcl-2 ratio and the over-expression of NF-κB, caspase 3 and caspase 9. In in vivo assay, CdCl₂ (4 mg/kg body weight, for 6 days) treated rats exhibited a significantly increased intracellular Cd accumulation, oxidative stress and DNA fragmentation in the organs. In addition, the haematological parameters were significantly altered in the CdCl₂ treated rats. Simultaneous administration of AECO (50 and 100 mg/kg body weight), could significantly restore the biochemical, antioxidant and haematological parameters near to the normal status. Histological studies of the organs supported the protective role of jute leaves. Presence of substantial quantity of phenolic compounds and flavonoids in extract may be responsible for overall protective effect.     

Ligustrazine attenuates elevated levels of indoxyl sulfate,kidney injury molecule-1 and clusterin in rats exposed to cadmium

In this study, we aimed at evaluating the effect of ligustrazine, a major constituent of Ligusticum wallichii from traditional Chinese medicine, on Cd-induced changes in nephrotoxicity indices. Rats were divided into four experimental groups: control; ligustrazine; Cd and ligustrazine + Cd. Cd treated alone group showed significant decreases (P < 0.05) in body weight, renal levels of superoxide dismutase (SOD) and glutathione reductase (GR); and significant increases (P < 0.05) in urine volume (24 h), pH values, serum blood urea nitrogen (BUN), serum uric acid, kidney malondialdehyde (MDA), urinary total protein, urinary glucose, urinary lactate dehydrogenase (LDH) and urinary alkaline phosphatase (ALP). Apart from indoxyl sulfate (a uremic toxin), two newly accepted nephrotoxicity biomarkers including kidney injury molecule-1 (kim-1) and clusterin were also found to be increased. Nonetheless, all these effects induced by Cd were reversed upon treatment by ligustrazine although it failed in decreasing the concentrations of Cd in kidney and urine. Histopathological studies in Cd-treated rats exhibited renal tubule damage, which was also ameliorated by ligustrazine pretreatment. These results suggest that ligustrazine exhibits protective effects on Cd-induced nephrotoxicity. Additionally, this study also demonstrates Cd exposure induces elevated levels of indoxyl sulfate in serum and kidney, and clusterin in urine.     

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12 h and 24 h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role.     

1,2-Diazole prevents cisplatin-induced nephrotoxicity in experimental rats

BackgroundCisplatin (a platinum-compound) is a anti-neoplastic drug used in the treatment of various cancers but eventually results in severe adverse effects namely nephrotoxicity or renal disorder through generation of reactive oxygen species (ROS). This biochemical measurements and histopathology analysis investigated a possible protective effect of 1,2-diazole with regards to cisplatin-induced nephrotoxicity in experimental animals.MethodsAnimals were divided into four groups of six mice each. Group A: normal control, vehicle (1 % (w/v) gum acacia in phosphate buffer saline (PBS)). Group B: cisplatin group, vehicle + cisplatin (7.5 mg/kg). Group C: 1,2-diazole (10 mg/kg) + cisplatin and Group D: silymarin (50 mg/kg) + cisplatin. Each vehicle/drug treatment was given daily via intraperitoneal (ip) injection for 10 consecutive days starting from day 1. On group B, C and D cisplatin was given in single dose only on day 5 one hour post drug administration. Animals were allowed till 10^th day and on day 11 all four groups animals were anesthetized. Blood samples were collected and serum was isolated for biochemical measurements. The rats were then euthanized by cervical dislocation and their kidney was recovered and then prepared for biochemical measurements and histopathology analyses.ResultsPretreatment with 1,2-diazole prevented nephrotoxicity induced by cisplatin through a protective mechanism that involved reduction of increased oxidative stress by significantly increasing the enzymatic and non enzymatic antioxidant enzymes such as glutathione peroxidase (GPx), glutathione (GSH) and diminishing the lipid peroxidation (LPO). The pretreatment with 1,2-diazole does not affect superoxide dismutase (SOD), catalase (CAT), serum urea and creatinine level during nephrotoxicity when compared to cisplatin-induced group. Moreover, the 1,2-diazole animals shown significant decrease in urine volume and kidney weight when compared with cisplatin-induced group. Histopathological findings reveals the protective efficacy of 1,2-diazole that restores histopathological changes against nephrotoxicity.ConclusionThese analysis will provide a critical evidence that 1,2-diazole could provide a new protective strategy against cisplatin-induced nephrotoxicity.     

The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats

Mercury (Hg) is the third most dangerous heavy metal after arsenic and lead. Mercury’s toxicity brings serious risks to health through negative pathological and biochemical effects. The study was designed to investigate the possible protective role of berberine (BN) in mercuric chloride (HgCl₂) induced oxidative stress in hepatic and renal tissues. Adult male albino Wistar rats were exposed to mercuric chloride (HgCl₂; 0.4 mg/kg bwt) for 7 days. Treatment with HgCl₂ induced oxidative stress by increasing lipid peroxidation and nitric oxide production along with a concomitant decrease in glutathione and various antioxidant enzymes, namely superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. HgCl₂ intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of urea and creatinine in serum. BN (100 mg/kg bwt) treatment inhibited lipid peroxidation and nitric oxide production, whereas it increased glutathione content. Activities of antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, were also restored concomitantly when compared to control after BN administration. BN also inhibited the apoptotic effect of HgCl₂ by increasing the expression of Bcl-2 protein in liver and kidney. Histopathological examination of the liver and kidney tissues proved the protective effect of BN against HgCl₂ toxicity. These results demonstrated that BN augments antioxidant defense against HgCl₂-induced toxicity and provides evidence that it has therapeutic potential as hepato- and reno-protective agent.     

Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model

ObjectiveWe evaluated the effect of astaxanthin (ASX) and vitamin E (vit E) on colistin methanesulfonate (CMS) induced-nephrotoxicity in rats.MethodsAnimals were treated with sterile saline, 300 000 or 450 000 IU/kg/day of CMS, CMS + ASX (20 mg/kg), CMS + vit E (100 mg/kg), or CMS + 1 ml/kg olive oil (OO) for 7 days. The plasma/urine creatinine (Cr) level, urine γ-glutamyl-transferase (GGT) level, and renal tissue activities in malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reductase (GSH), as well as renal histology were performed.ResultsCMS induced a tubular damage, increased the GGT and MDA levels, and decreased the activities of SOD, CAT, GPx and GSH. Co-treatment with ASX or vit E restored all biochemical parameters cited above and improved the histopathological damage.ConclusionNephrotoxicity induced by CMS might be due to oxidative damage. The improvement by ASX or vit E seems to be related to their antioxidant properties.     

Effect of Aerva lanata against hepatotoxicity of carbon tetrachloride in rats

The partially purified petroleum ether extractable fraction of the whole plant Aerva lanata (PF) was evaluated for the protective effect against liver damage induced by carbon tetra chloride (CCl₄) in Sprague Dawley rats. Rats were orally administered with PF (50 and 100 mg/kg body weight) for 14 days before CCl₄ challenge and 100 mg of PF alone for toxicity analysis without CCl₄ administration. The results showed that CCl₄ administration significantly damaged the liver as evident from histopathology and very high activity of serum and liver marker enzymes. It also reduced the antioxidant enzyme status of the animals. PF administration significantly reversed the histopathological changes and restored the elevated activities of liver marker enzymes and also enhanced the antioxidant enzyme activities. The extract also reduced hepatic lipid peroxidation and increased the serum total protein and albumin/globulin (A/G) ratio. Preliminary phytochemical analysis of PF showed the presence of alkaloids. These observations clearly indicate that PF contains antioxidant alkaloids capable of ameliorating the CCl₄-induced hepatic injury by virtue of its antioxidant activity.     

Therapeutic effect of carnosine in rat model of experimental liver carcinogenesis

The possible anticancer effect of carnosine versus doxorubicin was investigated against hepatocellular carcinoma (HCC) induced by trichloroacetic acid (TCA) (500 mg/kg/day, p.o., for 5 days) in rats. Following induction of HCC, rats treated with either carnosine (10 mg/kg/day, i.p.), or doxorubicin (2.5 mg/kg, i.p., once weekly), for 2 weeks. Carnosine significantly decreased serum alanine aminotransferase, and hepatic lipid peroxidation, nitric oxide, tumor necrosis factor-α, and nuclear factor-κB p65 unit, and significantly increased liver total antioxidant status in TCA-challenged rats. The effects of doxorubicin on oxidative, nitrative, and inflammatory biomarkers were less significant than carnosine. However, both carnosine and doxorubicin significantly induced liver tissue apoptotic biomarkers, Bax, cytosolic cytochrome C, and caspase-3, in a comparable manner. Additionally, carnosine and doxorubicin reduced the histopathological dysplastic changes, and alpha-fetoprotein expression in liver of rats with HCC. It was concluded that carnosine significantly protected against TCA-induced liver carcinogenesis in rats, through its antioxidant, antinitrative, and anti-inflammatory effects, and induction of apoptosis.